AU783703B2 - Corynebacterium glutamicum genes encoding stress, resistance and tolerance proteins - Google Patents

Corynebacterium glutamicum genes encoding stress, resistance and tolerance proteins Download PDF

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AU783703B2
AU783703B2 AU58369/00A AU5836900A AU783703B2 AU 783703 B2 AU783703 B2 AU 783703B2 AU 58369/00 A AU58369/00 A AU 58369/00A AU 5836900 A AU5836900 A AU 5836900A AU 783703 B2 AU783703 B2 AU 783703B2
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protein
nucleic acid
srt
gene
corynebacterium
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Gregor Haberhauer
Hyung-Joon Kim
Burkhard Kroger
Heung-Shick Lee
Markus Pompejus
Hartwig Schroder
Oskar Zelder
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Paik Kwang Industrial Co Ltd
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Description

WO 01/00804 PCT/IB00/00922 CORYNEBACTERIUM GLUTAMICUM GENES ENCODING STRESS, RESISTANCE AND TOLERANCE PROTEINS Related Applications This application claims priority to prior filed U.S. Provisional Patent Application Serial No. 60/141031, filed June 25, 1999, U.S. Provisional Patent Application Serial No. 60/142692, filed July 1, 1999, and also to U.S. Provisional Patent Application Serial No. 60/151214, filed August 27, 1999. This application also claims priority to German Patent Application No. 19930429.7, filed July 1, 1999, German Patent Application No.
19931413.6, filed July 8, 1999, German Patent Application No. 19931457.8, filed July 8, 1999, German Patent Application No. 19931541.8, filed July 8, 1999, German Patent Application No. 19932209.0, filed July 9, 1999, German Patent Application No.
19932230.9, filed July 9, 1999, German Patent Application No. 19932914.1, filed July 14, 1999, German Patent Application No. 19940764.9, filed August 27, 1999, and German Patent Application No. 19941382.7, filed August 31, 1999. The entire contents of all of the aforementioned applications are hereby expressly incorporated herein in their entirety by this reference.
Background of the Invention Certain products and by-products of naturally-occurring metabolic processes in cells have utility in a wide array of industries, including the food, feed, cosmetics, and pharmaceutical industries. These molecules, collectively termed 'fine chemicals', include organic acids, both proteinogenic and non-proteinogenic amino acids, nucleotides and nucleosides, lipids and fatty acids, diols, carbohydrates, aromatic compounds, vitamins and cofactors, and enzymes. Their production is most conveniently performed through large-scale culture of bacteria developed to produce and secrete large quantities of a particular desired molecule. One particularly useful organism for this purpose is Corynebacterium glutamicum, a gram positive, nonpathogenic bacterium. Through strain selection, a number of mutant strains have been developed which produce an array of desirable compounds. However, selection of strains improved for the production of a particular molecule is a time-consuming and difficult process.
WO 01/00804 PCT/IB00/00922 -2- Summary of the Invention The invention provides novel bacterial nucleic acid molecules which have a variety of uses. These uses include the identification of microorganisms which can be used to produce fine chemicals, the modulation of fine chemical production in C.
glutamicum or related bacteria, the typing or identification of C. glutamicum or related bacteria, as reference points for mapping the C. glutamicum genome, and as markers for transformation. These novel nucleic acid molecules encode proteins, referred to herein as stress, resistance and tolerance (SRT) proteins.
C. glutamicum is a gram positive, aerobic bacterium which is commonly used in industry for the large-scale production of a variety of fine chemicals, and also for the degradation of hydrocarbons (such as in petroleum spills) and for the oxidation of terpenoids. The SRT nucleic acid molecules of the invention, therefore, can be used to identify microorganisms which can be used to produce fine chemicals, by fermentation processes. Modulation of the expression of the SRT nucleic acids of the invention, or modification of the sequence of the SRT nucleic acid molecules of the invention, can be used to modulate the production of one or more fine chemicals from a microorganism to improve the yield or production of one or more fine chemicals from a Corynebacterium or Brevibacterium species).
The SRT nucleic acids of the invention may also be used to identify an organism as being Corynebacterium glutamicum or a close relative thereof, or to identify the presence of C. glutamicum or a relative thereof in a mixed population of microorganisms. The invention provides the nucleic acid sequences of a number of C.
glutamicum genes; by probing the extracted genomic DNA of a culture of a unique or mixed population of microorganisms under stringent conditions with a probe spanning a region of a C glutamicum gene which is unique to this organism, one can ascertain whether this organism is present. Although Corynebacterium glutamicum itself is nonpathogenic, it is related to species pathogenic in humans, such as Corynebacterium diphtheriae (the causative agent of diphtheria); the detection of such organisms is of significant clinical relevance.
The SRT nucleic acid molecules of the invention may also serve as reference points for mapping of the C. glutamicum genome, or of genomes of related organisms.
WO 01/00804 PCT/IB00/00922 -3- Similarly, these molecules, or variants or portions thereof, may serve as markers for genetically engineered Corynebacterium or Brevibacterium species.
The SRT proteins encoded by the novel nucleic acid molecules of the invention are capable of, for example, permitting C. glutamicum to survive in a setting which is either chemically or environmentally hazardous to this microorganism. Given the availability of cloning vectors for use in Corynebacterium glutamicum, such as those disclosed in Sinskey et al., U.S. Patent No. 4,649,119, and techniques for genetic manipulation of C glutamicum and the related Brevibacterium species lactofermentum) (Yoshihama et al, J. Bacteriol. 162: 591-597 (1985); Katsumata et al., J Bacteriol. 159: 306-311 (1984); and Santamaria et al., J. Gen. Microbiol. 130: 2237- 2246 (1984)), the nucleic acid molecules of the invention may be utilized in the genetic engineering of this organism to make it a better or more efficient producer of one or more fine chemicals, through the ability of these proteins to permit growth and multiplication of C. glutamicum (and also continuous production of one or more fine chemicals) under circumstances which would normally impede growth of the organism, such as those conditions frequently encountered during large-scale fermentative growth.
For example, by overexpressing or engineering a heat-shock induced protease molecule such that it is optimized in activity, one may increase the ability of the bacterium to degrade incorrectly folded proteins when the bacterium is challenged with high temperatures. By having fewer misfolded (and possibly misregulated or nonfunctional) proteins to interfere with normal reaction mechanisms in the cell, the cell is increased in its ability to function normally in such a culture, which should in turn provide increased viability. This overall increase in number of cells having greater viability and activity in the culture should also result in an increase in yield, production, and/or efficiency of production of one or more desired fine chemicals, due at least to the relatively greater number of cells producing these chemicals in the culture.
This invention provides novel SRT nucleic acid molecules which encode SRT proteins which are capable of, for example, permitting C. glutamicum to survive in a setting which is either chemically or environmentally hazardous to this microorganism.
Nucleic acid molecules encoding an SRT protein are referred to herein as SRT nucleic acid molecules. In a preferred embodiment, the SRT protein participates in metabolic pathways permitting C. glutamicum to survive in a setting which is either chemically or 12/10 '05 WED 12:02 FAX 61 2 9888 7600 WATERMARK 11004 4 environmentally hazardous to this microorganism. Examples of such proteins include those encoded by the genes set forth in Table 1, The following embodiments of the Invention, the subject of this application, are specifically disclosed herein: An isolated Corynebacterium glutamicum nucleic acid molecule comprising the nucleotide sequence set forth in SEQ ID NO;1, or a complement thereof.
An isolated nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2, or a complement thereof.
An isolated nucleic acid molecule which encodes a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2, or a complement thereof.
An isolated nucleic acid molecule comprising a nucleotide sequence 15 which is functionally equivalent, and at least 50% identical, to the entire nucleotide sequence set forth in SEQ ID NO:1, or a complement thereof.
An isolated nucleic acid molecule comprising a fragment of at least 15 contiguous nucleotides of the nucleotide sequence set forth in ee. 20 SEQ ID NO:1, or a complement thereof.
An isolated polypeptide comprising a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence set S.forth in SEQ ID NO:2.
An isolated polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence which is functionally equivalent, and at least 50% Identical, to the entire nucleotide sequence set forth in SEQ ID NO:1, wherein said polypeptide has lincomycine resistance protein activity.
An Isolated polypeptide comprising an amino acid sequence which is functionally equivalent, and at least 50% identical, to the entire amino acid sequence set forth in SEQ ID NO:2.
COMS ID No: SBMI-01718905 Received by IP Australia: Time 12:10 Date 2005-10-12 12/10 '05 WED 12:03 FAX 61 2 9888 7600 WATERMARK o00os 4a An isolated polypeptide comprising a fragment of a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2 wherein said polypeptide fragment maintains a biological activity of the polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2.
A host cell comprising a nucleic acid molecule comprising the nucleotide sequence set forth in SEQ ID NO:1, wherein the nucleic acid molecule is disrupted.
A host cell comprising a nucleic acid molecule comprising the nucleotide sequence set forth in SEQ ID NO:1, wherein the nucleic acid molecule comprises one or more nucleic acid modifications as compared to the nucleotide sequence set forth in SEQ ID NO:1.
A host cell comprising a nucleic acid molecule comprising the nucleotide sequence set forth in SEQ ID NO:1, wherein the 15 regulatory region of the nucleic acid molecule is modified relative to the wild-type regulatory region of the molecule.
Accordingly, one aspect of the invention pertains to isolated nucleic acid molecules cDNAs, DNAs, or RNAs) comprising a nucleotide sequence o. encoding an SRT protein or biologically active portions thereof, as well as nucleic oe: 20 acid fragments suitable as primers or hybridization probes for the detection or amplification of SRT-encoding nucleic acid DNA or mRNA). In particularly preferred embodiments, the isolated nucleic acid molecule comprises one of the nucleotide sequences set forth as the odd-numbered SEQ ID NOs in the Sequence Listing SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID or the coding region or a complement thereof of one of these nucleotide sequences. In other particularly preferred embodiments, the isolated nucleic acid molecule of the invention comprises a nucleotide sequence which hybridizes to or is at least about 50%, preferably at least about 60%, more preferably at least about 70%, 80% or 90%, and even more preferably at least about 95%, 96%, 97%, 98%, 99% or more homologous to a nucleotide sequence set forth as an odd-numbered SEQ ID NO in the Sequence Listing SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID or a portion thereof. In other preferred embodiments, the Isolated nucleic acid molecule encodes one of the amino acid COMS ID No: SBMI-01718905 Received by IP Australia: Time 12:10 Date 2005-10-12 12/10 '05 WED 12:03 FAX 61 2 9888 7600 WATERMARK 1006 4b sequences set forth as an even-numbered SEQ ID NO in the Sequence Listing SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID The preferred SRT proteins of the present invention also preferably possess at least one of the SRT activities described herein.
In another embodiment, the isolated nucleic acid molecule encodes a protein or portion thereof wherein the protein or portion thereof includes an amino acid sequence which is sufficiently homologous to an amino acid sequence of the invention a sequence having an even-numbered SEQ ID NO: in the Sequence Listing), sufficiently homologous to an amino acid sequence of the invention such that the protein or portion thereof maintains an SRT activity.
Preferably, the protein or portion thereof encoded by the nucleic acid molecule maintains the ability to increase the survival of C. glutamicum in a setting which is either chemically or environmentally hazardous to this microorganism. In one embodiment, the protein encoded by the nucleic acid molecule is at least about 15 50%, preferably at least about 60%, and more preferably at least about 80%, or 90% and most preferably at least about 95%, 96%, 97%, 98%, or 99% or o o *ooo COMS ID No: SBMI-01718905 Received by IP Australia: Time 12:10 Date 2005-10-12 WO 01/00804 PCT/IB00/00922 more homologous to an amino acid sequence of the invention an entire amino acid sequence selected from those having an even-numbered SEQ ID NO in the Sequence Listing). In another preferred embodiment, the protein is a full length C. glutamicum protein which is substantially homologous to an entire amino acid sequence of the invention (encoded by an open reading frame shown the corresponding odd-numbered SEQ ID NOs in the Sequence Listing SEQ ID NO:1, SEQ ID NO:3, SEQ ID SEQ ID In another preferred embodiment, the isolated nucleic acid molecule is derived from C. glutamicum and encodes a protein an SRT fusion protein) which includes a biologically active domain which is at least about 50% or more homologous to one of the amino acid sequences of the invention a sequence of one of the even-numbered SEQ ID NOs in the Sequence Listing) and has the ability to increase the survival of C.
glutamicum in a setting which is either chemically or environmentally hazardous to this microorganism, or possesses one or more of the activities set forth in Table I, and which also includes heterologous nucleic acid sequences encoding a heterologous polypeptide or regulatory regions.
In another embodiment, the isolated nucleic acid molecule is at least nuclcotides in length and hybridizes under stringent conditions to a nucleic acid molecule comprising a nucleotide sequence of the invention a sequence of an oddnumbered SEQ ID NO in the Sequence Listing). Preferably, the isolated nucleic acid molecule corresponds to a naturally-occurring nucleic acid molecule. More preferably, the isolated nucleic acid encodes a naturally-occurring C. glutamicum SRT protein, or a biologically active portion thereof.
Another aspect of the invention pertains to vectors, recombinant expression vectors, containing the nucleic acid molecules of the invention, and host cells into which such vectors have been introduced. In one embodiment, such a host cell is used to produce an SRT protein by culturing the host cell in a suitable medium. The SRT protein can be then isolated from the medium or the host cell.
Yet another aspect of the invention pertains to a genetically altered microorganism in which an SRT gene has been introduced or altered. In one embodiment, the genome of the microorganism has been altered by the introduction of a nucleic acid molecule of the invention encoding wild-type or mutated SRT sequence as WO 01/00804 PCT/IB00/00922 -6a transgene. In another embodiment, an endogenous SRT gene within the genome of the microorganism has been altered, functionally disrupted, by homologous recombination with an altered SRT gene. In another embodiment, an endogenous or introduced SRT gene in a microorganism has been altered by one or more point mutations, deletions, or inversions, but still encodes a functional SRT protein. In still another embodiment, one or more of the regulatory regions a promoter, repressor, or inducer) of a SRT gene in a microorganism has been altered by deletion, truncation, inversion, or point mutation) such that the expression of the SRT gene is modulated. In a preferred embodiment, the microorganism belongs to the genus Corynebacterium or Brevibacterium, with Corynebacterium glutamicum being particularly preferred. In a preferred embodiment, the microorganism is also utilized for the production of a desired compound, such as an amino acid, with lysine being particularly preferred.
In another aspect, the invention provides a method of identifying the presence or activity of Cornyebacterium diphtheriae in a subject. This method includes detection of one or more of the nucleic acid or amino acid sequences of the invention the sequences set forth in the Sequence Listing as SEQ ID NOs 1 through 304)) in a subject, thereby detecting the presence or activity of Corynebacterium diphtheriae in the subject.
Still another aspect of the invention pertains to an isolated SRT protein or a portion, a biologically active portion, thereof. In a preferred embodiment, the isolated SRT protein or portion thereof possesses the ability to increase the survival of C glutamicum in a setting which is either chemically or environmentally hazardous to this microorganism. In another preferred embodiment, the isolated SRT protein or portion thereof is sufficiently homologous to an amino acid sequence of the invention a sequence of an even-numbered SEQ ID NO: in the Sequence Listing) such that the protein or portion thereof maintains the ability to increase the survival of C.
glutamicum in a setting which is either chemically or environmentally hazardous to this microorganism.
The invention also provides an isolated preparation of an SRT protein. In preferred embodiments, the SRT protein comprises an amino acid sequence of the invention a sequence of an even-numbered SEQ ID NO: of the Sequence Listing).
In another preferred embodiment, the invention pertains to an isolated full length protein WO 01/00804 PCT/IB00/00922 -7which is substantially homologous to an entire amino acid sequence of the invention a sequence of an even-numbered SEQ ID NO: of the Sequence Listing) (encoded by an open reading frame set forth in a corresponding odd-numbered SEQ ID NO: of the Sequence Listing).). In yet another embodiment, the protein is at least about preferably at least about 60%, and more preferably at least about 70%, 80%, or and most preferably at least about 95%, 96%, 97%, 98%, or 99% or more homologous to an entire amino acid sequence of the invention a sequence of an even-numbered SEQ ID NO: of the Sequence Listing). In other embodiments, the isolated SRT protein comprises an amino acid sequence which is at least about 50% or more homologous to one of the amino acid sequences of the invention a sequence of an even-numbered SEQ ID NO: of the Sequence Listing) and is able to improve the survival rate of C glutamicum in a setting which is either chemically or environmentally hazardous to this microorganism, or has one or more of the activities set forth in Table 1.
Alternatively, the isolated SRT protein can comprise an amino acid sequence which is encoded by a nucleotide sequence which hybridizes, hybridizes under stringent conditions, or is at least about 50%, preferably at least about 60%, more preferably at least about 70%, 80%, or 90%, and even more preferably at least about 96%, 97%, or 99% or more homologousto a nucleotide sequence of one of the even-numbered SEQ ID NOs set forth in the Sequence Listing. It is also preferred that the preferred forms of SRT proteins also have one or more of the SRT bioactivities described herein.
The SRT polypeptide, or a biologically active portion thereof, can be operatively linked to a non-SRT polypeptide to form a fusion protein. In preferred embodiments, this fusion protein has an activity which differs from that of the SRT protein alone. In other preferred embodiments, this fusion protein results in increased yields, production, and/or efficiency of production of a desired fine chemical from C. glutamicum. In particularly preferred embodiments, integration of this fusion protein into a host cell modulates the production of a desired compound from the cell.
In another aspect, the invention provides methods for screening molecules which modulate the activity of an SRT protein, either by interacting with the protein itself or a substrate or binding partner of the SRT protein, or by modulating the transcription or translation of an SRT nucleic acid molecule of the invention.
WO 01/00804 PCT/IB00/00922 -8- Another aspect of the invention pertains to a method for producing a fine chemical. This method involves the culturing of a cell containing a vector directing the expression of an SRT nucleic acid molecule of the invention, such that a fine chemical is produced. In a preferred embodiment, this method further includes the step of obtaining a cell containing such a vector, in which a cell is transfected with a vector directing the expression of an SRT nucleic acid. In another preferred embodiment, this method further includes the step of recovering the fine chemical from the culture. In a particularly preferred embodiment, the cell is from the genus Corynebacterium or Brevibacterium, or is selected from those strains set forth in Table 3.
Another aspect of the invention pertains to methods for modulating production of a molecule from a microorganism. Such methods include contacting the cell with an agent which modulates SRT protein activity or SRT nucleic acid expression such that a cell associated activity is altered relative to this same activity in the absence of the agent. In a preferred embodiment, the cell is modulated in resistance to one or more toxic chemicals or in resistance to one or more environmental stresses, such that the yields or rate of production of a desired fine chemical by this microorganism is improved. The agent which modulates SRT protein activity can be an agent which stimulates SRT protein activity or SRT nucleic acid expression. Examples of agents which stimulate SRT protein activity or SRT nucleic acid expression include small molecules, active SRT proteins, and nucleic acids encoding SRT proteins that have been introduced into the cell. Examples of agents which inhibit SRT activity or expression include small molecules, and antisense SRT nucleic acid molecules.
Another aspect of the invention pertains to methods for modulating yields of a desired compound from a cell, involving the introduction of a wild-type or mutant SRT gene into a cell, either maintained on a separate plasmid or integrated into the genome of the host cell. If integrated into the genome, such integration can random, or it can take place by homologous recombination such that the native gene is replaced by the introduced copy, causing the production of the desired compound from the cell to be modulated. In a preferred embodiment, said yields are increased. In another preferred embodiment, said chemical is a fine chemical. In a particularly preferred embodiment, said fine chemical is an amino acid. In especially preferred embodiments, said amino acid is L-lysine.
WO 01/00804 PCT/IB00/00922 -9- Detailed Description of the Invention The present invention provides SRT nucleic acid and protein molecules which are involved in the survival ofC. glutamicum upon exposure of this microorganism to chemical or environmental hazards. The molecules of the invention may be utilized in the modulation of production of fine chemicals from microorganisms, since these SRT proteins provide a means for continued growth and multiplication of C. glutamicum in the presence of toxic chemicals or hazardous environmental conditions, such as may be encountered during large-scale fermentative growth. By increasing the growth rate or at least maintaining normal growth in the face of poor, if not toxic, conditions, one may increase the yield, production, and/or efficiency of production of one or more fine chemicals from such a culture, at least due to the relatively greater number of cells producing the fine chemical in the culture. Aspects of the invention are further explicated below.
I. Fine Chemicals The term 'fine chemical' is art-recognized and includes molecules produced by an organism which have applications in various industries, such as, but not limited to, the pharmaceutical, agriculture, and cosmetics industries. Such compounds include organic acids, such as tartaric acid, itaconic acid, and diaminopimelic acid, both proteinogenic and non-proteinogenic amino acids, purine and pyrimidine bases, nucleosides, and nucleotides (as described e.g. in Kuninaka, A. (1996) Nucleotides and related compounds, p. 561-612, in Biotechnology vol. 6, Rehm el al., eds. VCH: Wcinhcim, and references contained therein), lipids, both saturated and unsaturated fatty acids arachidonic acid), diols propane diol, and butane diol), carbohydrates hyaluronic acid and trehalose), aromatic compounds aromatic amines, vanillin, and indigo), vitamins and cofactors (as described in Ullmann's Encyclopedia of Industrial Chemistry, vol. A27, "Vitamins", p. 443-613 (1996) VCH: Weinheim and references therein; and Ong, Niki, E. Packer, L. (1995) "Nutrition, Lipids, Health, and Disease" Proceedings of the UNESCO/Confederation of Scientific and Technological Associations in Malaysia, and the Society for Free Radical Research Asia, held Sept. 1-3, 1994 at Penang, Malaysia, AOCS Press, (1995)), enzymes, polyketides (Cane et al. (1998) Science 282: 63-68), and all other chemicals described in WO 01/00804 PCT/IB00/00922 Gutcho (1983) Chemicals by Fermentation, Noyes Data Corporation, ISBN: 0818805086 and references therein. The metabolism and uses of certain of these fine chemicals are further explicated below.
A. Amino Acid Metabolism and Uses Amino acids comprise the basic structural units of all proteins, and as such are essential for normal cellular functioning in all organisms. The term "amino acid" is artrecognized. The proteinogenic amino acids, of which there are 20 species, serve as structural units for proteins, in which they are linked by peptide bonds, while the nonproteinogenic amino acids (hundreds of which are known) are not normally found in proteins (see Ulmann's Encyclopedia of Industrial Chemistry, vol. A2, p. 57-97 VCH: Weinheim (1985)). Amino acids may be in the D- or L- optical configuration, though Lamino acids are generally the only type found in naturally-occurring proteins.
Biosynthetic and degradative pathways of each of the 20 proteinogenic amino acids have been well characterized in both prokaryotic and eukaryotic cells (see, for example, Stryer, L. Biochemistry, 3 r d edition, pages 578-590 (1988)). The 'essential' amino acids (histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine), so named because they are generally a nutritional requirement due to the complexity of their biosyntheses, are readily converted by simple biosynthetic pathways to the remaining 11 'nonessential' amino acids (alanine, arginine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, proline, serine, and tyrosine). Higher animals do retain the ability to synthesize some of these amino acids, but the essential amino acids must be supplied from the diet in order for normal protein synthesis to occur.
Aside from their function in protein biosynthesis, these amino acids are interesting chemicals in their own right, and many have been found to have various applications in the food, feed, chemical, cosmetics, agriculture, and pharmaceutical industries. Lysine is an important amino acid in the nutrition not only of humans, but also ofmonogastric animals such as poultry and swine. Glutamate is most commonly used as a flavor additive (mono-sodium glutamate, MSG) and is widely used throughout the food industry, as are aspartate, phenylalanine, glycine, and cysteine. Glycine, Lmethionine and tryptophan are all utilized in the pharmaceutical industry. Glutamine, valine, leucine, isoleucine, histidine, arginine, proline, serine and alanine are of use in WO 01/00804 PCT/IB00/00922 11 both the pharmaceutical and cosmetics industries. Threonine, tryptophan, and D/ Lmethionine are common feed additives. (Leuchtenberger, W. (1996) Amino aids technical production and use, p. 466-502 in Rehm et al. (eds.) Biotechnology vol. 6, chapter 14a, VCH: Weinheim). Additionally, these amino acids have been found to be useful as precursors for the synthesis of synthetic amino acids and proteins, such as Nacetylcysteine, S-carboxymethyl-L-cysteine, (S)-5-hydroxytryptophan, and others described in Ulmann's Encyclopedia of Industrial Chemistry, vol. A2, p. 57-97, VCH: Weinheim, 1985.
The biosynthesis of these natural amino acids in organisms capable of producing them, such as bacteria, has been well characterized (for review of bacterial amino acid biosynthesis and regulation thereof, see Umbarger, H.E.(1978) Ann. Rev.
Biochem. 47: 533-606). Glutamate is synthesized by the reductive amination ofaketoglutarate, an intermediate in the citric acid cycle. Glutamine, proline, and arginine are each subsequently produced from glutamate. The biosynthesis of serine is a threestep process beginning with 3-phosphoglycerate (an intermediate in glycolysis), and resulting in this amino acid after oxidation, transamination, and hydrolysis steps. Both cysteine and glycine are produced from serine; the former by the condensation of homocysteine with serine, and the latter by the transferal of the side-chain -carbon atom to tetrahydrofolate, in a reaction catalyzed by serine transhydroxymethylase.
Phenylalanine, and tyrosine are synthesized from the glycolytic and pentose phosphate pathway precursors erythrose 4-phosphate and phosphoenolpyruvate in a 9-step biosynthetic pathway that differ only at the final two steps after synthesis of prephenate.
Tryptophan is also produced from these two initial molecules, but its synthesis is an 11step pathway. Tyrosine may also be synthesized from phenylalanine, in a reaction catalyzed by phenylalanine hydroxylase. Alanine, valine, and leucine are all biosynthetic products of pyruvate, the final product of glycolysis. Aspartate is formed from oxaloacetate, an intermediate of the citric acid cycle. Asparagine, methionine, threonine, and lysine are each produced by the conversion ofaspartate. Isoleucine is formed from threonine. A complex 9-step pathway results in the production ofhistidine from 5-phosphoribosyl-l-pyrophosphate, an activated sugar.
Amino acids in excess of the protein synthesis needs of the cell cannot be stored, and are instead degraded to provide intermediates for the major metabolic pathways of WO 01/00804 PCT/IB00/00922 -12the cell (for review see Stryer, L. Biochemistry 3 r d ed. Ch. 21 "Amino Acid Degradation and the Urea Cycle" p. 495-516 (1988)). Although the cell is able to convert unwanted amino acids into useful metabolic intermediates, amino acid production is costly in terms of energy, precursor molecules, and the enzymes necessary to synthesize them.
Thus it is not surprising that amino acid biosynthesis is regulated by feedback inhibition, in which the presence of a particular amino acid serves to slow or entirely stop its own production (for overview of feedback mechanisms in amino acid biosynthetic pathways, see Strycr, L. Biochemistry, 3 r d ed. Ch. 24: "Biosynthesis of Amino Acids and Heme" p.
575-600 (1988)). Thus, the output of any particular amino acid is limited by the amount of that amino acid present in the cell.
B. Vitamin, Cofactor, and Nutraceutical Metabolism and Uses Vitamins, cofactors, and nutraceuticals comprise another group of molecules which the higher animals have lost the ability to synthesize and so must ingest, although they are readily synthesized by other organisms, such as bacteria. These molecules are either bioactive substances themselves, or are precursors of biologically active substances which may serve as electron carriers or intermediates in a variety of metabolic pathways. Aside from their nutritive value, these compounds also have significant industrial value as coloring agents, antioxidants, and catalysts or other processing aids. (For an overview of the structure, activity, and industrial applications of these compounds, see, for example, Ullman's Encyclopedia of Industrial Chemistry, "Vitamins" vol. A27, p. 443-613, VCH: Weinheim, 1996.) The term "vitamin" is artrecognized, and includes nutrients which are required by an organism for normal functioning, but which that organism cannot synthesize by itself. The group of vitamins may encompass cofactors and nutraceutical compounds. The language "cofactor" includes nonproteinaceous compounds required for a normal enzymatic activity to occur. Such compounds may be organic or inorganic; the cofactor molecules of the invention are preferably organic. The term "nutraceutical" includes dietary supplements having health benefits in plants and animals, particularly humans. Examples of such molecules are vitamins, antioxidants, and also certain lipids polyunsaturated fatty acids).
WO 01/00804 PCT/IB00/00922 -13- The biosynthesis of these molecules in organisms capable of producing them, such as bacteria, has been largely characterized (Ullman's Encyclopedia of Industrial Chemistry, "Vitamins" vol. A27, p. 4 4 3 6 1 3 VCH: Weinheim, 1996; Michal, G. (1999) Biochemical Pathways: An Atlas of Biochemistry and Molecular Biology, John Wiley Sons; Ong, Niki, E. Packer, L. (1995) "Nutrition, Lipids, Health, and Disease" Proceedings of the UNESCO/Confederation of Scientific and Technological Associations in Malaysia, and the Society for Free Radical Research Asia, held Sept.
1-3, 1994 at Penang, Malaysia, AOCS Press: Champaign, IL X, 374 S).
Thiamin (vitamin B is produced by the chemical coupling of pyrimidine and thiazole moieties. Riboflavin (vitamin B 2 is synthesized from (GTP) and ribose-5'-phosphate. Riboflavin, in turn, is utilized for the synthesis of flavin mononucleotide (FMN) and flavin adenine dinuclcotide (FAD). The family of compounds collectively termed 'vitamin B 6 pyridoxine, pyridoxamine, pyridoxaand the commercially used pyridoxin hydrochloride) are all derivatives of the common structural unit, 5-hydroxy-6-methylpyridine. Pantothenate (pantothenic acid, (R)-(+)-N-(2,4-dihydroxy-3,3-dimethyl-l-oxobutyl)-P-alanine) can be produced either by chemical synthesis or by fermentation. The final steps in pantothenate biosynthesis consist of the ATP-driven condensation of p-alanine and pantoic acid. The enzymes responsible for the biosynthesis steps for the conversion to pantoic acid, to Palanine and for the condensation to panthotenic acid are known. The metabolically active form of pantothenate is Coenzyme A, for which the biosynthesis proceeds in enzymatic steps. Pantothenate, pyridoxal-5'-phosphate, cysteine and ATP are the precursors of Coenzyme A. These enzymes not only catalyze the formation of panthothante, but also the production of (R)-pantoic acid, (R)-pantolacton, panthenol (provitamin Bs), pantetheine (and its derivatives) and coenzyme A.
Biotin biosynthesis from the precursor molecule pimeloyl-CoA in microorganisms has been studied in detail and several of the genes involved have been identified. Many of the corresponding proteins have been found to also be involved in Fe-cluster synthesis and are members of the nifS class of proteins. Lipoic acid is derived from octanoic acid, and serves as a coenzyme in energy metabolism, where it becomes part of the pyruvate dehydrogenase complex and the a-ketoglutarate dehydrogenase complex. The folates are a group of substances which are all derivatives WO 01/00804 PCT/IB00/00922 -14of folic acid, which is turn is derived from L-glutamic acid, p-amino-benzoic acid and 6methylpterin. The biosynthesis of folic acid and its derivatives, starting from the metabolism intermediates guanosine-5'-triphosphate (GTP), L-glutamic acid and pamino-benzoic acid has been studied in detail in certain microorganisms.
Corrinoids (such as the cobalamines and particularly vitamin Bi 2 and porphyrines belong to a group of chemicals characterized by a tetrapyrole ring system.
The biosynthesis of vitamin Bi2 is sufficiently complex that it has not yet been completely characterized, but many of the enzymes and substrates involved are now known. Nicotinic acid (nicotinate), and nicotinamide are pyridine derivatives which are also termed 'niacin'. Niacin is the precursor of the important coenzymes NAD (nicotinamide adenine dinucleotide) and NADP (nicotinamide adenine dinucleotidc phosphate) and their reduced forms.
The large-scale production of these compounds has largely relied on cell-free chemical syntheses, though some of these chemicals have also been produced by largescale culture of microorganisms, such as riboflavin, Vitamin B 6 pantothenate, and biotin. Only Vitamin B12 is produced solely by fermentation, due to the complexity of its synthesis. In vitro methodologies require significant inputs of materials and time, often at great cost.
C Purine, Pyrimidine, Nucleoside and Nucleotide Metabolism and Uses Purine and pyrimidine metabolism genes and their corresponding proteins are important targets for the therapy of tumor diseases and viral infections. The language "purine" or "pyrimidine" includes the nitrogenous bases which are constituents of nucleic acids, co-enzymes, and nucleotides. The term "nucleotide" includes the basic structural units of nucleic acid molecules, which are comprised of a nitrogenous base, a pentose sugar (in the case of RNA, the sugar is ribose; in the case of DNA, the sugar is D-deoxyribose), and phosphoric acid. The language "nucleoside" includes molecules which serve as precursors to nucleotides, but which are lacking the phosphoric acid moiety that nucleotides possess. By inhibiting the biosynthesis of these molecules, or their mobilization to form nucleic acid molecules, it is possible to inhibit RNA and DNA synthesis; by inhibiting this activity in a fashion targeted to cancerous cells, the ability of tumor cells to divide and replicate may be inhibited. Additionally, there are WO 01/00804 PCT/IB00/00922 nucleotides which do not form nucleic acid molecules, but rather serve as energy stores AMP) or as coenzymes FAD and NAD).
Several publications have described the use of these chemicals for these medical indications, by influencing purine and/or pyrimidine metabolism Christopherson, R.I. and Lyons, S.D. (1990) "Potent inhibitors of de novo pyrimidine and purine biosynthesis as chemotherapeutic agents." Med Res. Reviews 10: 505-548). Studies of enzymes involved in purine and pyrimidine metabolism have been focused on the development of new drugs which can be used, for example, as immunosuppressants or anti-proliferants (Smith, (1995) "Enzymes in nucleotide synthesis." Curr. Opin.
Struct. Biol. 5: 752-757; (1995) Biochem Soc. Transact. 23: 877-902). However, purine and pyrimidine bases, nucleosides and nucleotides have other utilities: as intermediates in the biosynthesis of several fine chemicals thiamine, S-adenosyl-methionine, folates, or riboflavin), as energy carriers for the cell ATP or GTP), and for chemicals themselves, commonly used as flavor enhancers IMP or GMP) or for several medicinal applications (see, for example, Kuninaka, A. (1996) Nucleotides and Related Compounds in Biotechnology vol. 6, Rehm et al, eds. VCH: Weinheim, p. 561- 612). Also, enzymes involved in purine, pyrimidine, nucleoside, or nucleotide metabolism are increasingly serving as targets against which chemicals for crop protection, including fungicides, herbicides and insecticides, are developed.
The metabolism of these compounds in bacteria has been characterized (for reviews see, for example, Zalkin, H. and Dixon, J.E. (1992) "de novo purine nucleotide biosynthesis", in: Progress in Nucleic Acid Research and Molecular Biology, vol. 42, Academic Press:, p. 259-287; and Michal, G. (1999) "Nucleotides and Nucleosides", Chapter 8 in: Biochemical Pathways: An Atlas of Biochemistry and Molecular Biology, Wiley: New York). Purine metabolism has been the subject of intensive research, and is essential to the normal functioning of the cell. Impaired purine metabolism in higher animals can cause severe disease, such as gout. Purine nucleotides are synthesized from in a series of steps through the intermediate compound phosphate (IMP), resulting in the production of guanosine-5'-monophosphate (GMP) or adenosine-5'-monophosphate (AMP), from which the triphosphate forms utilized as nucleotides are readily formed. These compounds are also utilized as energy stores, so their degradation provides energy for many different biochemical processes in the cell.
WO 01/00804 PCT/IB00/00922 -16- Pyrimidine biosynthesis proceeds by the formation of uridine-5'-monophosphate (UMP) from ribose-5-phosphate. UMP, in turn, is converted to cytidine-5'-triphosphate (CTP).
The deoxy- forms of all of these nucleotides are produced in a one step reduction reaction from the diphosphate ribose form of the nucleotide to the diphosphate deoxyribose form of the nucleotide. Upon phosphorylation, these molecules are able to participate in DNA synthesis.
D. Trehalose Metabolism and Uses Trehalose consists of two glucose molecules, bound in a, a-l,l linkage. It is commonly used in the food industry as a sweetener, an additive for dried or frozen foods, and in beverages. However, it also has applications in the pharmaceutical, cosmetics and biotechnology industries (see, for example, Nishimoto et al., (1998) U.S.
Patent No. 5,759,610; Singer, M.A. and Lindquist, S. (1998) Trends Biotech. 16: 460- 467; Paiva, C.L.A. and Panek, A.D. (1996) Biotech. Ann. Rev. 2: 293-314; and Shiosaka, M. (1997) J. Japan 172: 97-102). Trehalose is produced by enzymes from many microorganisms and is naturally released into the surrounding medium, from which it can be collected using methods known in the art.
II. Resistance to Damage from Chemicals, Environmental Stress, and Antibiotics Production of fine chemicals is typically performed by large-scale culture of bacteria developed to produce and secrete large quantities of these molecules. However, this type of large-scale fermentation results in the subjection of the microorganisms to stresses of various kinds. These stresses include environmental stress and chemical stress.
A. Resistance to Environmental Stress Examples of environmental stresses typically encountered in large-scale fermentative culture include mechanical stress, heat stress, stress due to limited oxygen, stress due to oxygen radicals, pH stress, and osmotic stress. The stirring mechanism used in most large-scale fermentors to ensure aeration of the culture produces heat, thus increasing the temperature of the culture. Increases in temperature induce the wellcharacterized heat shock response, in which a set of proteins are expressed which not WO 01/00804 PCT/IB00/00922 -17only aid in the survival of the bacterium in the face of high temperatures, but also increase survival in response to a number of other environmental stresses (see Neidhardt, et al., eds. (1996) E. coli and Salmonella. ASM Press: Washington, p. 1382-1399; Wosten, M. M. (1998) FEMS Microbiology Reviews 22(3): 127-50; Bahl, H. et al. (1995) FEMS Microbiology Reviews 17(3): 341-348; Zimmerman, J.L., Cohill, P.R. (1991) New Biologist 641-650; Samali, and Orrenius, S. (1998) Cell. Stress Chaperones 228-236, and references contained therein from each of these citations). Regulation of the heat shock response in bacteria is facilitated by specific sigma factors and other cellular regulators of gene expression (Hecker, M., Volker, U (1998). Molecular Microbiology 29(5): 1129-1136). One of the largest problems that the cell encounters when exposed to high temperature is that protein folding is impaired; nascent proteins have sufficient kinetic energy in high temperature circumstances that it is difficult for the growing polypeptide chain to remain in a stable conformation long enough to fold properly. Thus, two of the key types of proteins expressed during the heat shock response consist of chaperones (proteins which assist in the folding or unfolding of other proteins see, Fink, A.L. (1999) Physiol. Rev.
79(2): 425-449), and proteases, which can destroy any improperly folded proteins.
Examples of chaperones expressed during the heat shock response include GroEL and DNAK; proteases known to be expressed during this cellular reaction to heat shock include Lon, FtsH, and CIpB.
Other environmental stresses besides heat may also provoke a stress response.
Though the fermentor stirring process is meant to introduce oxygen into the culture, oxygen may remain in limited supply, particularly when the culture is advanced in growth and the oxygen needs of the culture are thereby increased; an insufficient supply of oxygen is another stress for the microorganism. Cells in fermentor cultures are also subjected to a number of osmotic stresses, particularly when nutrients are added to the culture, resulting in a high extracellular and low intracellular concentration of these molecules. Further, the large quantities of the desired molecules produced by these organisms in culture may contribute to osmotic stress of the bacteria. Lastly, aerobic metabolism such as that used by C. glutamicum results in carbon dioxide as a waste product; secretion of this molecule may acidify the culture medium due to conversion of this molecule to carboxylic acid. Thus, bacteria in culture are also frequently subjected WO 01/00804 PCT/IB00/00922 -18to acidic pH stress. The converse may also be true when high levels of basic waste molecules such as ammonium are present in the culture medium, the bacteria in culture may be subjected to basic pH stress as well.
To combat such environmental stresses, bacteria have elegant gene systems which are expressed upon exposure to one or more stresses, such as the aforementioned heat shock system. Genes expressed in response to osmotic stress, for example, encode proteins capable of transporting or synthesizing compatible solutes such that osmotic intake or export of a particular molecule is slowed to manageable levels. Other examples of stress-induced bacterial proteins are those involved in trehalose biosynthesis, those encoding enzymes involved in ppGpp metabolism, those involved in signal transduction, particularly those encoding two-component systems which are sensitive to osmotic pressure, and those encoding transcription factors which are responsive to a variety of stress factors RssB analogues and/or sigma factors). Many other such genes and their protein products are known in the art.
B. Resistance to Chemical Stress Aside from environmental stresses, cells may also experience a number of chemical stresses. These may fall into two categories. The first are natural waste products of metabolism and other cellular processes which are secreted by the cell to the surrounding medium. The second are chemicals present in the extracellular medium which do not originate from the cell. Generally, when cells excrete toxic waste products from the concentrated intracellular cytoplasm into the relatively much more dilute extracellular medium, these products dissipate such that extracellular levels of the possibly toxic compound are quite low. However, in large-scale fermentative culture of the bacterium, this may not be the case: so many bacteria are grown in a relatively small environment and at such a high metabolic rate that waste products may accumulate in the medium to nearly toxic levels. Examples of such wastes are carbon dioxide, metal ions, and reactive oxygen species such as hydrogen peroxide. These compounds may interfere with the activity or structure of cell surface molecules, or may re-enter the cell, where they can seriously damage proteins and nucleic acids alike. Certain other chemicals hazardous to the normal functioning of cells may be naturally found in the extracellular medium. For example, metal ions such as mercury, cadmium, nickel or WO 01/00804 PCT/IB00/00922 19copper are frequently found in water sources, and may form tight complexes with cellular enzymes which prevent the normal functioning of these proteins.
C. Resistance to Antibiotics Bacteriocidal proteins or antibiotics, may also be found in the extracellular milieu, either through the intervention of the researcher, or as a natural product from another organism, utilized to gain a competitive advantage. Microorganisms have several art-known mechanisms to protect themselves against antimicrobial chemicals.
Degradation, modification, and export of compounds toxic to the cell are common methods by which microorganisms eliminate or detoxify antibiotics. Cytoplasmic 'efflux-pumps' are known in several prokaryotes and show similarities to the so-called 'multidrug resistance' proteins from higher eukaryotes (Neyfakh, A. el al. (1991) Proc. Natl. Acad. Sci. USA 88: 4781-4785). Examples of such proteins include emrAB from E. coli (Lomovskaya, 0. and K. Lewis (1992) Proc. Natl. Acad. Sci. USA 89: 8938-8942), ImrB from B. subtilis (Kumano, M. et al. (1997) Microbiology 143: 2775- 2782), smr from S. aureus (Grinius, L.G. et al. (1992) Plasmid 27: 119-129) or cmr from C. glutamicum (Kaidoh, K. et al. (1997) Micro. Drug Resist. 3: 345-350). .C.
glutamicum itself is non-pathogenic, in contrast to several other members of the genus Corynebacterium, such as C. diphtheriae or C. pseudotuberculosis. Several pathogenic Corynebacteria are known to have multiple resistances against a variety of antibiotics, such as C. jeikeium and C. urealyticum (Soriano, F. et al. (1995) Antimicrob. Agents Chemother. 39: 208-214).
Lincosamides are recognized as effective antibiotics against Corynebacterium species (Soriano, F. et al. (1995) Antimicrob. Agents Chemother. 39: 208-214). An unexpected result of the present invention was the identification of a gene encoding a lincosamide-resistance protein (in particular, a lincomycin-resistance protein). The LMRB protein from C. glutamicum shows 40% homology to the product of the ImrB gene from B. subtilis (see Genbank accession no. AL009126), as calculated using version 1.7 of the program CLUSTALW (Thompson, Higgins, Gibson, T. J.
(1994) Nucl. Acids Res. 22: 4673-4680) using standard parameters (PAIRWISE ALIGNMENT PARAMETERS: slow/accurate alignments: Gap Open Penalty 10.00, Gap Extension Penalty 0.10, Protein weight matrix BLOSUM 30, DNA weight WO 01/00804 PCT/IB00/00922 matrix IUB, Fast/Approximate alignments: Gap penalty 3, K-tuple (word) size 1, No. of top diagonals 5, Window size 5, Toggle Slow/Fast pairwise alignments slow. Multiple alignment parameters: Gap Opening Penalty 10.00, Gap Extension Penalty 0.05, Delay divergent sequences 40%, DNA transitions weight 0.50, Protein weight matrix BLOSUM series, DNA weight matrix IUB, Use negative matrix OFF).
Environmental stress, chemical stress, and antibiotic or other antimicrobial stress may influence the behavior of the microorganisms during fermentor culture, and may have an impact on the production of the desired compound from these organisms.
For example, osmotic stress of a microorganism may cause inappropriate or inappropriately rapid uptake of one or more compounds which can ultimately lead to cellular damage or death due to osmotic shock. Similarly, chemicals present in the culture, either exogenously added antimicrobial compounds intended to eliminate unwanted microbes) or generated by the bacteria themselves waste compounds such as heavy metals or oxygen radicals, or even antimicrobial compounds) may result in inhibition of fine chemical production or even death of the organism. The genes of the invention encode C. glutamicum proteins which act to prevent cell damage or death, by specifically counteracting the source or effect of the environmental or chemical stress.
II. Elements and Methods of the Invention The present invention is based, at least in part, on the discovery of novel molecules, referred to herein as SRT nucleic acid and protein molecules, which increase the ability of C glutamicum to survive in chemically or environmentally hazardous settings. In one embodiment, the SRT molecules function to confer resistance to one or more environmental or chemical stresses to C. glutamicum. In a preferred embodiment, the activity of the SRT molecules of the present invention has an impact on the production of a desired fine chemical by this organism. In a particularly preferred embodiment, the SRT molecules of the invention are modulated in activity, such that the yield, production, and/or efficiency of production of one or more fine chemicals from C.
glutamicum is also modulated.
WO 01/00804 PCT/IBOO/00922 -21- The language, "SRT protein" or "SRT polypeptide" includes proteins which participate in the resistance of C. gluramicum to one or more environmental or chemical stresses. Examples of SRT proteins include those encoded by the SRT genes set forth in Table I and by the odd-numbered SEQ ID NOs. The terms "SRT gene" or "SRT nucleic acid sequence" include nucleic acid sequences encoding an SRT protein, which consist of a coding region and also corresponding untranslated 5' and 3' sequence regions. Examples of SRT genes include those set forth in Table 1. The terms "production" or "productivity" are art-recognized and include the concentration of the fermentation product (for example, the desired fine chemical) formed within a given time and a given fermentation volume kg product per hour per liter). The term "efficiency of production" includes the time required for a particular level of production to be achieved (for example, how long it takes for the cell to attain a particular rate of output of a fine chemical). The term "yield" or "product/carbon yield" is art-recognized and includes the efficiency of the conversion of the carbon source into the product fine chemical). This is generally written as, for example, kg product per kg carbon source. By increasing the yield or production of the compound, the quantity of recovered molecules, or of useful recovered molecules of that compound in a given amount of culture over a given amount of time is increased. The terms "biosynthesis" or a "biosynthetic pathway" are art-recognized and include the synthesis of a compound, preferably an organic compound, by a cell from intermediate compounds in what may be a multistep and highly regulated process. The terms "degradation" or a "degradation pathway" are art-recognized and include the breakdown of a compound, preferably an organic compound, by a cell to degradation products (generally speaking, smaller or less complex molecules) in what may be a multistep and highly regulated process. The language "metabolism" is art-recognized and includes the totality of the biochemical reactions that take place in an organism. The metabolism of a particular compound, then, the metabolism of an amino acid such as glycine) comprises the overall biosynthetic, modification, and degradation pathways in the cell related to this compound. The terms "resistance" and "tolerance" are art-known and include the ability of a cell to not be affected by exposure to a chemical or an environment which would otherwise be detrimental to the normal functioning of these organisms. The terms "stress" or "hazard" include factors which are detrimental to the normal functioning of WO 01/00804 PCT/IB00/00922 -22cells such as C. glulamicum. Examples of stresses include "chemical stress", in which a cell is exposed to one or more chemicals which are detrimental to the cell, and "environmental stress" where a cell is exposed to an environmental condition outside of those to which it is adapted. Chemical stresses may be either natural metabolic waste products such as, but not limited to reactive oxygen species or carbon dioxide, or chemicals otherwise present in the environment, including, but not limited to heavy metal ions or bacteriocidal proteins such as antibiotics. Environmental stresses may be, but are not limited to temperatures outside of the normal range, suboptimal oxygen availability, osmotic pressures, or extremes of pH, for example.
In another embodiment, the SRT molecules of the invention are capable of modulating the production of a desired molecule, such as a fine chemical, in a microorganism such as C glulamicum. Using recombinant genetic techniques, one or more of the SRT proteins of the invention may be manipulated such that its function is modulated. The alteration of activity of stress response, resistance or tolerance genes such that the cell is increased in tolerance to one or more stresses may improve the ability of that cell to grow and multiply in the relatively stressful conditions of largescale fermentor culture. For example, by overexpressing or engineering a heat-shock induced chaperone molecule such that it is optimized in activity, one may increase the ability of the bacterium to correctly fold proteins in the face of nonoptimal temperature conditions. By having fewer misfolded (and possibly misregulated or nonfunctional) proteins, the cell is increased in its ability to function normally in such a culture, which should in turn provide increased viability. This overall increase in number of cells having greater viability and activity in the culture should also result in an increase in the yield, production, and/or efficiency of production of one or more desired fine chemicals, due at least to the relatively greater number of cells producing these chemicals in the culture.
The isolated nucleic acid sequences of the invention are contained within the genome of a Corynebacterium glulamicum strain available through the American Type Culture Collection, given designation ATCC 13032. The nucleotide sequence of the isolated C. glutamicum SRT DNAs and the predicted amino acid sequences of the C.
glutamicum SRT proteins are shown the Sequence Listing as odd-numbered SEQ ID NOs and even-numbered SEQ ID NOs, respectively.,.
WO 01/00804 PCT/IBOO/00922 -23- Computational analyses were performed which classified and/or identified these nucleotide sequences as sequences which encode chemical and environmental stress, resistance, and tolerance proteins.
The present invention also pertains to proteins which have an amino acid sequence which is substantially homologous to an amino acid sequence of the invention the sequence of an even-numbered SEQ ID NO of the Sequence Listing). As used herein, a protein which has an amino acid sequence which is substantially homologous to a selected amino acid sequence is least about 50% homologous to the selected amino acid sequence, the entire selected amino acid sequence. A protein which has an amino acid sequence which is substantially homologous to a selected amino acid sequence can also be least about 50-60%, preferably at least about 60-70%, and more preferably at least about 70-80%, 80-90%, or 90-95%, and most preferably at least about 96%, 97%, 98%, 99% or more homologous to the selected amino acid sequence.
Ranges and identity values intermediate to the above-recited values, 75%-80% identical, 85-87% identical, 91-92% identical) are also intended to be encompassed by the present invention. For example, ranges of identity values using a combination of any of the above values recited as upper and/or lower limits are intended to be included.
The SRT proteins or biologically active portions or fragments thereof of the invention can confer resistance or tolerance to one or more chemical or environmental stresses, or may have one or more of the activities set forth in Table 1.
Various aspects of the invention are described in further detail in the following subsections: A. Isolated Nucleic Acid Molecules One aspect of the invention pertains to isolated nucleic acid molecules that encode SRT polypeptides or biologically active portions thereof, as well as nucleic acid fragments sufficient for use as hybridization probes or primers for the identification or amplification of SRT-encoding nucleic acid SRT DNA). As used herein, the term "nucleic acid molecule" is intended to include DNA molecules cDNA or genomic DNA) and RNA molecules mRNA) and analogs of the DNA or RNA generated using nucleotide analogs. This term also encompasses untranslated sequence located at both the 3' and 5' ends of the coding region of the gene: at least about 100 nucleotides WO 01/00804 PCT/IB00/00922 -24of sequence upstream from the 5' end of the coding region and at least about nucleotides of sequence downstream from the 3'end of the coding region of the gene.
The nucleic acid molecule can be single-stranded or double-stranded, but preferably is double-stranded DNA. An "isolated" nucleic acid molecule is one which is separated from other nucleic acid molecules which are present in the natural source of the nucleic acid. Preferably, an "isolated" nucleic acid is free of sequences which naturally flank the nucleic acid sequences located at the 5' and 3' ends of the nucleic acid) in the genomic DNA of the organism from which the nucleic acid is derived. For example, in various embodiments, the isolated SRT nucleic acid molecule can contain less than about 5 kb, 4kb, 3kb, 2kb, 1 kb, 0.5 kb or 0.1 kb of nucleotide sequences which naturally flank the nucleic acid molecule in genomic DNA of the cell from which the nucleic acid is derived a C. glutamicum cell). Moreover, an "isolated" nucleic acid molecule, such as a DNA molecule, can be substantially free of other cellular material, or culture medium when produced by recombinant techniques, or chemical precursors or other chemicals when chemically synthesized.
A nucleic acid molecule of the present invention, a nucleic acid molecule having a nuclcotide sequence of an odd-numbered SEQ ID NO of the Sequence Listing, or a portion thereof, can be isolated using standard molecular biology techniques and the sequence information provided herein. For example, a C. glutamicum SRT DNA can be isolated from a C. glutamicum library using all or portion of one of the odd-numbered SEQ ID NO sequences of the Sequence Listing as a hybridization probe and standard hybridization techniques as described in Sambrook, Fritsh, E. and Maniatis, T. Molecular Cloning: A Laboratory Manual. 2nd, ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1989).
Moreover, a nucleic acid molecule encompassing all or a portion of one of the nucleic acid sequences of the invention an odd-numbered SEQ ID NO:) can be isolated by the polymerase chain reaction using oligonucleotide primers designed based upon this sequence a nucleic acid molecule encompassing all or a portion of one of the nucleic acid sequences of the invention an odd-numbered SEQ ID NO of the Sequence Listing) can be isolated by the polymerase chain reaction using oligonucleotide primers designed based upon this same sequence). For example, mRNA can be isolated from normal endothelial cells by the guanidinium-thiocyanate WO 01/00804 PCT/IB00/00922 extraction procedure of Chirgwin et al. (1979) Biochemistry 18: 5294-5299) and DNA can be prepared using reverse transcriptase Moloney MLV reverse transcriptase, available from Gibco/BRL, Bethesda, MD; or AMV reverse transcriptase, available from Seikagaku America, Inc., St. Petersburg, FL). Synthetic oligonucleotide primers for polymerase chain reaction amplification can be designed based upon one of the nucleotide sequences shown in the Sequence Listing. A nucleic acid of the invention can be amplified using cDNA or, alternatively, genomic DNA, as a template and appropriate oligonucleotide primers according to standard PCR amplification techniques. The nucleic acid so amplified can be cloned into an appropriate vector and characterized by DNA sequence analysis. Furthermore, oligonucleotides corresponding to an SRT nucleotide sequence can be prepared by standard synthetic teclniques, e.g., using an automated DNA synthesizer.
In a preferred embodiment, an isolated nucleic acid molecule of the invention comprises one of the nucleotide sequences shown in the Sequence Listing. The nucleic acid sequences of the invention, as set forth in the Sequence Listing, correspond to the Corynebacterium glutamicum SRT DNAs of the invention. This DNA comprises sequences encoding SRT proteins the "coding region", indicated in each oddnumbered SEQ ID NO: sequence in the Sequence Listing), as well as 5' untranslated sequences and 3' untranslated sequences, also indicated in each odd-numbered SEQ ID NO: in the Sequence Listing. Alternatively, the nucleic acid molecule can comprise only the coding region of any of the nucleic acid sequences of the Sequence Listing.
For the purposes of this application, it will be understood that each of the nucleic acid and amino acid sequences set forth in the Sequence Listing has an identifying RXA, RXN, or RXS number having the designation "RXA", "RXN", or "RXS" followed by digits RXA01524, RXN00493, or RXSO1027). Each of the nucleic acid sequences comprises up to three parts: a 5' upstream region, a coding region, and a downstream region. Each of these three regions is identified by the same RXA, RXN, or RXS designation to eliminate confusion. The recitation "one of the odd-numbered sequences of the Sequence Listing", then, refers to any of the nucleic acid sequences in the Sequence Listing,, which may be also be distinguished by their differing RXA, RXN, or RXS designations. The coding region of each of these sequences is translated into a corresponding amino acid sequence, which is also et forth in the Sequence Listing, as an WO 01/00804 PCT/IB00/00922 -26even-numbered SEQ ID NO: immediately following the corresponding nucleic acid sequence. For example, the coding region for RXA01524 is set forth in SEQ ID NO:1, while the amino acid sequence which it encodes is set forth as SEQ ID NO:2. The sequences of the nucleic acid molecules of the invention are identified by the same RXA, RXN, or RXS designations as the amino acid molecules which they encode, such that they can be readily correlated. For example, the amino acid sequence designated RXA01524 is a translation of the coding region of the nucleotide sequence of nucleic acid molecule RXA01524, the amino acid sequence designated RXN00034 is a translation of the coding region of the nucleotide sequence of nucleic acid molecule RXN00034, and the amino acid sequence in designated RXS00568 is a translation of the coding region of the nucleotide sequence of nucleic acid molecule RXS00568. The correspondence between the RXA, RXN, and RXS nucleotide and amino acid sequences of the invention and their assigned SEQ ID NOs is set forth in Table 1.
Several of the genes of the invention are "F-designated genes". An F-designated gene includes those genes set forth in Table 1 which have an in front of the RXA, RXN, or RXS designation. For example, SEQ ID NO:7, designated, as indicated on Table 1, as "F RXA00498", is an F-designated gene, as are SEQ ID NOs: 25, 33, and 37 (designated on Table 1 as "F RXA01345", "F RXA02543", and "F RXA02282", respectively).
In one embodiment, the nucleic acid molecules of the present invention are not intended to include those compiled in Table 2. In the case of the dapD gene, a sequence for this gene was published in Wehrmann, et al. (1998)J. Bacteriol. 180(12): 3159- 3165. However, the sequence obtained by the inventors of the present application is significantly longer than the published version. It is believed that the published version relied on an incorrect start codon, and thus represents only a fragment of the actual coding region.
In another preferred embodiment, an isolated nucleic acid molecule of the invention comprises a nucleic acid molecule which is a complement of one of the nucleotide sequences of the invention a sequence of an odd-numbered SEQ ID NO: of the Sequence Listing, or a portion thereof. A nucleic acid molecule which is complementary to one of the nucleotide sequences of the invention is one which is sufficiently complementary to one of the nucleotide sequences shown in the Sequence WO 01/00804 PCT/IB00/00922 -27- Listing the sequence of an odd-numbered SEQ ID NO:) such that it can hybridize to one of the nucleotide sequences of the invention, thereby forming a stable duplex.
In still another preferred embodiment, an isolated nucleic acid molecule of the invention comprises a nucleotide sequence which is at least about 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, or 60%, preferably at least about 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, or more preferably at least about 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, or 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, or 90%, or 91%, 92%, 93%, 94%, and even more preferably at least about 95%, 96%, 97%, 98%, 99% or more homologous to a nucleotide sequence of the invention a sequence of an odd-numbered SEQ ID NO: of the Sequence Listing), or a portion thereof. Ranges and identity values intermediate to the above-recited ranges, 70-90% identical or 80-95% identical) are also intended to be encompassed by the present invention. For example, ranges of identity values using a combination of any of the above values recited as upper and/or lower limits are intended to be included. In an additional preferred embodiment, an isolated nucleic acid molecule of the invention comprises a nucleotide sequence which hybridizes, hybridizes under stringent conditions, to one of the nucleotide sequences of the invention,, or a portion thereof.
Moreover, the nucleic acid molecule of the invention can comprise only a portion of the coding region of the sequence of one of the odd-numbered SEQ ID NOs of the Sequence Listing for example a fragment which can be used as a probe or primer or a fragment encoding a biologically active portion of an SRT protein. The nucleotide sequences determined from the cloning of the SRT genes from C. glutamicum allows for the generation of probes and primers designed for use in identifying and/or cloning SRT homologues in other cell types and organisms, as well as SRT homologues from other Corynebacteria or related species. The probe/primer typically comprises substantially purified oligonucleotide. The oligonucleotide typically comprises a region of nucleotide sequence that hybridizes under stringent conditions to at least about 12, preferably about more preferably about 40, 50 or 75 consecutive nucleotides of a sense strand of one of the nucleotide sequences of the invention a sequence of one of the oddnumbered SEQ ID NOs of the Sequence Listing),, an anti-sense sequence of one of these sequences, or naturally occurring mutants thereof. Primers based on a nucleotide sequence of the invention can be used in PCR reactions to clone SRT homologues.
WO 01/00804 PCT/IB00/00922 -28- Probes based on the SRT nucleotide sequences can be used to detect transcripts or genomic sequences encoding the same or homologous proteins. In preferred embodiments, the probe further comprises a label group attached thereto, e.g. the label group can be a radioisotope, a fluorescent compound, an enzyme, or an enzyme cofactor. Such probes can be used as a part of a diagnostic test kit for identifying cells which misexpress an SRT protein, such as by measuring a level of an SRT-encoding nucleic acid in a sample of cells, detecting SRT mRNA levels or determining whether a genomic SRT gene has been mutated or deleted.
In one embodiment, the nucleic acid molecule of the invention encodes a protein or portion thereof which includes an amino acid sequence which is sufficiently homologous to an amino acid sequence of the invention a sequence of an evennumbered SEQ ID NO of the Sequence Listing) such that the protein or portion thereof maintains the ability to confer resistance or tolerance of C. glutamicum to one or more chemical or environmental stresses. As used herein, the language "sufficiently homologous" refers to proteins or portions thereof which have amino acid sequences which include a minimum number of identical or equivalent an amino acid residue which has a similar side chain as an amino acid residue in a sequence of one of the evennumbered SEQ ID NOs of the Sequence Listing) amino acid residues to an amino acid sequence of the invention such that the protein or portion thereof is capable of participating in the resistance ofC. glutamicum to one or more chemical or environmental stresses. Protein members of such metabolic pathways, as described herein, function to increase the resistance or tolerance of C. glutamicum to one or more environmental or chemical hazards or stresses. Examples of such activities are also described herein. Thus, "the function of an SRT protein" contributes to the overall resistance of C. glulamicum to elements of its surroundings which may impede its normal growth or functioning, and/or contributes, either directly or indirectly, to the yield, production, and/or efficiency of production of one or more fine chemicals.
Examples of SRT protein activities are set forth in Table 1.
In another embodiment, the protein is at least about 50-60%, preferably at least about 60-70%, and more preferably at least about 70-80%, 80-90%, 90-95%, and most preferably at least about 96%, 97%, 98%, 99% or more homologous to an entire amino acid sequence of the invention a sequence of an even-numbered SEQ ID NO: of WO 01/00804 PCT/IB00/00922 -29the Sequence Listing). Ranges and identity values intermediate to the above-recited values, 75%-80% identical, 85-87% identical, or 91-92% identical) are also intended to be encompassed by the present invention. For example, ranges of identity values using a combination of any of the above values recited as upper and/or lower limits are intended to be included.
Portions of proteins encoded by the SRT nucleic acid molecules of the invention are preferably biologically active portions of one of the SRT proteins. As used herein, the term "biologically active portion of an SRT protein" is intended to include a portion, a domain/motif, of an SRT protein that is capable of imparting resistance or tolerance to one or more environmental or chemical stresses or hazards, or has an activity as set forth in Table I. To determine whether an SRT protein or a biologically active portion thereof can increase the resistance or tolerance of C. glutamicum to one or more chemical or environmental stresses or hazards, an assay of enzymatic activity may be performed. Such assay methods are well known to those of ordinary skill in the art, as detailed in Example 8 of the Exemplification.
Additional nucleic acid fragments encoding biologically active portions of an SRT protein can be prepared by isolating a portion of one of the amino acid sequences of the invention a sequence of an even-numbered SEQ ID NO: of the Sequence Listing), expressing the encoded portion of the SRT protein or peptide by recombinant expression in vitro) and assessing the activity of the encoded portion of the SRT protein or peptide.
The invention further encompasses nucleic acid molecules that differ from one of the nucleotide sequences of the invention a sequence of an odd-numbered SEQ ID NO: of the Sequence Listing) (and portions thereof) due to degeneracy of the genetic code and thus encode the same SRT protein as that encoded by the nucleotide sequences of the invention. In another embodiment, an isolated nucleic acid molecule of the invention has a nucleotide sequence encoding a protein having an amino acid sequence shown in the Sequence Listing an even-numbered SEQ ID In a still further embodiment, the nucleic acid molecule of the invention encodes a full length C.
glutamicum protein which is substantially homologous to an amino acid sequence of the invention (encoded by an open reading frame shown in an odd-numbered SEQ ID NO: of the Sequence Listing).
WO 01/00804 PCT/IB00/00922 It will be understood by one of ordinary skill in the art that in one embodiment the sequences of the invention are not meant to include the sequences of the prior art, such as those Genbank sequences set forth in Tables 2 or 4 which were available prior to the present invention. In one embodiment, the invention includes nucleotide and amino acid sequences having a percent identity to a nucleotide or amino acid sequence of the invention which is greater than that of a sequence of the prior art a Genbank sequence (or the protein encoded by such a sequence) set forth in Tables 2 or For example, the invention includes a nucleotide sequence which is greater than and/or at least 39% identical to the nucleotide sequence designated RXA00084 (SEQ ID NO: 189), a nucleotide sequence which is greater than and/or at least 56% identical to the nucleotide sequence designated RXA00605 (SEQ ID NO: 11), and a nucleotide sequence which is greater than and/or at least 50% identical to the nucleotide sequence designated RXA00886 (SEQ ID NO:39). One of ordinary skill in the art would be able to calculate the lower threshold of percent identity for any given sequence of the invention by examining the GAP-calculated percent identity scores set forth in Table 4 for each of the three top hits for the given sequence, and by subtracting the highest GAP-calculated percent identity from 100 percent. One of ordinary skill in the art will also appreciate that nucleic acid and amino acid sequences having percent identities greater than the lower threshold so calculated at least 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, or 60%, preferably at least about 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, or 70%, more preferably at least about 71%, 72%, 73%, 74%, 76%, 77%, 78%, 79%, or 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, or or 91%, 92%, 93%, 94%, and even more preferably at least about 95%, 96%, 97%, 98%, 99% or more identical) are also encompassed by the invention.
In addition to the C glutamicum SRT nucleotide sequences set forth in the Sequence Listing as odd-numbered SEQ ID NOs, it will be appreciated by one of ordinary skill in the art that DNA sequence polymorphisms that lead to changes in the amino acid sequences of SRT proteins may exist within a population the C glutamicum population). Such genetic polymorphism in the SRT gene may exist among individuals within a population due to natural variation. As used herein, the terms "gene" and "recombinant gene" refer to nucleic acid molecules comprising an open reading frame encoding an SRT protein, preferably a C. glutamicum SRT protein. Such WO 01/00804 PCT/IB00/00922 -31 natural variations can typically result in 1-5% variance in the nucleotide sequence of the SRT gene. Any and all such nucleotide variations and resulting amino acid polymorphisms in SRT that are the result of natural variation and that do not alter the functional activity of SRT proteins are intended to be within the scope of the invention.
Nucleic acid molecules corresponding to natural variants and non-C. glutamicum homologues of the C. glutamicum SRT DNA of the invention can be isolated based on their homology to the C. glutamicum SRT nucleic acid disclosed herein using the C.
glutamicum DNA, or a portion thereof, as a hybridization probe according to standard hybridization techniques under stringent hybridization conditions. Accordingly, in another embodiment, an isolated nucleic acid molecule of the invention is at least nucleotides in length and hybridizes under stringent conditions to the nucleic acid molecule comprising a nucleotide sequence of an odd-numbered SEQ ID NO: of the Sequence Listing. In other embodiments, the nucleic acid is at least 30, 50, 100, 250 or more nucleotides in length. As used herein, the term "hybridizes under stringent conditions" is intended to describe conditions for hybridization and washing under which nucleotide sequences at least 60% homologous to each other typically remain hybridized to each other. Preferably, the conditions are such that sequences at least about 65%, more preferably at least about 70%, and even more preferably at least about or more homologous to each other typically remain hybridized to each other. Such stringent conditions are known to those of ordinary skill in the art in the art and can be found in Ausubel et al., Current Protocols in Molecular Biology, John Wiley Sons, N.Y. (1989), 6.3.1-6.3.6. A preferred, non-limiting example of stringent hybridization conditions are hybridization in 6X sodium chloride/sodium citrate (SSC) at about 45 0
C,
followed by one or more washes in 0.2 X SSC, 0.1% SDS at 50-65 0 C. Preferably, an isolated nucleic acid molecule of the invention that hybridizes under stringent conditions to a nucleotide sequence of the invention corresponds to a naturally-occurring nucleic acid molecule. As used herein, a "naturally-occurring" nucleic acid molecule refers to an RNA or DNA molecule having a nucleotide sequence that occurs in nature encodes a natural protein). In one embodiment, the nucleic acid encodes a natural C.
glutamicum SRT protein.
In addition to naturally-occurring variants of the SRT sequence that may exist in the population, one of ordinary skill in the art will further appreciate that changes can be WO 01/00804 PCT/IB00/00922 -32introduced by mutation into a nucleotide sequence of the invention, thereby leading to changes in the amino acid sequence of the encoded SRT protein, without altering the functional ability of the SRT protein. For example, nucleotide substitutions leading to amino acid substitutions at "non-essential" amino acid residues can be made in a nucleotide sequence of the invention. A "non-essential" amino acid residue is a residue that can be altered from the wild-type sequence of one of the SRT proteins an even-numbered SEQ ID NO: of the Sequence Listing) without altering the activity of said SRT protein, whereas an "essential" amino acid residue is required for SRT protein activity. Other amino acid residues, however, those that are not conserved or only semi-conserved in the domain having SRT activity) may not be essential for activity and thus are likely to be amenable to alteration without altering SRT activity.
Accordingly, another aspect of the invention pertains to nucleic acid molecules encoding SRT proteins that contain changes in amino acid residues that are not essential for SRT activity. Such SRT proteins differ in amino acid sequence from a sequence of an even-numbered SEQ ID NO: of the Sequence Listing yet retain at least one of the SRT activities described herein. In one embodiment, the isolated nucleic acid molecule comprises a nucleotide sequence encoding a protein, wherein the protein comprises an amino acid sequence at least about 50% homologous to an amino acid sequence of the invention and is capable of increasing the resistance or tolerance of C. glutamicum to one or more environmental or chemical stresses, or has one or more of the activities set forth in Table 1. Preferably, the protein encoded by the nucleic acid molecule is at least about 50-60% homologous to the amino acid sequence of one of the odd-numbered SEQ ID NOs of the Sequence Listing, more preferably at least about 60-70% homologous to one of these sequences, even more preferably at least about 70-80%, 80-90%, 90-95% homologous to one of these sequences in, and most preferably at least about 96%, 97%, 98%, or 99% homologous to one of the amino acid sequences of the invention.
To determine the percent homology of two amino acid sequences one of the amino acid sequences of the invention and a mutant form thereof) or of two nucleic acids, the sequences are aligned for optimal comparison purposes gaps can be introduced in the sequence of one protein or nucleic acid for optimal alignment with the other protein or nucleic acid). The amino acid residues or nucleotides at corresponding amino acid positions or nucleotide positions are then compared. When a position in one WO 01/00804 PCT/IB00/00922 -33sequence one of the amino acid sequences of the invention) is occupied by the same amino acid residue or nucleotide as the corresponding position in the other sequence a mutant form of the amino acid sequence), then the molecules are homologous at that position as used herein amino acid or nucleic acid "homology" is equivalent to amino acid or nucleic acid "identity"). The percent homology between the two sequences is a function of the number of identical positions shared by the sequences homology of identical positions/total of positions x 100).
An isolated nucleic acid molecule encoding an SRT protein homologous to a protein sequence of the invention a sequence of an even-numbered SEQ ID NO: of the Sequence Listing)can be created by introducing one or more nucleotide substitutions, additions or deletions into a nucleotide sequence of the invention such that one or more amino acid substitutions, additions or deletions are introduced into the encoded protein. Mutations can be introduced into one of the nucleotide sequences of the invention by standard techniques, such as site-directed mutagenesis and PCRmediated mutagenesis. Preferably, conservative amino acid substitutions are made at one or more predicted non-essential amino acid residues. A "conservative amino acid substitution" is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art. These families include amino acids with basic side chains lysine, arginine, histidine), acidic side chains aspartic acid, glutamic acid), uncharged polar side chains glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains threonine, valine, isoleucine) and aromatic side chains tyrosine, phenylalanine, tryptophan, histidine). Thus, a predicted nonessential amino acid residue in an SRT protein is preferably replaced with another amino acid residue from the same side chain family. Alternatively, in another embodiment, mutations can be introduced randomly along all or part of an SRT coding sequence, such as by saturation mutagenesis, and the resultant mutants can be screened for an SRT activity described herein to identify mutants that retain SRT activity. Following mutagenesis of one the nucleotide sequence of one of the odd-numbered SEQ ID NOs of the Sequence Listing, the encoded protein can be expressed recombinantly and the activity of the protein can WO 01/00804 PCT/IB00/00922 -34be determined using, for example, assays described herein (see Example 8 of the Exemplification).
In addition to the nucleic acid molecules encoding SRT proteins described above, another aspect of the invention pertains to isolated nucleic acid molecules which are antisense thereto. An "antisense" nucleic acid comprises a nucleotide sequence which is complementary to a "sense" nucleic acid encoding a protein, e.g., complementary to the coding strand of a double-stranded DNA molecule or complementary to an mRNA sequence. Accordingly, an antisense nucleic acid can hydrogen bond to a sense nucleic acid. The antisense nucleic acid can be complementary to an entire SRT coding strand, or to only a portion thereof. In one embodiment, an antisense nucleic acid molecule is antisense to a "coding region" of the coding strand of a nucleotide sequence encoding an SRT protein. The term "coding region" refers to the region of the nucleotide sequence comprising codons which are translated into amino acid residues the entire coding region of SEQ ID NO.: 120 (RXA00600) comprises nucleotides 1 to1098). In another embodiment, the antisense nucleic acid molecule is antisense to a "noncoding region" of the coding strand of a nucleotide sequence encoding SRT. The term "noncoding region" refers to 5' and 3' sequences which flank the coding region that are not translated into amino acids also referred to as 5' and 3' untranslated regions).
Given the coding strand sequences encoding SRT disclosed herein the sequences set forth as odd-numbered SEQ ID NOs in the Sequence Listing), antisense nucleic acids of the invention can be designed according to the rules of Watson and Crick base pairing. The antisense nucleic acid molecule can be complementary to the entire coding region of SRT mRNA, but more preferably is an oligonucleotide which is antisense to only a portion of the coding or noncoding region of SRT mRNA. For example, the antisense oligonucleotide can be complementary to the region surrounding the translation start site of SRT mRNA. An antisense oligonucleotide can be, for example, about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50 nucleotides in length. An antisense nucleic acid of the invention can be constructed using chemical synthesis and enzymatic ligation reactions using procedures known in the art. For example, an antisense nucleic acid an antisense oligonucleotide) can be chemically synthesized using naturally occurring nucleotides or variously modified nucleotides designed to WO 01/00804 PCT/IB00/00922 increase the biological stability of the molecules or to increase the physical stability of the duplex formed between the antisense and sense nucleic acids, phosphorothioate derivatives and acridine substituted nucleotides can be used. Examples of modified nucleotides which can be used to generate the antisense nucleic acid include fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xanthine, 4acetylcytosine, 5-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyl-2thiouridine, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-Dgalactosylqueosine, inosine, N6-isopentenyladenine, I-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 3-methylcytosine, methylcytosine, N6-adenine, 7-methylguanine, 5-methylaminomethyluracil, methoxyaminomethyl-2-thiouracil, beta-D-mannosylqueosine, methoxycarboxymethyluracil, 5-methoxyuracil, 2-methylthio-N6-isopentenyladenine, acid wybutoxosine, pseudouracil, queosine, 2-thiocytosine, methyl-2-thiouracil, 2-thiouracil, 4-thiouracil, 5-methyluracil, uracil-5- oxyacetic acid methylester, uracil-5-oxyacetic acid 5-methyl-2-thiouracil, 3-(3-amino-3-N-2carboxypropyl) uracil, (acp3)w, and 2,6-diaminopurine. Alternatively, the antisense nucleic acid can be produced biologically using an expression vector into which a nucleic acid has been subcloned in an antisense orientation RNA transcribed from the inserted nucleic acid will be of an antisense orientation to a target nucleic acid of interest, described further in the following subsection).
The antisense nucleic acid molecules of the invention are typically administered to a cell or generated in situ such that they hybridize with or bind to cellular mRNA and/or genomic DNA encoding an SRT protein to thereby inhibit expression of the protein, by inhibiting transcription and/or translation. The hybridization can be by conventional nucleotide complementarity to form a stable duplex, or, for example, in the case of an antisense nucleic acid molecule which binds to DNA duplexes, through specific interactions in the major groove of the double helix. The antisense molecule can be modified such that it specifically binds to a receptor or an antigen expressed on a selected cell surface, by linking the antisense nucleic acid molecule to a peptide or an antibody which binds to a cell surface receptor or antigen. The antisense nucleic acid molecule can also be delivered to cells using the vectors described herein. To achieve sufficient intracellular concentrations of the antisense molecules, vector constructs in WO 01/00804 PCT/IB00/00922 -36which the antisense nucleic acid molecule is placed under the control of a strong prokaryotic, viral, or eukaryotic promoter are preferred.
In yet another embodiment, the antisense nucleic acid molecule of the invention is an a-anomeric nucleic acid molecule. An ot-anomeric nucleic acid molecule forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual p-units, the strands run parallel to each other (Gaultier et al. (1987) Nucleic Acids.
Res. 15:6625-6641). The antisense nucleic acid molecule can also comprise a 2'-omethylribonucleotide (Inoue et al. (1987) Nucleic Acids Res. 15:6131-6148) or a chimeric RNA-DNA analogue (Inoue et al. (1987) FEBS Lett. 215:327-330).
In still another embodiment, an antisense nucleic acid of the invention is a ribozyme. Ribozymes are catalytic RNA molecules with ribonuclease activity which are capable of cleaving a single-stranded nucleic acid, such as an mRNA, to which they have a complementary region. Thus, ribozymes hammerhead ribozymes (described in Haselhoff and Gerlach (1988) Nature 334:585-591)) can be used to catalytically cleave SRT mRNA transcripts to thereby inhibit translation of SRT mRNA.
A ribozyme having specificity for an SRT-encoding nucleic acid can be designed based upon the nucleotide sequence of an SRT cDNA disclosed herein SEQ ID NO: 119 (RXA00600)). For example, a derivative of a Tetrahymena L-19 IVS RNA can be constructed in which the nucleotide sequence of the active site is complementary to the nucleotide sequence to be cleaved in an SRT-encoding mRNA. See, Cech et al.
U.S. Patent No. 4,987,071 and Cech et al. U.S. Patent No. 5,116,742. Alternatively, SRT mRNA can be used to select a catalytic RNA having a specific ribonuclease activity from a pool of RNA molecules. See, Bartel, D. and Szostak, J.W. (1993) Science 261:1411-1418.
Alternatively, SRT gene expression can be inhibited by targeting nucleotide sequences complementary to the regulatory region of an SRT nucleotide sequence an SRT promoter and/or enhancers) to form triple helical structures that prevent transcription of an SRT gene in target cells. See generally, Helene, C. (1991) Anticancer Drug Des. 6(6):569-84; Helene, C. et al. (1992) Ann. N. Y Acad Sci. 660:27- 36; and Maher, L.J. (1992) Bioassays 14(12):807-15.
WO 01/00804 PCT/IB00/00922 -37- B. Recombinant Expression Vectors and Host Cells Another aspect of the invention pertains to vectors, preferably expression vectors, containing a nucleic acid encoding an SRT protein (or a portion thereof). As used herein, the term "vector" refers to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. One type of vector is a "plasmid", which refers to a circular double stranded DNA loop into which additional DNA segments can be ligated. Another type of vector is a viral vector, wherein additional DNA segments can be ligated into the viral genome. Certain vectors are capable of autonomous replication in a host cell into which they are introduced bacterial vectors having a bacterial origin of replication and episomal mammalian vectors). Other vectors non-episomal mammalian vectors) are integrated into the genome of a host cell upon introduction into the host cell, and thereby are replicated along with the host genome. Moreover, certain vectors are capable of directing the expression of genes to which they are operatively linked. Such vectors are referred to herein as "expression vectors". In general, expression vectors of utility in recombinant DNA techniques are often in the form ofplasmids. In the present specification, "plasmid" and "vector" can be used interchangeably as the plasmid is the most commonly used form of vector.
However, the invention is intended to include such other forms of expression vectors, such as viral vectors replication defective retroviruses, adenoviruses and adenoassociated viruses), which serve equivalent functions.
The recombinant expression vectors of the invention comprise a nucleic acid of the invention in a form suitable for expression of the nucleic acid in a host cell, which means that the recombinant expression vectors include one or more regulatory sequences, selected on the basis of the host cells to be used for expression, which is operatively linked to the nucleic acid sequence to be expressed. Within a recombinant expression vector, "operably linked" is intended to mean that the nucleotide sequence of interest is linked to the regulatory sequence(s) in a manner which allows for expression of the nucleotide sequence in an in vitro transcription/translation system or in a host cell when the vector is introduced into the host cell). The term "regulatory sequence" is intended to include promoters, enhancers and other expression control elements polyadenylation signals). Such regulatory sequences are described, for example, in Goeddel; Gene Expression Technology: Methods in Enzymology 185, WO 01/00804 PCT/IB00/00922 -38- Academic Press, San Diego, CA (1990). Regulatory sequences include those which direct constitutive expression of a nucleotide sequence in many types of host cell and those which direct expression of the nucleotide sequence only in certain host cells.
Preferred regulatory sequences are, for example, promoters such as cos-, tac-, trp-, tet-, trp-tet-, Ipp-, lac-, Ipp-lac-, lacl"-, T7-, T5-, T3-, gal-, trc-, ara-, SP6-, amy, SPO2, X-PRor X PL, which are used preferably in bacteria. Additional regulatory sequences are, for example, promoters from yeasts and fungi, such as ADC 1, MFa, AC, P-60, CYC1, GAPDH, TEF, rp28, ADH, promoters from plants such as CaMV/35S, SSU, OCS, lib4, usp, STLS1, B33, nos or ubiquitin- or phascolin-promoters. It is also possible to use artificial promoters. It will be appreciated by one of ordinary skill in the art that the design of the expression vector can depend on such factors as the choice of the host cell to be transformed, the level of expression of protein desired, etc. The expression vectors of the invention can be introduced into host cells to thereby produce proteins or peptides, including fusion proteins or peptides, encoded by nucleic acids as described herein SRT proteins, mutant forms of SRT proteins, fusion proteins, etc.).
The recombinant expression vectors of the invention can be designed for expression of SRT proteins in prokaryotic or eukaryotic cells. For example, SRT genes can be expressed in bacterial cells such as C. glutamicum, insect cells (using baculovirus expression vectors), yeast and other fungal cells (see Romanos, M.A. et al. (1992) "Foreign gene expression in yeast: a review", Yeast 8: 423-488; van den Hondel, C.A.M.J.J. et al. (1991) "Heterologous gene expression in filamentous fungi" in: More Gene Manipulations in Fungi, J.W. Bennet L.L. Lasure, eds., p. 396-428: Academic Press: San Diego; and van den Hondel, C.A.M.J.J. Punt, P.J. (1991) "Gene transfer systems and vector development for filamentous fungi, in: Applied Molecular Genetics of Fungi, Peberdy, J.F. et al., eds., p. 1-28, Cambridge University Press: Cambridge), algae and multicellular plant cells (see Schmidt, R. and Willmitzer, L. (1988) High efficiency Agrobacterium tumefaciens -mediated transformation of Arabidopsis thaliana leaf and cotyledon explants" Plant Cell Rep.: 583-586), or mammalian cells.
Suitable host cells are discussed further in Goeddel, Gene Expression Technology: Methods in Enzymology 185, Academic Press, San Diego, CA (1990). Alternatively, the recombinant expression vector can be transcribed and translated in vitro, for example using T7 promoter regulatory sequences and T7 polymerase.
WO 01/00804 PCT/IB00/00922 -39- Expression of proteins in prokaryotes is most often carried out with vectors containing constitutive or inducible promoters directing the expression of either fusion or non-fusion proteins. Fusion vectors add a number of amino acids to a protein encoded therein, usually to the amino terminus of the recombinant protein. Such fusion vectors typically serve three purposes: 1) to increase expression of recombinant protein; 2) to increase the solubility of the recombinant protein; and 3) to aid in the purification of the recombinant protein by acting as a ligand in affinity purification. Often, in fusion expression vectors, a proteolytic cleavage site is introduced at the junction of the fusion moiety and the recombinant protein to enable separation of the recombinant protein from the fusion moiety subsequent to purification of the fusion protein. Such enzymes, and their cognate recognition sequences, include Factor Xa, thrombin and enterokinase.
Typical fusion expression vectors include pGEX (Pharmacia Biotech Inc; Smith, D.B. and Johnson, K.S. (1988) Gene 67:31-40), pMAL (New England Biolabs, Beverly, MA) and pRIT5 (Pharmacia, Piscataway, NJ) which fuse glutathione S-transferase (GST), maltose E binding protein, or protein A, respectively, to the target recombinant protein. In one embodiment, the coding sequence of the SRT protein is cloned into a pGEX expression vector to create a vector encoding a fusion protein comprising, from the N-terminus to the C-terminus, GST-thrombin cleavage site-X protein. The fusion protein can be purified by affinity chromatography using glutathione-agarose resin.
Recombinant SRT protein unfused to GST can be recovered by cleavage of the fusion protein with thrombin.
Examples of suitable inducible non-fusion E. coli expression vectors include pTrc (Amann et al., (1988) Gene 69:301-315) pLG338, pACYC184, pBR322, pUC18, pUC 19, pKC30, pRep4, pHS pHS2, pPLc236, pMBL24, pLG200, pUR290, plN- II113-B 1, ?gtl 1, pBdCl, and pET 1 Id (Studier et al., Gene Expression Technology: Methods in Enzymology 185, Academic Press, San Diego, California (1990) 60-89; and Pouwels et al., eds. (1985) Cloning Vectors. Elsevier: New York IBSN 0 444 904018).
Target gene expression from the pTrc vector relies on host RNA polymerase transcription from a hybrid trp-lac fusion promoter. Target gene expression from the pET 1 Id vector relies on transcription from a T7 gnlO-lac fusion promoter mediated by a coexpressed viral RNA polymerase (T7 gnl). This viral polymerase is supplied by host strains BL21(DE3) or HMS 74(DE3) from a resident prophage harboring a T7 WO 01/00804 PCT/IB00/00922 gnl gene under the transcriptional control of the lacUV 5 promoter. For transformation of other varieties of bacteria, appropriate vectors may be selected. For example, the plasmids pIJ101, pIJ 3 64 pIJ702 and pIJ361 are known to be useful in transforming Streptomyces, while plasmids pUBI 10, pC194, or pBD214 are suited for transformation of Bacillus species. Several plasmids of use in the transfer of genetic information into Corynebacterium include pHM1519, pBLI, pSA77, or pAJ667 (Pouwels el al., eds.
(1985) Cloning Vectors. Elsevier: New York IBSN 0 444 904018).
One strategy to maximize recombinant protein expression is to express the protein in a host bacteria with an impaired capacity to proteolytically cleave the recombinant protein (Gottesman, Gene Expression Technology: Methods in Enzymology 185, Academic Press, San Diego, California (1990) 119-128). Another strategy is to alter the nucleic acid sequence of the nucleic acid to be inserted into an expression vector so that the individual codons for each amino acid are those preferentially utilized in the bacterium chosen for expression, such as C. glutamicum (Wada el al. (1992) Nucleic Acids Res. 20:2111-2118). Such alteration of nucleic acid sequences of the invention can be carried out by standard DNA synthesis techniques.
In another embodiment, the SRT protein expression vector is a yeast expression vector. Examples of vectors for expression in yeast S. cerevisiae include pYepSecl (Baldari, et al., (1987) Embo J. 6:229-234), 2 u, pAG-1, Yep6, Yepl3, pEMBLYe23, pMFa (Kurjan and Herskowitz, (1982) Cell 30:933-943), pJRY88 (Schultz et al., (1987) Gene 54:113-123), and pYES2 (Invitrogen Corporation, San Diego, CA). Vectors and methods for the construction of vectors appropriate for use in other fungi, such as the filamentous fungi, include those detailed in: van den Hondel, C.A.M.J.J. Punt, P.J.
(1991) "Gene transfer systems and vector development for filamentous fungi, in: Applied Molecular Genetics of Fungi, J.F. Peberdy, et al., eds., p. 1-28, Cambridge University Press: Cambridge, and Pouwels et al., eds. (1985) Cloning Vectors. Elsevier: New York (IBSN 0 444 904018).
Alternatively, the SRT proteins of the invention can be expressed in insect cells using baculovirus expression vectors. Baculovirus vectors available for expression of proteins in cultured insect cells Sf9 cells) include the pAc series (Smith et al.
(1983) Mol. Cell Biol. 3:2156-2165) and the pVL series (Lucklow and Summers (1989) Virology 170:31-39).
WO 01/00804 PCT/IB00/00922 -41 In another embodiment, the SRT proteins of the invention may be expressed in unicellular plant cells (such as algae) or in plant cells from higher plants the spermatophytes, such as crop plants). Examples of plant expression vectors include those detailed in: Becker, Kemper, Schell, J. and Masterson, R. (1992) "New plant binary vectors with selectable markers located proximal to the left border", Plant Mol. Biol. 20: 1195-1197; and Bevan, M.W. (1984) "Binary Agrobacterium vectors for plant transformation", Nucl. Acid. Res. 12: 8711-8721, and include pLGV23, pGHlac+, pBIN19, pAK2004, and pDH51 (Pouwels et al., eds. (1985) Cloning Vectors. Elsevier: New York IBSN 0 444 904018).
In yet another embodiment, a nucleic acid of the invention is expressed in mammalian cells using a mammalian expression vector. Examples of mammalian expression vectors include pCDM8 (Seed, B. (1987) Nature 329:840) and pMT2PC (Kaufman et al. (1987) EMBOJ. 6:187-195). When used in mammalian cells, the expression vector's control functions are often provided by viral regulatory elements.
For example, commonly used promoters are derived from polyoma, Adenovirus 2, cytomegalovirus and Simian Virus 40. For other suitable expression systems for both prokaryotic and eukaryotic cells see chapters 16 and 17 of Sambrook, Fritsh, E. F., and Maniatis, T. Molecular Cloning: A Laboratory Manual. 2nd, ed, Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1989.
In another embodiment, the recombinant mammalian expression vector is capable of directing expression of the nucleic acid preferentially in a particular cell type tissue-specific regulatory elements are used to express the nucleic acid). Tissuespecific regulatory elements are known in the art. Non-limiting examples of suitable tissue-specific promoters include the albumin promoter (liver-specific; Pinkert et al.
(1987) Genes Dev. 1:268-277), lymphoid-specific promoters (Calame and Eaton (1988) Adv. Immunol. 43:235-275), in particular promoters of T cell receptors (Winoto and Baltimore (1989) EMBO J 8:729-733) and immunoglobulins (Banerji et al. (1983) Cell 33:729-740; Queen and Baltimore (1983) Cell 33:741-748), neuron-specific promoters the neurofilament promoter; Byrne and Ruddle (1989) PNAS 86:5473-5477), pancreas-specific promoters (Edlund et al. (1985) Science 230:912-916), and mammary gland-specific promoters milk whey promoter; U.S. Patent No. 4,873,316 and WO 01/00804 PCT/IB00/00922 -42- European Application Publication No. 264,166). Developmentally-regulated promoters are also encompassed, for example the murine hox promoters (Kessel and Gruss (1990) Science 249:374-379) and the a-fetoprotein promoter (Campes and Tilghman (1989) Genes Dev. 3:537-546).
The invention further provides a recombinant expression vector comprising a DNA molecule of the invention cloned into the expression vector in an antisense orientation. That is, the DNA molecule is operatively linked to a regulatory sequence in a manner which allows for expression (by transcription of the DNA molecule) of an RNA molecule which is antisense to SRT mRNA. Regulatory sequences operatively linked to a nucleic acid cloned in the antisense orientation can be chosen which direct the continuous expression of the antisense RNA molecule in a variety of cell types, for instance viral promoters and/or enhancers, or regulatory sequences can be chosen which direct constitutive, tissue specific or cell type specific expression of antisense RNA.
The antisense expression vector can be in the form of a recombinant plasmid, phagemid or attenuated virus in which antisense nucleic acids are produced under the control of a high efficiency regulatory region, the activity of which can be determined by the cell type into which the vector is introduced. For a discussion of the regulation of gene expression using antisense genes see Weintraub, H. et al., Antisense RNA as a molecular tool for genetic analysis, Reviews Trends in Genetics, Vol. 1(1) 1986.
Another aspect of the invention pertains to host cells into which a recombinant expression vector of the invention has been introduced. The terms "host cell" and "recombinant host cell" are used interchangeably herein. It is understood that such terms refer not only to the particular subject cell but to the progeny or potential progeny of such a cell. Because certain modifications may occur in succeeding generations due to either mutation or environmental influences, such progeny may not, in fact, be identical to the parent cell, but are still included within the scope of the term as used herein.
A host cell can be any prokaryotic or eukaryotic cell. For example, an SRT protein can be expressed in bacterial cells such as C. glutamicum, insect cells, yeast or mammalian cells (such as Chinese hamster ovary cells (CHO) or COS cells). Other suitable host cells are known to those of ordinary skill in the art. Microorganisms related WO 01/00804 PCT/IB00/00922 -43to Corynebacterium glutamicum which may be conveniently used as host cells for the nucleic acid and protein molecules of the invention are set forth in Table 3.
Vector DNA can be introduced into prokaryotic or eukaryotic cells via conventional transformation or transfection techniques. As used herein, the terms "transformation" and "transfection" are intended to refer to a variety of art-recognized techniques for introducing foreign nucleic acid linear DNA or RNA a linearized vector or a gene construct alone without a vector) or nucleic acid in the form of a vector a plasmid, phage, phasmid, phagemid, transposon or other DNA)) into a host cell, including calcium phosphate or calcium chloride co-precipitation, DEAEdextran-mediated transfection, lipofection, or electroporation. Suitable methods for transforming or transfecting host cells can be found in Sambrook, et al. (Molecular Cloning: A Laboratory Manual. 2nd, ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1989), and other laboratory manuals.
For stable transfection of mammalian cells, it is known that, depending upon the expression vector and transfection technique used, only a small fraction of cells may integrate the foreign DNA into their genome. In order to identify and select these integrants, a gene that encodes a selectable marker resistance to antibiotics) is generally introduced into the host cells along with the gene of interest. Preferred selectable markers include those which confer resistance to drugs, such as G418, hygromycin and methotrexate. Nucleic acid encoding a selectable marker can be introduced into a host cell on the same vector as that encoding an SRT protein or can be introduced on a separate vector. Cells stably transfected with the introduced nucleic acid can be identified by drug selection cells that have incorporated the selectable marker gene will survive, while the other cells die).
To create a homologous recombinant microorganism, a vector is prepared which contains at least a portion of an SRT gene into which a deletion, addition or substitution has been introduced to thereby alter, functionally disrupt, the SRT gene.
Preferably, this SRT gene is a Corynebacterium glutamicum SRT gene, but it can be a homologue from a related bacterium or even from a mammalian, yeast, or insect source.
In a preferred embodiment, the vector is designed such that, upon homologous recombination, the endogenous SRT gene is functionally disrupted no longer encodes a functional protein; also referred to as a "knock out" vector). Alternatively, WO 01/00804 PCT/IB00/00922 -44the vector can be designed such that, upon homologous recombination, the endogenous SRT gene is mutated or otherwise altered but still encodes functional protein the upstream regulatory region can be altered to thereby alter the expression of the endogenous SRT protein). In the homologous recombination vector, the altered portion of the SRT gene is flanked at its 5' and 3' ends by additional nucleic acid of the SRT gene to allow for homologous recombination to occur between the exogenous SRT gene carried by the vector and an endogenous SRT gene in a microorganism. The additional flanking SRT nucleic acid is of sufficient length for successful homologous recombination with the endogenous gene. Typically, several kilobases of flanking DNA (both at the 5' and 3' ends) are included in the vector (see Thomas, and Capecchi, M.R. (1987) Cell 51: 503 for a description of homologous recombination vectors). The vector is introduced into a microorganism by electroporation) and cells in which the introduced SRT gene has homologously recombined with the endogenous SRT gene are selected, using art-known techniques.
In another embodiment, recombinant microorganisms can be produced which contain selected systems which allow for regulated expression of the introduced gene.
For example, inclusion of an SRT gene on a vector placing it under control of the lac operon permits expression of the SRT gene only in the presence of IPTG. Such regulatory systems are well known in the art.
In another embodiment, an endogenous SRT gene in a host cell is disrupted by homologous recombination or other genetic means known in the art) such that expression of its protein product does not occur. In another embodiment, an endogenous or introduced SRT gene in a host cell has been altered by one or more point mutations, deletions, or inversions, but still encodes a functional SRT protein. In still another embodiment, one or more of the regulatory regions a promoter, repressor, or inducer) of an SRT gene in a microorganism has been altered by deletion, truncation, inversion, or point mutation) such that the expression of the SRT gene is modulated. One of ordinary skill in the art will appreciate that host cells containing more than one of the described SRT gene and protein modifications may be readily produced using the methods of the invention, and are meant to be included in the present invention.
WO 01/00804 PCT/IB00/00922 A host cell of the invention, such as a prokaryotic or eukaryotic host cell in culture, can be used to produce express) an SRT protein. Accordingly, the invention further provides methods for producing SRT proteins using the host cells of the invention. In one embodiment, the method comprises culturing the host cell of invention (into which a recombinant expression vector encoding an SRT protein has been introduced, or into which genome has been introduced a gene encoding a wild-type or altered SRT protein) in a suitable medium until SRT protein is produced. In another embodiment, the method further comprises isolating SRT proteins from the medium or the host cell.
C. Isolated SRT Proteins Another aspect of the invention pertains to isolated SRI proteins, and biologically active portions thereof. An "isolated" or "purified" protein or biologically active portion thereof is substantially free of cellular material when produced by recombinant DNA techniques, or chemical precursors or other chemicals when chemically synthesized. The language "substantially free of cellular material" includes preparations of SRT protein in which the protein is separated from cellular components of the cells in which it is naturally or recombinantly produced. In one embodiment, the language "substantially free of cellular material" includes preparations of SRT protein having less than about 30% (by dry weight) of non-SRT protein (also referred to herein as a "contaminating protein"), more preferably less than about 20% of non-SRT protein, still more preferably less than about 10% of non-SRT protein, and most preferably less than about 5% non-SRT protein. When the SRT protein or biologically active portion thereof is recombinantly produced, it is also preferably substantially free of culture medium, culture medium represents less than about 20%, more preferably less than about 10%, and most preferably less than about 5% of the volume of the protein preparation. The language "substantially free of chemical precursors or other chemicals" includes preparations of SRT protein in which the protein is separated from chemical precursors or other chemicals which are involved in the synthesis of the protein. In one embodiment, the language "substantially free of chemical precursors or other chemicals" includes preparations of SRT protein having less than about 30% (by dry weight) of chemical precursors or non-SRT chemicals, more preferably less than WO 01/00804 PCT/IB00/00922 -46about 20% chemical precursors or non-SRT chemicals, still more preferably less than about 10% chemical precursors or non-SRT chemicals, and most preferably less than about 5% chemical precursors or non-SRT chemicals. In preferred embodiments, isolated proteins or biologically active portions thereof lack contaminating proteins from the same organism from which the SRT protein is derived. Typically, such proteins are produced by recombinant expression of, for example, a C glutamicum SRT protein in a microorganism such as C. glutamicum.
An isolated SRT protein or a portion thereof of the invention can contribute to the resistance or tolerance of C. glutamicum to one or more chemical or environmental stresses or hazards, or has one or more of the activities set forth in Table 1. In preferred embodiments, the protein or portion thereof comprises an amino acid sequence which is sufficiently homologous to an amino acid sequence of the invention a sequence of an even-numbered SEQ ID NO: of the Sequence Listing) such that the protein or portion thereof maintains the ability to mediate the resistance or tolerance of C. glutamicum to one or more chemical or environmental stresses or hazards. The portion of the protein is preferably a biologically active portion as described herein. In another preferred embodiment, an SRT protein of the invention has an amino acid sequence set forth as an even-numbered SEQ ID NO: of the Sequence Listing. In yet another preferred embodiment, the SRT protein has an amino acid sequence which is encoded by a nucleotide sequence which hybridizes, hybridizes under stringent conditions, to a nucleotide sequence of the invention a sequence of an odd-numbered SEQ ID NO: of the Sequence Listing). In still another preferred embodiment, the SRT protein has an amino acid sequence which is encoded by a nucleotide sequence that is at least about 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, or 60%, preferably at least about 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, or 70%, more preferably at least about 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, or 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, or 90%, or 91%, 92%, 93%, 94%, and even more preferably at least about 95%, 96%, 97%, 98%, 99% or more homologous to one of the nucleic acid sequences of the invention or a portion thereof. Ranges and identity values intermediate to the above-recited values, 70-90% identical or 80-95% identical) are also intended to be encompassed by the present invention. For example, ranges of identity values using a combination of any of the above values recited as upper WO 01/00804 PCT/IBOO/00922 -47and/or lower limits are intended to be included. The preferred SRT proteins of the present invention also preferably possess at least one of the SRT activities described herein. For example, a preferred SRT protein of the present invention includes an amino acid sequence encoded by a nucleotide sequence which hybridizes, hybridizes under stringent conditions, to a nucleotide sequence of the invention, and which can increase the resistance or tolerance of C. glutamicum to one or more environmental or chemical stresses, or which has one or more of the activities set forth in Table 1.
In other embodiments, the SRT protein is substantially homologous to an amino acid sequence of the invention a sequence of an even-numbered SEQ ID NO: of the Sequence Listing) and retains the functional activity of the protein of one of the amino acid sequences of the invention yet differs in amino acid sequence due to natural variation or mutagenesis, as described in detail in subsection I above. Accordingly, in another embodiment, the SRT protein is a protein which comprises an amino acid sequence which is at least about 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, or 60%, preferably at least about 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, or 70%, more preferably at least about 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, or 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, or 90%, or 91%, 92%, 93%, 94%, and even more preferably at least about 95%, 96%, 97%, 98%, 99% or more homologous to an entire amino acid sequence of the invention and which has at least one of the SRT activities described herein. Ranges and identity values intermediate to the above-recited values, 70-90% identical or 80-95% identical) are also intended to be encompassed by the present invention. For example, ranges of identity values using a combination of any of the above values recited as upper and/or lower limits are intended to be included. In another embodiment, the invention pertains to a full length C. glutamicum protein which is substantially homologous to an entire amino acid sequence of the invention.
Biologically active portions of an SRT protein include peptides comprising amino acid sequences derived from the amino acid sequence of an SRT protein, an amino acid sequence of an even-numbered SEQ ID NO: of the Sequence Listing or the amino acid sequence of a protein homologous to an SRT protein, which include fewer amino acids than a full length SRT protein or the full length protein which is homologous to an SRT protein, and exhibit at least one activity of an SRT protein.
WO 01/00804 PCT/IB00/00922 -48- Typically, biologically active portions (peptides, peptides which are, for example, 10, 15, 20, 30, 35, 36, 37, 38, 39, 40, 50, 100 or more amino acids in length) comprise a domain or motif with at least one activity of an SRT protein. Moreover, other biologically active portions, in which other regions of the protein are deleted, can be prepared by recombinant techniques and evaluated for one or more of the activities described herein. Preferably, the biologically active portions of an SRT protein include one or more selected domains/motifs or portions thereof having biological activity.
SRT proteins are preferably produced by recombinant DNA techniques. For example, a nucleic acid molecule encoding the protein is cloned into an expression vector (as described above), the expression vector is introduced into a host cell (as described above) and the SRT protein is expressed in the host cell. The SRT protein can then be isolated from the cells by an appropriate purification scheme using standard protein purification techniques. Alternative to recombinant expression, an SRT protein, polypeptide, or peptide can be synthesized chemically using standard peptide synthesis techniques. Moreover, native SRT protein can be isolated from cells endothelial cells), for example using an anti-SRT antibody, which can be produced by standard techniques utilizing an SRT protein or fragment thereof of this invention.
The invention also provides SRT chimeric or fusion proteins. As used herein, an SRT "chimeric protein" or "fusion protein" comprises an SRT polypeptide operatively linked to a non-SRT polypeptide. An "SRT polypeptide" refers to a polypeptide having an amino acid sequence corresponding to SRT, whereas a "non-SRT polypeptide" refers to a polypeptide having an amino acid sequence corresponding to a protein which is not substantially homologous to the SRT protein, a protein which is different from the SRT protein and which is derived from the same or a different organism. Within the fusion protein, the term "operatively linked" is intended to indicate that the SRT polypeptide and the non-SRT polypeptide are fused in-frame to each other. The non- SRT polypeptide can be fused to the N-terminus or C-terminus of the SRT polypeptide.
For example, in one embodiment the fusion protein is a GST-SRT fusion protein in which the SRT sequences are fused to the C-terminus of the GST sequences. Such fusion proteins can facilitate the purification of recombinant SRT proteins. In another embodiment, the fusion protein is an SRT protein containing a heterologous signal sequence at its N-terminus. In certain host cells mammalian host cells), expression WO 01/00804 PCT/IB00/00922 -49and/or secretion of an SRT protein can be increased through use of a heterologous signal sequence.
Preferably, an SRT chimeric or fusion protein of the invention is produced by standard recombinant DNA techniques. For example, DNA fragments coding for the different polypeptide sequences are ligated together in-frame in accordance with conventional techniques, for example by employing blunt-ended or stagger-ended termini for ligation, restriction enzyme digestion to provide for appropriate termini, filling-in of cohesive ends as appropriate, alkaline phosphatase treatment to avoid undesirable joining, and enzymatic ligation. In another embodiment, the fusion gene can be synthesized by conventional techniques including automated DNA synthesizers.
Alternatively, PCR amplification of gene fragments can be carried out using anchor primers which give rise to complementary overhangs between two consecutive gene fragments which can subsequently be annealed and reamplified to generate a chimeric gene sequence (see, for example, Current Protocols in Molecular Biology, eds. Ausubel et al. John Wiley Sons: 1992). Moreover, many expression vectors are commercially available that already encode a fusion moiety a GST polypeptide). An SRTencoding nucleic acid can be cloned into such an expression vector such that the fusion moiety is linked in-frame to the SRT protein.
Homologues of the SRT protein can be generated by mutagenesis, discrete point mutation or truncation of the SRT protein. As used herein, the term "homologue" refers to a variant form of the SRT protein which acts as an agonist or antagonist of the activity of the SRT protein. An agonist of the SRT protein can retain substantially the same, or a subset, of the biological activities of the SRT protein. An antagonist of the SRT protein can inhibit one or more of the activities of the naturally occurring form of the SRT protein, by, for example, competitively binding to a downstream or upstream member of the SRT system which includes the SRT protein. Thus, the C. glutamicum SRT protein and homologues thereof of the present invention may increase the tolerance or resistance ofC. glutamicum to one or more chemical or environmental stresses.
In an alternative embodiment, homologues of the SRT protein can be identified by screening combinatorial libraries of mutants, truncation mutants, of the SRT protein for SRT protein agonist or antagonist activity. In one embodiment, a variegated library of SRT variants is generated by combinatorial mutagenesis at the nucleic acid WO 01/00804 PCT/IB00/00922 level and is encoded by a variegated gene library. A variegated library of SRT variants can be produced by, for example, enzymatically ligating a mixture of synthetic oligonucleotides into gene sequences such that a degenerate set of potential SRT sequences is expressible as individual polypeptides, or alternatively, as a set of larger fusion proteins for phage display) containing the set of SRT sequences therein.
There are a variety of methods which can be used to produce libraries of potential SRT homologues from a degenerate oligonucleotide sequence. Chemical synthesis of a degenerate gene sequence can be performed in an automatic DNA synthesizer, and the synthetic gene then ligated into an appropriate expression vector. Use of a degenerate set of genes allows for the provision, in one mixture, of all of the sequences encoding the desired set of potential SRT sequences. Methods for synthesizing degenerate oligonucleotides are known in the art (see, Narang, S.A. (1983) Tetrahedron 39:3; Itakura et al. (1984) Annu. Rev. Biochem. 53:323; Itakura el al. (1984) Science 198:1056; Ike et al. (1983) Nucleic Acid Res. 11:477.
In addition, libraries of fragments of the SRT protein coding can be used to generate a variegated population of SRT fragments for screening and subsequent selection of homologucs of an SRT protein. In one embodiment, a library of coding sequence fragments can be generated by treating a double stranded PCR fragment of an SRT coding sequence with a nuclease under conditions wherein nicking occurs only about once per molecule, denaturing the double stranded DNA, renaturing the DNA to form double stranded DNA which can include sense/antisense pairs from different nicked products, removing single stranded portions from reformed duplexes by treatment with S nuclease, and ligating the resulting fragment library into an expression vector. By this method, an expression library can be derived which encodes N-terminal, C-terminal and internal fragments of various sizes of the SRT protein.
Several techniques are known in the art for screening gene products of combinatorial libraries made by point mutations or truncation, and for screening cDNA libraries for gene products having a selected property. Such techniques are adaptable for rapid screening of the gene libraries generated by the combinatorial mutagenesis of SRT homologues. The most widely used techniques, which are amenable to high through-put analysis, for screening large gene libraries typically include cloning the gene library into replicable expression vectors, transforming appropriate cells with the resulting library of WO 01/00804 PCT/IB00/00922 -51vectors, and expressing the combinatorial genes under conditions in which detection of a desired activity facilitates isolation of the vector encoding the gene whose product was detected. Recursive ensemble mutagenesis (REM), a new technique which enhances the frequency of functional mutants in the libraries, can be used in combination with the screening assays to identify SRT homologues (Arkin and Yourvan (1992) PNAS 89:7811-7815; Delgrave et al (1993) Protein Engineering 6(3):327-331).
In another embodiment, cell based assays can be exploited to analyze a variegated SRT library, using methods well known in the art.
D. Uses and Methods of the Invention The nucleic acid molecules, proteins, protein homologues, fusion proteins, primers, vectors, and host cells described herein can be used in one or more of the following methods: identification of C. glutamicum and related organisms; mapping of genomes of organisms related to C. glutamicum; identification and localization of C.
glutamicum sequences of interest; evolutionary studies; determination of SRT protein regions required for function; modulation of an SRT protein activity; modulation of the activity of an SRT pathway; and modulation of cellular production of a desired compound, such as a fine chemical.
The SRT nucleic acid molecules of the invention have a variety of uses. First, they may be used to identify an organism as being Corynebacterium glutamicum or a close relative thereof. Also, they may be used to identify the presence of C. glutamicum or a relative thereof in a mixed population of microorganisms. The invention provides the nucleic acid sequences of a number of C glutamicum genes; by probing the extracted genomic DNA of a culture of a unique or mixed population of microorganisms under stringent conditions with a probe spanning a region of a C. glutamicum gene which is unique to this organism, one can ascertain whether this organism is present.
Although Corynebacterium glutamicum itself is nonpathogenic, it is related to pathogenic species, such as Corynebacterium diphtheriae. Corynebacterium diphtheriae is the causative agent of diphtheria, a rapidly developing, acute, febrile infection which involves both local and systemic pathology. In this disease, a local lesion develops in the upper respiratory tract and involves necrotic injury to epithelial cells; the bacilli secrete toxin which is disseminated through this lesion to distal susceptible tissues of the WO 01/00804 PCT/IB00/00922 -52body. Degenerative changes brought about by the inhibition of protein synthesis in these tissues, which include heart, muscle, peripheral nerves, adrenals, kidneys, liver and spleen, result in the systemic pathology of the disease. Diphtheria continues to have high incidence in many parts of the world, including Africa, Asia, Eastern Europe and the independent states of the former Soviet Union. An ongoing epidemic of diphtheria in the latter two regions has resulted in at least 5,000 deaths since 1990.
In one embodiment, the invention provides a method of identifying the presence or activity of Cornyebacterium diphtheriae in a subject. This method includes detection of one or more of the nucleic acid or amino acid sequences of the invention the sequences set forth as odd-numbered or even-numbered SEQ ID NOs, respectively, in the Sequence Listing) in a subject, thereby detecting the presence or activity of Corynehucterium diphtheriue in the subject. C. glutamicum and C. diphtheriae are related bacteria, and many of the nucleic acid and protein molecules in C. glutamicum are homologous to C. diphtheriae nucleic acid and protein molecules, and can therefore be used to detect C diphtheriae in a subject.
The nucleic acid and protein molecules of the invention may also serve as markers for specific regions of the genome. This has utility not only in the mapping of the genome, but also for functional studies of C. glutamicum proteins. For example, to identify the region of the genome to which a particular C. glutamicum DNA-binding protein binds, the C. glutamicum genome could be digested, and the fragments incubated with the DNA-binding protein. Those which bind the protein may be additionally probed with the nucleic acid molecules of the invention, preferably with readily detectable labels; binding of such a nucleic acid molecule to the genome fragment enables the localization of the fragment to the genome map of C. glutamicum, and, when performed multiple times with different enzymes, facilitates a rapid determination of the nucleic acid sequence to which the protein binds. Further, the nucleic acid molecules of the invention may be sufficiently homologous to the sequences of related species such that these nucleic acid molecules may serve as markers for the construction of a genomic map in related bacteria, such as Brevibacterium lactofermentum.
The SRT nucleic acid molecules of the invention are also useful for evolutionary and protein structural studies. The resistance processes in which the molecules of the invention participate are utilized by a wide variety of cells; by comparing the sequences WO 01/00804 PCT/IB00/00922 -53 of the nucleic acid molecules of the present invention to those encoding similar enzymes from other organisms, the evolutionary relatedness of the organisms can be assessed.
Similarly, such a comparison permits an assessment of which regions of the sequence are conserved and which are not, which may aid in determining those regions of the protein which are essential for the functioning of the enzyme. This type of determination is of value for protein engineering studies and may give an indication of what the protein can tolerate in terms of mutagenesis without losing function.
The genes of the invention, eg., the gene encoding LMRB (SEQ ID NO:1) or other gene of the invention encoding a chemical or environmental resistance or tolerance protein resistance against one or more antibiotics), may be used as genetic markers for the genetic transformation of the transfer of additional genes into or disruption of preexisting genes of) organisms such as C glutamicum or other bacterial species.
Use of these nucleic acid molecules permits efficient selection of organisms which have incorporated a given transgene cassette a plasmid, phage, phasmid, phagemid, transposon, or other nucleic acid element), based on a trait which permits the survival of the organism in an otherwise hostile or toxic environment in the presence of an antimicrobial compound). By employing one or more of the genes of the invention as genetic markers, the speed and ease with which organisms having desirable transformed traits modulated fine chemical production) are engineered and isolated are improved. While it is advantageous to use the genes of the invention for selection of transformed C glulamicum and related bacteria, it is possible, as described herein, to use homologs homologs from other organisms), allelic variants or fragments of the gene retaining desired activity. Furthermore, 5' and 3' regulatory elements of the genes of the invention may be modified as described herein by nucleotide substitution, insertion, deletion, or replacement with a more desirable genetic element) to modulate the transcription of the gene. For example, an LMRB variant in which the nucleotide sequence in the region from -1 to -200 5' to the start codon has been altered to modulate (preferably increase) the transcription and/or translation of LMRB may be employed, as can constructs in which a gene of the invention the LMRB gene (SEQ ID NO:1)) is functionally coupled to one or more regulatory signals inducer or repressor binding sequences) which can be used for modulating gene expression.
WO 01/00804 PCT/IB00/00922 -54- Similarly, more than one copy of a gene (functional or inactivated) of the invention may be employed.
An additional application of the genes of the invention the gene encoding LMRB (SEQ ID NO: 1) or other drug- or antibiotic-resistance gene) is in the discovery of new antibiotics which are active against Corynebacteria and/or other bacteria. For example, a gene of the invention may be expressed (or overexpressed) in a suitable host to generate an organism with increased resistance to one or more drugs or antibiotics (in the case of LMRB, lincosamides in particular, especially lincomycin). This type of resistant host can subsequently be used to screen for chemicals with bacteriostatic and/or bacteriocidal activity, such as novel antibiotic compounds. It is possible, in particular, to use the genes of the invention the LMRB gene) to identify new antibiotics which are active against those microorganisms which are already resistant to standard antibiotic compounds.
The invention provides methods for screening molecules which modulate the activity of an SRT protein, either by interacting with the protein itself or a substrate or binding partner of the SRT protein, or by modulating the transcription or translation of.f SRT nucleic acid molecule of the invention. In such methods, a microorganism expressing one or more SRT proteins of the invention is contacted with one or more test compounds, and the effect of each test compound on the activity or level of expression of the SRT protein is assessed.
Manipulation of the SRT nucleic acid molecules of the invention may result in the production of SRT proteins having functional differences from the wild-type SRT proteins. These proteins may be improved in efficiency or activity, may be present in greater numbers in the cell than is usual, or may be decreased in efficiency or activity.
The goal of such manipulations is to increase the viability and activity of the cell when the cell is exposed to the environmental and chemical stresses and hazards which frequently accompany large-scale fermentative culture. Thus, by increasing the activity or copy number of a heat-shock-regulated protease, one may increase the ability of the cell to destroy incorrectly folded proteins, which may otherwise interfere with normal cellular functioning (for example, by continuing to bind substrates or cofactors although the protein lacks the activity to act on these molecules appropriately). The same is true for the overexpression or optimization of activity of one or more chaperone molecules WO 01/00804 PCT/IB00/00922 induced by heat or cold shock. These proteins aid in the correct folding of nascent polypeptide chains, and thus their increased activity or presence should increase the percentage of correctly folded proteins in the cell, which in turn should increase the overall metabolic efficiency and viability of the cells in culture. The overexpression or optimization of the transporter molecules activated by osmotic shock should result in an increased ability on the part of the cell to maintain intracellular homeostasis, thereby increasing the viability of these cells in culture. Similarly, the overproduction or increase in activity by mutagenesis of proteins involved in the development of cellular resistance to chemical stresses of various kinds (either by transport of the offending chemical out of the cell or by modification of the chemical to a less hazardous substance) should increase the fitness of the organism in the environment containing the hazardous substance large-scale fermentative culture), and thereby may permit relatively larger numbers of cells to survive in such a culture. The net effect of all of these mutagenesis strategies is to increase the quantity of fine-chemical-producing compounds in the culture, thereby increasing the yield, production, and/or efficiency of production of one or more desired fine chemicals from the culture.
This aforementioned list of mutagenesis strategies for SRT proteins to result in increased yields of a desired compound is not meant to be limiting; variations on these mutagenesis strategies will be readily apparent to one of ordinary skill in the art. By these mechanisms, the nucleic acid and protein molecules of the invention may be utilized to generate C. glutamicum or related strains of bacteria expressing mutated SRT nucleic acid and protein molecules such that the yield, production, and/or efficiency of production of a desired compound is improved. This desired compound may be any natural product of C. glutamicum, which includes the final products of biosynthesis pathways and intermediates of naturally-occurring metabolic pathways, as well as molecules which do not naturally occur in the metabolism of C glutamicum, but which are produced by a C. glutamicum strain of the invention.
This invention is further illustrated by the following examples which should not be construed as limiting. The contents of all references, patent applications, patents, published patent applications, Tables, and the sequence listing cited throughout this application are hereby incorporated by reference.
TABLE 1: Genes Included in the Application Nucleic Acid Amino Acid Identification Code Contig NT Start NT Stop Function SEQ ID NO SECI ID NO 1 2 RXA01524 GROD424 29041 30483 Lincomycine RESISTANCE PROTEIN 3 4 RXA00497 GROD0124 52 348 10 KIDCHAPERONIN 6 RXN00493 W00D86 14389 16002 60 KO CHAPERONIN 7 8 F RXA00498 GR001 24 363 1601 60 KD CHAPERONIN 9 10 RXA01217 GR00353 802 203 GENERAL STRESS PROTEIN CTC 11 12 RXA00605 GR001 59 7412 5865 CATALASE (EC 1.11. 16) 13 14 RXA00404 GROO089 2909 594 CARBON STARVATION PROTEIN A 16 RXN03119 WV0098 86877 87008 SUPEROXIDE DISMUTASE [MN) (EC 1.15.1.1) 17 18 RXN03120 WV0098 87351 87476 SUPEROXIDE DISMUTASE (MN] (EC 1.15.1.1) 19 20 RXN00575 WV0323 14716 15252 PHOSPHINOTHRICIN-RESISTANCE PROTEIN 21 22 F RXA00575 GRO01 56 2130 1648 PHOSPHINOTHRICIN-RESISTANCE PROTEIN Chaperones Nucleic Acid Amino Acid Identification Code SEQ ID NO SEQ I1D NO 23 24 RXN01 345 26 F RXA01345 27 28 RXA02541 29 30 RXA02542 31 32 RXN02543 33 34 F RXA02543 36 RXN02280 37 38 IF RXA02282 39 40 RXA00886 41 42 RXS00568 43 44 RXN03038 46 RXN03039 47 48 RXN03040 49 50 RXN0305I 51 52 RXN03054 53 54 RXN02949 56 RXN02462 57 58 RXN01 559 59 60 RXN00046 61 62 RXN01863 63 64 RXN00833 Contig NT Star NT Stop Function VV0123 4883 3.432 Moleculares chraperon (I-SP70IDnaK family) GR00391 1172 6 Molecular chaperones (HSP70/DnaK family) GR00726 13657 12473 DNAJ PROTEIN GR00726 14518 13865 GRIPE PROTEIN WV0057 22031 20178 ONAK PROTEIN GR00726 16375 14522 ONAK PROTEIN W0O152 1849 26 TRAPI GR00659 1145 1480 Molecular chaperone, HSP90 family GR00242 12396 135,41 DNAJ PROTEIN WV0251 2928 1582 TRIGGER FACTOR WV0017 42941 43666 PSI PROTEIN VORLAUFER WVODl8 2 631 PSI PROTEIN VORLAUIFER W00O18 761 1069 PSI PROTEIN VORLAUIFER W0022 2832 3566 PSi PROTEIN VORI.AUFER W0026 1906 3486 PSI PROTEIN VORLAUIFER W0025 31243 31575 PREPROTEIN TRANSLOKASE SECE UNTEREINHEIT W0124 11932 13749 PREPROTEIN TRANSLOKASE SECA UNTEREINHEIT WV01171 7795 5954 PROTEIN-EXPORT MEMBRANE PROTEIN SECO WV01119 5363 6058 Signal Erlkennung particle GTPase W0206 1172 24 10/C Thioredoxin-Ahnliche oxidoreductase WV0180 8039 8533 THIOL PEROXIDASE (EC 1.11.1..) Table I (continued) Nucleic Acid Amino Acid Identification Code Contig NT Start NT Stop Function SEQ ID NO SEQ I1D NO 66 RXN01 676 WV0 179 12059 11304 THIOL:DISULFIDE AUSTAUSCH PROTEIN 0580 87 68 RXN00380 WV0223 836 216 THIOL:DISULFIDE AUSTAUSCH PROTEIN TLPA 69 70 RXN00937 W0079 42335 42706 THIOREDOXIN 71 72 RXN02325 WV0047 5527 6393 THIOREDOXIN 73 74 RXN01 837 WV0320 7103 7879 PEPTIDYL-PROLYL CIS-TRANS ISOMERASE (EC 5.2.1.8) 76 RXN01926 W0284 1 741 PEPTID KETTE RELEASE FACTOR 3 77 78 RXN02002 WV0111l 141 518 PEPTID KETTE RELEASE FACTOR 3 79 80 RXN02736 WV0074 13600 14556 PUTATIVES OXPPCYCLE PROTEIN OPCA 81 82 RXS03217 SMALL COLD-SHOCK PROTEIN 83 84 F RXA01917 GR00549 3465 3665 SMALL COLD-SHOCK PROTEIN Proteins involved in stress responses Nucleic Acid Amino Acid Identification Code SEQ ID NO SEQ ID, NO 86 RXA02184 87 88 RXAOO810 89 90 RXA01 674 91 92 RXA02431 93 94 R.XA02446 96 RXA02861 97 98 RXAO981 99 100 RXN00786 101 102 RXS01027 103 104 RXS01 528 105 108 RXS501716 107 108 RXS01 835 109 110 RXS02497 '1111 112 RXS02972 Resistance and tolerance Nucleic Acid Amino Acid Identification Code SEQ ID, NO SEQ -IDNO 113 114 RXA02159 115 116 RXA02201 117 1118 RXA00599 119 120 .RXA00600 121 122 RXA02200 123 124 RXA02202 125 126 RXA02205 127 128 RXA00900 Contig. NT Star NT Stop Function GR00641 19628 19248 COLD SHOCK-LIKE PROTEIN CSPC GR00218 792 992 SMALL COLD-SHOCK PROTEIN GR00467 1878 2771 PROBABLE HYDROGEN PEROXIDE-INDUCIBLE GENES ACTIVATOR GR00708 2 1192 damage-inducible protein P GR00709 11640 11206 OSMOTICALLY INDUCIBLE PROTEIN C GRI0006 551 1633 probable metallothionein u03O8aa Mycobacterium leprae GR00276 3388 4017 GTP PYROPHOSPHOKINASE (EC 2.7.6.5) WV0321 1680 706 LYTB PROTEIN WV0143 5761 6768 DIADENOSINE 5',5"'-P1,P4-TETRAPHOSPHATE H-YDROLASE (EC 3.6.1.17) WV0050 17276 16749 DIADENOSINE 5',5-P,P4-TETRAPHOSPHATE HYDROLASE (C 3.6.1.17) WV0319 3259 2774 EXOPOLYPHOSP-ATASE (EC 3.6. 1.11) WV0143 10575 10045 GUANOSINE-3,5'-BIS(DIPHOSPHATE) 3-PYROPHOSPHOHYDROLASE (EC 3.1.7.2) WV0007 15809 16535 EXOPOLYPHOSPHATASE (EC 3.6. 1.11) WV0319 2763 2353 EXOPOLYPHOSPHATASE (EC 3.6.1.11) Conti.
GRO0640 GR00646 GROO 159 GROC 159 GR00646 GR00646 GROO846 GR00245 NT Stas NT Stop 6231 6743 5837 6199 1843 1457 2940 1843 4651 5760 6278 6916 9871 8993 4052 3201 Function ARGININE HYDROXIMATE RESISTANCE PROTEIN ARSENATE REDUCTASE ARSENICAL-RESISTANCE PROTEIN ACR3 ARSENICAL-RESISTANCE PROTEIN ACR3 ARSENICAL-RESISTANCE PROTEIN ACR3 ARSENICAL-RESISTANCE PROTEIN ACR3 BACITRACIN RESISTANCE PROTEIN (PUTATIVE UNDECAPRENOL KINASE) (EC, 2.7.1.66) BICYCLOMYCIN RESISTANCE PROTEIN Nucleic Acid SEQ ID, NO 129 131 133 135 137 139 141 143 145 147 149 151 153 155 157 159 161 163 165 167 169 171 173 175 177 179 181 183 185 187 189 191 193 195 197 199 201 203 205 207 209 211 213 215 217 219 221 Amino Acid SEQ ID0 NO 130 1132 134 138 140 142 144 146 148 150 152 154 156 158 160 162 164 166 168 170 172 174 176 178 180 182 184 186 188 190 192 194 196 198 200 202 204 206 208 210 212 214 216 218 220 222 Identificalion Code RXNO0901 F RXA00901 RXA00289 RXN01 984 F RXAO 1984 RXA00109 RXA001 09 RXA00996 RXN00829 F RXA00829 F RXA00834 RXA00995 RXN00803 F RXA00803 RXA0 1407 RXA01 408 RX N01922 F RXA0 1922 RXA02060 RXN0 1936 F RXA01 936 F RXA01937 RXNO1O1 0 F RXA01O010 RXN03142 F RXAO1 150 RXN02964 F RXAO2116 RXA00858 RXA02305 RXA00084 RXA00843 RXA01052 RXA01053 RXA01054 RXN03 123 IF RXA00993 RXA01051 RXN0 1873 F RXA01873 RXN00034 F RXA02273 RXN03075 F RXA02907 RXA00479 RXN03124 F RXA01I180 Table I (continued) Contig NT Start NT Stop W0140 8581 8168 GR00245 4357 3980 GR00046 3263 4438 WV0056 1515 1811 GR00574 282 4 GROO015 1176 565 GROO01 5 1176 565 GR00283 1763 1023 WV0160 7950 5611 GR00224 2 256 GR00225 463 2025 GR00283 1023 283 WV0009 53858 52629 GR00214 4560 5162 GROO410 3918 3028 GROO410 4384 4184 VV0020 2031 3182 GR00552 3 1109 GRO0626 1 339 WV0127 40116 41387 GR00555 9796 8975 GRCO555 10246 9821 WV0209 3776 4894 GR00288 774 4 WV0136 5754 4612 GR00323 3807 2917 WV0102 7931 6714 GR00636 911 6 GR00233 1680 2147 GR00663 2921 2070 GROO013 2367 1543 GR00228 3236 3580 GR00296 3398 3706 GR00296 3772 4191 GR00296 4229 4717 WV0106 808 1245 GR00282 6411 6 GR00296 3298 2690 W0248 2054 819 GR00535 855 1946 WV0020 16933 18381 GR0D655 8058 9002 WV0042 2491 3216 GR10044 1395 2120 GRO01I19 16290 14101 WV0108 4 963 GR00336 4 765 Function BICYCLOMYCIN RESISTANCE PROTEIN BICYCLOMYCIN RESISTANCE PROTEIN CHLORAMPHENICOL RESISTANCE PROTEIN CHLORAMPHENICOL RESISTANCE PROTEIN CHLORAMPHENICOL RESISTANCE PROTEIN COPPER RESISTANCE PROTEIN C PRECURSOR COPPER RESISTANCE PROTEIN C PRECURSOR DAUNORUBICIN RESISTANCE ATP-BINDING PROTEIN DRRA DAUNORUBICIN RESISTANCE PROTEIN DAUNORUBICIN RESISTANCE PROTEIN DAUNORUBICIN RESISTANCE PROTEIN DAUNORUBICIN RESISTANCE TRANSMEMBRANE PROTEIN METHYLENOMYCIN A RESISTANCE PROTEIN METHYLENOMYCIN A RESISTANCE PROTEIN METHYLENOMYCIN A RESISTANCE PROTEIN METHYLENOMYCIN A RESISTANCE PROTEIN METHYLENOMYCIN A RESISTANCE PROTEIN METHYLENOMYCIN A RESISTANCE PROTEIN MYCINAMICIN-RESISTANCE PROTEIN MYRA MACROLIDE-EFFLUX PROTEIN NICKEL RESISTANCE PROTEIN NICKEL RESISTANCE PROTEIN QUINOLONE RESISTANCE NORA PROTEIN QUINOLONE RESISTANCE NORA PROTEIN QUINOLONE RESISTANCE NORA PROTEIN QUINOLONE RESISTANCE NORA PROTEIN QUINOLONE RESISTANCE NORA PROTEIN QUINOLONE RESISTANCE NORA PROTEIN TELLURIUM RESISTANCE PROTEIN TERC DAUNOMYCIN C-14 HYDROXYLASE VIBRIOBACTIN UTILIZATION PROTEIN VIUB ARSENATE REDUCTASE MERCURIC REDUCTASE (EC 1.16.1.1) MERCURIC REDUCTASE (EC 1.16.1.1) MERCURIC REDUCTASE (EC 1.16.1.1) HEAVY METAL TOLERANCE PROTEIN PRECURSOR HEAVY METAL TOLERANCE PROTEIN PRECURSOR VANZ PROTEIN ,teicoplanin resistance protein Hypothetical Drug Resistance Protein Hypothetical Drug Resistance Protein MULTIDRUG RESISTANCE PROTEIN B Hypothetical Drug Resistance Protein Hypothetical Drug Transporter Hypothetical Drug Transporter Hypothetical Drug Transporter Hypothetical Drug Transporter Hypothetical Drug Transporter Table I (continued) Nucleic Acid Amino Acid Identification Code C ont NT Start NT Stop SEQ ID NO SEQID NO 223 224 RXA02586 GR00741 10296 10027 225 226 RXA02587 GR00741 12343 10253 227 228 RXN03042 wool18 2440 1835 229 230 F RXA02893 GR10035 1841 1236 231 232 RXA01616 GR00450 1654 203 233 234 RXA01666 GROO463 2307 3683 235 238 RXA00062 GROO009 13252 11855 237 238 RXA00215 GROO032 13834 15294 239 240 RXN03064 WV0038 4892 6223 241 242 F RXA00565 GROO151 4892 5884 243 244 F RXA02878 GR10016 1837 1481 245 246 RXA00648 GR00169 2713 1304 247 248 RXN01320 W0082 13146 11500 249 250 F RXAO1 314 GR00382 744 4 251 252 F RXA01320 GRO0383 1979 1200 253 254 RXN02926 W0082 11497 9866 255 256 F RXA01319 GR00383 1197 4 257 258 RXA01578 GR00439 1423 29 259 260 RXA02087 GR00629 7076 5730 261 262 RXA02088 GROO629 8294 7080 263 264 RXA00764 GR00204 3284 2169 265 266 RXN031125 VV0108 972 1142 267 268 RXN01553 W0135 25201 26520 269 270 RXN00535 W0219 5155 5871 271 272 RXN00453 VV0076 1173 3521 273 274 RXN00932 W0O171 13120 13593 275 276 RXN03022 VV0002 65 511 277 278 RXN03151 W0163 489 4 279 280 RXN02832 W0358 547 5 281 282 RXNOO165 WV0232 3275 1860 283 284 RXN01190 WV0169 8992 10338 285 286 RXNO1IO02 W0059 6128 4884 287 288 RXN00788 WV0321 3424 3648 289 290 RXN02119 W0102 11242 9602 291 292 RXN01605 W0137 7124 5610 293 294 RXN01 091 WV0326 567 4 295 296 RXS02979 W0149 2150 2383 297 298 RXS02987 W0234 527 294 299 300 RXS03095 W0057 4056 4424 Hypothetical Drug Transporter Hypothetical Drug Transporter Hypothetical Drug Transporter Hypothetical Drug Transporter MULTIDRUG EFFLUX PROTEIN QACB MULTIDRUG RESISTANCE PROTEIN MULTIDRUG RESISTANCE PROTEIN B MULTIORUG RESISTANCE PROTEIN B MULTIDRUG RESISTANCE PROTEIN 13 MULTIDRUG RESISTANCE PROTEIN B MULTIDRUG RESISTANCE PROTEIN B MULTIDRUG RESISTANCE PROTEIN B MULTIDRUG RESISTANCE PROTEIN B MULTIDRUG RESISTANCE PROTEIN B MULTIDRUG RESISTANCE PROTEIN B MULTIDRUG RESISTANCE PROTEIN B MULTIDRUG RESISTANCE PROTEIN B MULTIDRUG RESISTANCE PROTEIN B MULTIDRUG RESISTANCE PROTEIN B MULTIDRUG RESISTANCE PROTEIN B BMRU PROTEIN Bacillus subtilis bmrU, multidrug efflux transporter Hypothetical Drug Transporter Hypothetical Drug Permease Hypothetical Drug Resistance Protein Hypothetical Drug Transporter Hypothetical Drug Transporter MULTIDRUG RESISTANCE PROTEIN B MYCINAMICIN-RESISTANCE PROTEIN MYRA LYSOSTAPHIN IMMUNITY FACTOR MULTIDRUG RESISTANCE-LIKE ATP-BINDING PROTEIN MDL MULTIDRUG RESISTANCE-LIKE ATP-BINDING PROTEIN MDL QUINOLONE RESISTANCE NORA PROTEIN CHLORAMPHENICOL RESISTANCE PROTEIN A2O1A-RESISTANCE ATP-BINDING PROTEIN DAUNORUBICIN RESISTANCE TRANSMEMBRANE PROTEIN MAZG PROTEIN MERCURIC TRANSPORT PROTEIN PERIPLASMIC COMPONENT PRECURSOR MERCURIC TRANSPORT PROTEIN PERIPLASMIC COMPONENT PRECURSOR CADMIUM EFFLUX SYSTEM ACCESSORY PROTEIN HOMOLOG TABLE 2 Excluded Genes GenBankTu Gene Name Gene Function Reference Accession No.
A09073 pPg Phosphoenol pyruvate carboxylase Bachmann, B. et al. "DNA fragment coding for phosphoenolpyruvat corboxylase, recombinant DNA carrying said fragment, strains carrying the recombinant DNA and method for producing L-aminino acids using said Patent: EP 0358940-A 3 03/21/90 A45579, Threonine dehydratase Moeckel, B. et al. "Production of L-isoleucine by means of recombinant A4558 1, micro-organisms with deregulated threonine dehydratase," Patent: WO A45583, 9519442-A 5 07/20/95 A45585 A45587 AB003 132 murC; ftsQ; ftsZ Kobayashi, M. et al. "Cloning, sequencing, and characterization of the ftsZ gene from coryneform bacteria," Biuchem. Biophys. Res. Comm un., (1997) ABO 15023 murC; ftsQ Wachi, M. ct al. "A murC gene from Coryneform bacteria," Appi. MicrobioL 5 1(2):223-228 (1999) AB018530 dtsR Kimura, E. et al. "Molecular cloning of a novel gene, dtsR, which rescues the detergent sensitivity of a mutant derived from Brevibacterium Biosci. Biotechnol. Biochem., 60(10): 1565-1570 (1996) A8018531 dtsRlI; dtsR2 AB020624 muri D-glutamate racemase AB023377 tkt transketolase AB024708 gltB; girD Glutaniine 2-oxoglutarate aminotransferase and small subunits AB025424 acn aconitase AB0277 14 rep Replication protein AB027715S rep; aad Replication protein; aminoglycoside __________________adenyltransferase AF005242 argC N-acetylglutamate-S-semiaidehyde AF005635 ginA Glutamine synthetase AF030405 hisF cyclase AF030520 argG Argininosuccinate synthetase A F031 18I argF Ornithine AF036932 aroD I3-dehydroquinate IAF038548 pyc Pyruv'ate 0 0 0 0 00 0 0~~ 0 0 0 0 0 '0 Table 2 (continued) AF038651 dciAE; apt; rel Dipeptide-binding protein; adenine Wehmeier, L. et al. "The role of the Corynebacterium glutamicum rel gene in phosphoribosyliransferase, GTP (p)ppGpp metabolism," Microbiology, 144:1853-1862 (1998) _____________pyrophosphokinase AF04 1436 argR Arginine repressor AF045998 impA Inositol monophosphate phosphatase AF048764 argH Argininosuccinate lyase AF049897 argC; arg.); argB; N-acetyIg lutamylIphosphate reductase, argD; argF; argR; ornithine acetyltransferase; NargG; argH- acetylgiutamate kinase; acetylomnithine transminase; omithine carbamoyltransferase; arginine repressor; argininosuccinate synthase; _____________argininosuccinate lyase AF050 109 inhA Enoyl-acyl carrier protein reductase AF050 166 hisG ATP ph osphoribosylItran sfe rase AFOS 1846 hisA Phosphoribosylformnimino-5-amino- 1phosphoribosyl-4-imidazulecarboxamide i somerase AF052652 metA H-omoscrine 0-acetyltransferase Park, S. et al. "Isolation and analysis of metA, a methionine biosynthetic gene encoding homoserine acetyltransferase in Corynebacterium glutamicum," Mo!.
8(3):286-294 (1998) AF053071 aroB Dehydroquinate AF060558 hisH Glutamine amidotransferase AF086704 hisE Phosphoribosyl-ATPpyrophosphohydro lase AFI 114233 aroA 5-enolpyruvyishikiniate 3-phosphate A F 16184 panD L-aspartate-alpha-decarboxylase precursor Dusch, N. et al. "Expression of the Corynebacteriumn glutamicum panD gene encoding L-aspartate-alpha-decarboxy lase leads to pantothenate overproduction in Escherichia col," App!. Environ. Micrabiol., 65(4)1530- (1999) AF124518 aroD; aroE 3-dehydroquinase; shikimate AF124600 aroC; aroK; aroB; Chorismate synthase; shikimate kinase; 3pepQ dehydroquinate synthase; putative cytoplasmic AF145897 inbA AF145898 inhA 2 (continued) AJGO01436 ectP Transport of ectoine, glycine betaine, Peter, H. et al. "Corynebacterium glutamicum is equipped with four secondary proline carriers for compatible solutes: Identification, sequencing, and characterization of the proline/ectoine uptake system, ProP, and the ectoine/proline/glycine carrier, EctP," J Bacteriol., 1 80(22):6005-6012 (1998) AJ004934 dapD Tetrahydrodipicolinate succinylase Wehrmann, A. et al. "Different modes of diaminopimelate synthesis and their (incomplete') role in cell wall integrity: A study with Corynebacterium glutamicum," J 180(12):3159-3165 (1998) AJO07732 ppc; secG; amt; ocd; Phosphoenolpyruvate-carboxy lase; high soxA affinity ammonium uptake protein; putative omnithine-cyclodecarboxylase; sarcosine oxidase AJO103 19 fisY, glnB, gInD; srp; Involved in cell division; P111 protein; Jakoby, M. et al. "Nitrogen regulation in Corynebacterium glutamicum; amtP uridylyltransferase (uridylyl-removing Isolation of genes involved in biochemical characterization of corresponding enzniye); signal recognition particle; low proteins," FEMS Microbial., 1 73(2):303-3 10 (1999) ammonium uptake All132968 cat Chloramphenicol aceteyl transferase AJ224946 mqo L-malate: quinone oxidoreductase Molennar, D. et al. "Biochemical and genetic characterization of the me mbran e-assoc iated malate dehydrogenase (acceptor) from Corynebacterium Eur. J Biochem., 254(2):395-403 (1998) AJ238250 ndh NADH dehydrogenase AJ238703 porA Porin Lichtinger, T. et al. "Biochemical and biophysical characterization of the cell wall porin of Corynebacterium glutamicum: The channel is forned by a low mass polypeptide," Biochemistry, 37(43): 15024-15032 (1998) Dl 7429 Transposable element IS3 1831 Vertes et al."Isolation and characterization of IS3 183 1, a transposable element Corynebacterium glutamicum," Mo! Microbiol, I1 (4):739-746 (1994) D84 102 odhA 2-oxoglutarate dehydrogenase Usuda, Y. et al. "Molecular cloning of the Corynebacterium glutamicum (Brevibacterium lactofermentumn Al 12036) odhA gene encoding a novel type 2-oxoglutarate dehydrogenase," Microbiology, 142:3347-3354 (1996) E01358 hdh; hk Homoserine dehydrogenase; homoserine Katsumata, R. et al. "Production of L-thereonine and L-isoleucine," Patent: JP kinase 1987232392-A I 10/12/87 E01359 Upstream of the start codon of homoscrine Katsumata, R. et al. "Production of L-thereonine and L-isoleucine," Patent: JP kinase gene 1987232392-A 2 10/12/87 E01375 Tryptophan operon E01376 trpL; rrpE Leader peptide; anthranilate synthase Matsui, K. et al. "Tryptophan operon, peptide and protein coded thereby, utilization of tryptophan operon gene expression and production of tryptophan," Patent: JP 1987244382-A I 10/24/87 2 (continued) E01 377 Promoter and operator regions of Matsui, K. et al. "Tryptophan operon, peptide and protein coded thereby, tryptophan operon utilization of tryptophan operon gene expression and production of ryptophan," Patent: JP 1987244382-A 1 10/24/87 E03937 IBiotin-synthase Hatakeyama, K. et al. "DNA fragment containing gene capable of coding synthetase and its utilization," Patent: JP 1992278088-A I 10/02/92 E04040 Diamino pelargonic acid aminotransferase Kohama, K. ct al. "Gene coding diaminopelargonic acid aminotransferase and desthiobiotin synthetase and its utilization," Patent: JP 1992330284-A I I 1/ 18/92 E04041 Desthiobiotinsynthetase Kohama, K. et al. "Gene coding diaminopelargonic acid aminotransferase and desthiobiotin synthetase and its utilization," Patent: JP 1992330284-A 1 E04307 Flavum aspantase Kurusu, Y. et al. "Gene DNA coding aspa-rtase and utilization thereof," Patent: JP 1993030977-A 1 02/09/93 E04376 Isocitric acid lyase Kaisumata, R. et al. "Gene manifestation controlling DNA," Patent: JP 3 03/09/93 E04377 Isocitric acid lyase N-terminal fragment Katsumala, R. et al. "Gene manifestation controlling DNA," Patent: JP 1993056782-A 3 03/09/93 E04484 Prephenate dehydratase Sotouchi, N. et al. "Production of L-phenylalanine by fermentation," Patent: JP 2 03/30/93 108 Aspartokinase Fugono, N. et al. "Gene DNA coding Aspartokinase and its use," Patent: JP 1 07/27/93 E051 12 Dihydro-dipichorinate synthetase Hatakeyama, K. et al. "Gcne DNA coding dihydrodipicolinic acid synthetase its use," Patent: JP 1993 184371]-A 1 07/27/93 E05776 Diaminopimelic acid dehydrogenase Kobayashi, M. et al. "Gene DNA coding Diamiinopimelic acid dehydrogenase its use," Patent: JP 1993284970-A 1 11/02/93 E05779 Trhreonine synthase Kohama, K. et al. "Gene DNA coding threonine synthase and its use," Patent: 1993284972-A 1 11/02/93 E061 10 Prephenate dehydratase jKikuchi, T. ct al. 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"DNA fragment having promoter function in bacterium," Patent: JP 199503 1476-A 1 02/03/95 E08649 Aspartase Kohama, K. et al "DNA fragment having promoter function in coryneform Patent: J1P 1995031478-A 1 02/03/95 E08900 Dihydrodipicolinate reductase Madori, M. et al. "DNA fragment containing gene coding Dihydrodipicolinate reductase and utilization thereof," Patent: JP 1995075578-A 1 03/20/95 E08901 Diaminopimelic acid decarboxylase Madori, M. et al. "DNA fragment containing gene coding Diaminopimelic acid ____________decarboxylase and utilization thereof," Patent: JP 1995075579-A 1 03/20/95 E£12594 Serine hydroxymethyltransferase Hatakeyama, K. et al. "Production of L-trypophan," Patent: JP 1997028391 -A 1 02/04/97 E12760, transposase Moriya, M. et al. "Amplification of gene using artificial transposon," Patent: E12759, J P 199707029 1-A 03/18/97 El12758 E12764 Arginyl-tRNA synthetase; diaminopimelic Moriya, M. et al. "Amplification of gene using artificial transposon," Patent: acid decarboxylase JP 1997070291 I-A 03/18/97 E12767 Dihydrodipicolinic acid synthetase Moriya, M. et al. "Amplification of gene using artificial transposon," Patent: 199707029 I -A 03/18/97 E12770 aspartokinase Moriya, M. et al. "Amplification of gene using artificial transposon," Patent: 1997070291-A 03/18/97 E12773 Dihydrodipicolinic acid reductase Moriya, M. et al. "Amplification of gene using artificial transposon," Patent: I JP 199707029 1-A 03/18/97 Table 2 (continued) E13655 Glucose-6-phosphate dehydrogenase Hatakeyama, K. et al. "Glucose-6-phosphate dehydrogenase and DNA capable of coding the same," Patent: JP 199722466 1I-A 1 09/02/97 LO 1508 IlvA Threonine dehydratase Moeckel, B. et al. "Functional and structural analysis of the threonine dehydratase of Corynebacterium glutamicum," .J Bacleriol., 174:8065-8072 L07603 EC 4.2.1.15 3-deoxy-D-arabinoheptulosonate-7- Chen, C. et al. 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Left.. 119(1-2): 137-145 (1994) L27 123 aceB Malate synthase Lee, H-S. et "Molecular characterization of aceB, a gene encoding malate synthase in Corynebacterium glutamicum," J. Microbial Biotechnol., (1994) L27 126 Pyruvate kinase Jetten, M. S. et al. "Structural and functional analysis of pyr-uvate kinase from Corynebacterium glutamicum," Appi. Environ. Microbial., 60(7):2501-2507 L28760 accA Isocitrate L35906 dtxr Diphtheria toxin repressor Oguiza, i.A. et al. "Molecular cloning, DNA sequence analysis, and characterization of the Corynebacterium diphtheriae dtxR from Brevibacterium lactofermentum," J. Bacteriol, 1 77(2):465-467 (1995) *M13774 Prephenate dehydratase Follettie, M.T. et al. "Molecular cloning and nucleotide sequence of the glutamicum pheA gene," J Bacterial.. 167:695-702 (1986) *M16175 5S rRNA Park, Y-H. et al. 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Gen. Genet., 212(1):112-119 (1988) X 14234 EC 4.1.1.31 Phosphoenolpyruvate carboxylase Eikmanns, 131. et al. "The Phosphoenolpyruvate carboxylase gene of Corynebacterium glutamicum: Molecular cloning, nucleotide sequence, and expression," MI. Gen. Genet., 218(2):330-339 (1989); Lepiniec, L. et al.
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Biolechnol., 42(4):575-580 (1994) X75504 aceA; thiX Partial Isocitrate lyase; Reinscheid, D.J. et al. "Characterization of the isocitrate lyase gene from Corynebacterium glutaniicum and biochemical analysis of the enzyme," J Bach'erioL, 176(1 2):3474-3483 (1994) X76875 ATPase beta-subunit Ludwig, W. et al. "Phylogenetic relationships of bacteria based on comparative sequence analysis of elongation factor Tu and ATP-synthase beta-subunit Antonie Van Leeuwvenhoek, 64:285-305 (1993) X77034 tuf Elongation factor Tu Ludwig, W. et al. "Phylogenetic relationships of bacteria based on comparat *ive sequence analysis of elongation factor Tu and ATP-synthase beta-subunit A nfonie Van Leeuwenhoek, 64:285-305 (1993) X77384 recA Billman-Jacobe, H. "Nucleotide sequence of a recA gene from _______________Corynebacteriumn glutamicum," DNA Seq., 4(6):403-404 (1994) X78491 aceB Malate synthase Reinscheid, D.J. et al. "Malate synthase from Corynebacterium glutamicumn pta-ack operon encoding phosphotransaccty lase: sequence analysis," Microbiology, 140:3099-3108 (1994) X80629 16S rDNA 16S ribosomal RNA Rainey, F.A. et al. "Phylogenetic analysis of the genera Rhodococcus and Norcardia and evidence for the evolutionary origin of the genus Norcardia from within the radiation of Rhodococcus species," Microbial, 141:523-528 X81 191 gluA; gluB; gluC; Glutamate uptake system Kronemeyer, W. et al. "Structure of the gluABCD cluster encoding the gluD glutamate uptake system of Corynebacterium glutamicum," J. Bacterial., 177(5):1 152-1 158 (1995) X81379 dapE Succinyld iam inopime late desuccinylase Wehrniann, A. et al. "Analysis of different DNA fragments of Coryriebacteriumn glutamicumn complementing dapE of Escherichia coli," 40:3349-56 (1994) 2 (continued) X82061 16S rDNA 16S ribosomal RNA Ruimy, R. et aL "Phylogeny of the genus Corynebacteriurn deduced from analyses of small-subunit ribosomal DNA sequences," Int. J Sys. Bacteriol., (1995) X82928 asd; lysC Aspartate-semialdehyde dehydrogenase; Serebrijski, 1. et al. "Multicopy suppression by asd gene and osmotic stressdependent complementation by heterologous proA in proA mutants," J Bactcriol., 1'77(24):7255-7260 (1995) X82929 proA Gamma-glutamyl phosphate reductase Serebrijski, 1. et al. "Multicopy suppression by asd gene and osmotic stressdependent complementation by heterologous proA in proA mutants," J 1 77(24):7255-7260 (1995) X84257 16S rDNA 16S ribosomal RNA Pascual, C. et al. "Phylogenetic analysis of the genus Corynebacterium based on 16S rRNA gene sequences," In. J Syst. Dacieriol, 45(4):724-728 (1995) X85965 aroP; dapE Aromatic amino acid permease; Wehrmann et al. "Functional analysis of sequences adjacent to dapE of C.
glutamicum proline reveals the presence of aroP, which encodes the aromatic amino acid transporter," J Bacteriol., 177(20);5991-5993 (1995) X86 157 argB; argC; argD; Acetylglutamate kinase; N-acetyl-gamma- Sakanyan, V. et al. "Genes and enzymes of the aceryl cycle of arginine argF; argi glutamnyl-phosphate reductase; biosynthesis in Corynebacterium glutamicum: enzyme evolution in the early acetylomithine aminotransferase; ornithine steps of the arginine pathway," Microbiology, 142:99-108 (1996) carbanioyltransferase; glutamate N- X89084 pta; ackA Phosphate acetyltransferase; acetate kinase Reinscheid, D.J. et al. "Cloning, sequence analysis, expression and inactivation of the Corynebacterium glutamicum pta-ack operon encoding phosphotransacetylase and acetate kinase," Microbiology, 145:503-5 13 (1999) X89850 attB Attachment site Le Marrec, C. et al. "Genetic characterization of site-specific integration functions of phi AAU2 infecting "Arthrobacter aureus C70," J Bacieriol., 178(7): 1996-2004 (1996) X90356 Promoter fragment Fl Patek, M. et al. "Promoters from Corynebacterium glutamicum: cloning, molecular analysis and search for a consensus motif," Microbiology, 142:1297-1309 (1996) X90357 Promoter fragment F2 Patek, M. et al. "Promoters from Corynebacterium glutanticum: cloning, molecular analysis and search for a consensus motif," Microbiology, 142:1297-1309 (1996) X90358 Promoter fragment FI10 Patek, M. et al. "Promoters from Corynebacterium glutamicurn: cloning, molecular analysis and search for a consensus motif," Microbiology, (1996) X90359 Promoter fragment F 13 Patek, M. et al. "Promoters from Corynebacterium glutamicum: cloning, molecular analysis and search for a consensus motif," Microbiology (1996) 2 (continued) X90360 Promoter fragment P2 Patek, M. et al. "Promoters from Corynebacterium glutaniicum: cloning, molecular analysis and search for a consensus motif," Microbiology 142:1297-1309 (1996) X90361 Promoter fragment F34 Patek, M. et al. "Promoters from Corynebacterium glutamicum: cloning, molecular analysis and search for a consensus motif," Microbiology, 142:1297-1309 (1996) X90362 Promoter fragment F37 Patek, M. et al. "Promoters from C. glulainicum: cloning, molecular analysis search for a consensus motif," Microbiology, 142:1297-1309 (1996) X90363 Promoter fragment F45 Patek, M. et al. "Promoters from Corynebacterium glutamicum: cloning, molecular analysis and search for a consensus motif," Microbiology, (1996) X90364 Promoter fragment F64 Patek, M. et al. "Promoters from Corynebacterium glutamicum: cloning, molecular analysis and search for a consensus motif," Microbiology, (1996) X90365 Promoter fragment F7S Patek, M. et al. "Promoters from Corynebacterium glutarnicum: cloning, molecular analysis and search for a consensus motif," Microbiology, (1996) X90366 Promoter fragment PP 101 Patek, M. et al. "Promoters from Corynebacterium glutamicum: cloning, molecular analysis and search for a consensus motif," Microbiology 142:1297-1309 (1996) X90367 Promoter fragment PF104 Patek, M. et al. "Promoters from Corynebacterium glutamicum: cloning, molecular analysis and search for a consensus motif," Microbiology (1996) X90368 Promoter fragment PF109 Patek, M. et al. "Promoters from Corynebacterium glutamicum: cloning, molecular analysis and search for a consensus motif," Microbiology (1996) X93513 amt Ammonium transport system Siewe, R.M. et al. "Functional and genetic characterization of the (methyl) ammonium uptake carrier of Corynebacterium glutamicum," J Biol. Chem., 271(10):5398-5403 (1996) X93514 betP Glycine betaine transport system Peter, Hi. et al. "Isolation, characterization, and expression of the Corynebacterium glutamicum betP gene, encoding the transport system for the compatible solute glycime betaine," J BacterioL, 178(1 7):5229-5234 (1996) X95649 orf4 Patek, M. et al. "Identification and transcriptional analysis of the dapB-ORF2dapA-ORF4 operon of Corynebacterium glutamicum, encoding two enzymes involved in L-lysine synthesis," Biotuchnol. Let., 19:1113-1117 (1997) X96471 IysE; IysG Lysine exporter protein; Lysine export Vrljic, M. et al, "A new type of transporter with a new type of cellular regulator protein function: L-lysine export from Corynebacterium glutamicum," Mod.
22(5):815-826 (1996) Table 2 (continued) X96580 panB; panC; xylB 3-methyl-2-oxobutanoate Sahm, H. et al. "D-pantothenate synthesis in Corynebacterium glutamicumn and hydroxymethyltransferase; panroate-beta- use of panBC and genes encoding L-valine synthesis for D-pantothenate0 alanine ligase; xylulokinase overproduction," Appi. Environ. Microbiol., 65(5):1973-1979 (1999) X96962 Insertion sequence IS 1207 and transposase X99289 Elongation factor P Ramos, A. et al. "Cloning, sequencing and expression of the gene encoding elongation factor P in the amino-acid producer Brevibacterium lactofermentum (Corynebactcrium glutamicum ATCC 13869)," Gene, 198:217-222 (1997) Y00140 thrB Homoserine kinase Mateos, L.M. et al. "Nucleotide sequence of the homoserine kinase (thrB) gene of the Brevibacterium lactofermentum," Nucleic Acids Res., 15(9):3922 (1987) Y00151 ddh Meso-d iam inopime late D-dehydrogenase Ishino, S. et al. "Nucleotide sequence of the meso-diam inopime late D- (EC 1.4.1 .16) dehydrogenase gene from Corynebacterium glutamicuni," Nucleic Acids Res., (1987) Y00476 thrA Homoserine dehydrogenase Mateos, L.M. et al. "Nucleotide sequence of the homoserine dehydrogenase (thrA) gene of the Brevibacterium lactofermentum," Nucleic Acids Res., 15(24):10598 (1987) Y00546 horn; thrB Homoserine dehydrogenase; homoserine Peoples, O.P. et al. "Nucleotide sequence and fine structural analysis of the kinase Corynebacterium glutamicum hom-thrB operon," Mot. Microbial., 2(t):63-72 t~ (1988) Y08964 murC; fisQ/divD; ftsZ U PD-N-acetylmuramate-alanine ligase; Honrubia, M.P. et al. "Idencification, characterization, and chromosomal division initiation protein or cell division organization of the ftsZ gene from Brevibacterium lactofermentum," Mo. Gen.
protein; cell division protein Gene., 259(1):97-104 (1998) Y09 163 putP High affinity proline transport system Peter, H. et al. "Isolation of the putP gene of Corynebacterium glutamicumproline and characterization of a low-affinity uptake system for solutes," Arch. Microbial., 168(2): 143-151 (1997) Y09548 pyc Pyruvate carboxylase Pete rs- Wend isch, P.G. et al. "Pyruvate carboxylase from Corynebacterium glutamicum: characterization, expression and inactivation of the pyc gene," 144:915-927 (1998) Y09578 leuB 3-isopropylmalate dehydrogenase Patek, M. et at. "Analysis of the leuB gene from Corynebacterium AppI. Microbial. Riatechnol., 50(1):42-47 (1998) Y 12472 Attachment site bacteriophage Phi- 16 Moreau, S. et al. "Site-specific integration of corynephage Phi- 16: The construction of an integration vector," Microbial., 145:539-548 (1999) Y12537 proP Prolinelcctoinc uptake system protein Peter, H1. et al. "Corynebacterium glutamicum is equipped with four secondary carriers for compatible solutes: Identification, sequencing, and characterization of the prolinelectoine uptake system, ProP, and the ectoine/proline/glycine betaine carrier, EctP," J Bacterial., 1 80(22):6005-60 12 (1998) Table 2 (continued) Y 13221 gInA Glutamine synthetase I Jakoby, M. et al. "Isolation of Corynebacterium glutamicum gInA gene glutamine synthetase I FEMS Microbial Lett., 154(1 1-88 (1997) Y 16642 lpd Dihydrol ipoamide Y 18059 Attachment site Corynephage 304L Moreau, S. et al. "Analysis of the integration functions of φ304L: An integrase module among corynephages," Virology, 255(1):150-159 (1999) Z21501 argS; lysA Arginyl-tRNA synthetase; diaminopimelate Oguiza, J.A. et al. "A gene encoding arginyl-tRNA synthetase is located in the decarboxylase (partial) upstream region of the lysA gene in Brevibacterium lactofermentum: Regulation of argS-lysA cluster expression by arginine," J 175(22):7356-7362 (1993) Z21502 dapA; dapB Dihydrodipicolinate synthase; Pisabarro, A. et al. "A cluster of three genes (dapA, orf2, and dapB) of dlihydrod ipicolinate reductase Brevibacterium lactofermentum encodes dihydrodlipicolinate reducrase, and a third polypeptide of unknown function,' J Bacteriol., I175(9):2743-2749 Z29563 th rC Threonine synthase Malumbres, M. et al. "Analysis and expression of the thrC gene of the encoded synthase," AppI. Environ. Microbial, 60(7)2209-2219 (1994) Z46753 16S rDNA Gene for 16S ribosomal RNA Z49822 sigA SigA sigma factor Oguiza, I.A. et al "Multiple sigma factor genes in Brevibacterium lactofennentum: Characterization of sigA and sigB," J Bacierial., 1 78(2):550- 553 (1996) Z49823 galE; dtxR Catalytic activity UDP-galactosc 4- Oguiza, J.A. et al "The galE gene encoding the UDP-galactose 4-epimerase of epimerase; diphtheria toxin regulatory Brevibacterium lactofermentum is coupled transcriptionally to the dmdR gene," Gene, 177:103-107 (1996) Z49824 orf 1; sigB SigB sigma factor Oguiza, J.A. et al "Multiple sigma factor genes in Brevibacterium lactofermentum: Characterization of sigA and sigB," J. Bacterial., 178(2):550.
(1996) Z66534 Transposase Correia, A. et al. "Cloning and characterization of an IS-like element present in the genome of Brevibacterium lactofermentumn ATCC 13869," Gene, A -sequence for this gene was published in the indicated reference. However, the sequence obtained by the inventors of the present application is significantly longer than the published version. It is believed that the published version relied on an incorrect start codon, and thus represents only a fragment of the actual coding region.
WO 01/00804 WO 0100804PCT/IBOO/00922 -74- TABLE 3: Corynebactenum and Brevibacteriuin Strains Which May be Used in the Practice of the Invention Brevibacterium ammoniagenes 21054 Brevibacterium ammoniagenes 19351 Brcvibacterium ammoniagenes 19352 Brevibacterium arnmonagenes 193532___ Brevibacterium ammoniagenes 19354 Brevibacterium ainmoniagenes 19355 Brevibactcrium animoniagenes 19356 Brevibacterium ammoniagenes 10355 Brevibacterium ammoniagenes 21077 Brevibacterium ammoniagenes 21553 Brevibacterium ammoniagenes 21580 Brevibacterium ammoniagenes 3150 Brevibacterium butanicum 21196 Brevibacterium divaricatum 21792 P928 Brevibacterium flavum 21474 Brevibacterium flavum 21129 Brevibacterium flavum 21518 Brevibacterium flavum BI 1474 Brevibacterium flavum BI 11472 Brevibacterium flavum 21127 Brevibacterium tiavum 21128 Brevibacterium flavum 21427 Brevibacterium tiavum 21475 Brevibacterium tiavum 21517 Brevibacterium flavum 21528 Brevibacterium flavum 21529 Brevibacterium flavum BI 11477 Brevibacterium flavum BI 11478 Brevibacterium flavum 21127 Brevibacterium flavum BI 11474 Brevibacterium healii 15527 Brevibacterium ketoglutamicum 21004 Brevibacterium ketoglutamicum 21089 Brevibacterium ketosoreductum 21914 Brevibacterium lactofermentum Brevibacterium lactofermentum 74 Brevibacterium lactofermentum 77 Brevibacterium lactofermentum 21798 Brevibacterium lactofermentum 21799 Brevibacterium lactofermentum 21800 Brevibacterium lactofermentum 21801 Brevibacterium lactofermentum BI 11470 Brevibactcrium Ilactofcrrnentum BI 1471 WO 01/00804 WO 0100801PCT/1B00100922 75 Brevibacrerium lactofermentrm 21086 Brevibacterium lactofermnentumn 21420 Brevibacterium lactoferinentumn 2M86 Brevibacterium lactofermentumn 31269 Brevibacterium linens 9174 Brevibacterium linens 19391 Brevibacterium linens 8377 Brevibacterium paraffinolyticum ____11160 Brevibacterium Spec. 717.73 Brevibacterium Spec. 717.73 Brevibacterium Spec. 14604 Brevibacterium Spec. 21860 Brevibacterium Spec. 21864 Brevibacterium Spec. 21865 Brevibacterium Spec. 21866 Brevibacterium Spec. 19240 Corynebacterium acetoacidophilumn 21476 Corynebacterium acetoacidophilumn 13870 Corynebacterium acetoglutamicum BI 11473 Corynebacterium acctoglutamicum BI 11475 Corynebacterium acetoglutamnicum 15806 Corynebacterium acetoglutamnicumn 21491 Corynebacterium acetoglutamnicumn 31270 Corynebacterium acetophilum B3671 Corynebactcrium ammoniagenes 6872 2399 Corynebacterium ammoniagenes 15511 Corynebacterium fujiokense 21496 Corynebacterium glutarnicumn 14067 Corynebacterium glutamnicum 39137 Corynebacterium glutamnicumn 21254 Corynebacterium glutamnicumn 21255 Corynebacterium glutamnicumn 31830 Corynebacterium glutarnicumn 13032 Corynebacterium glutamnicumn 14305 Corynebacterium glutamicumn 15455 Corynebacterium glutamnicumn 13058 Corynebacteriwn glutrmicumn 13059 Corynebacterium glutamnicumn 13060 Corynebacterium glutamnicumn 21492 Corynebacterium glutamnicumn 21513 Corynebacterium glutamnicumn 21526 Corynebacterium glutamnicumn 21543 Corynebacterium glutamnicumn 13287 Corynebacterium glutamnicumn 2 1851 Corynebacterium glutrmicumn 21253 Corynebactenium glutamnicum 21514 Corynebactenium glutamnicumn 21516 Corynebacterium glutamnicumn 21299 WO 01/00804 WO 0100804PCTIIBOO/00922 76 A~5~ ~ERM NRRV CE~J C SI C orynebacterium glutamicum 21300 Corynebacterium glutamicum 39684 Corynebacterium glutamnicum 21488 Corynebacterium glutaniicum 21649 Corynebacterium glutamicum 21650 Corynebacterium glutamicum 19223 Corynebacterium glutamicum 13869 Corynebacterium glutamicum 21157 Corynebacterium glutamicum 21158 Corynebacterium glutaniicum 21159 Corynebacterium glutamicum 21355 Corynebacterium glutamicum 31808 Corynebacterium glutainicum 21674 Corynebacterium glutamicum 21562 Corynebacterium glutamicum 21563 Corynebacterium glutamicum 21564 Corynebacterium glutamicum 21565 Corynebacterium glutamicum 21566 Corynebacterium glutamicum 21567 Corynebacterium glutamicum 21568 Corynebacterium glutamicum 21569 Corynebacterium glutamicum 21570 Corynebacterium glutamicum 21571 Corynebacterium glutamicum 21572 Coryncbactcrium glutamicum 21573 Corynebacterium glutamicum 21579 Corynebacterium glutamicum 19049 Corynebacterium glutainicum 19050 Corynebacterium glutamicum 19051 Corynebacterium glutamicum 19052 Corynebacterium glutamicum 19053 Corynebacterium glutaxnicum 19054 Corynebacterium glutaxnicum 19055 Corynebacterium glutamicum 19056 Corynebacterium glutaniicum 19057 Corynebacterium glutamicum 19058 Corynebacterium glutaniicum 19059 Corynebacterium glutaniicum 19060 Corynebacterium glutamicum 19185 Corynebacterium glutamicum 13286 Corynebacterium glutainicum 21515 Corynebacterium glutamicum 21527 Corynebacterium glutaniicum 21544 Corynebacterium glutainicum 21492 Corynebacterium glutamicum Corynebacterium glutamicum 182 Corynebacterium glutamicum lCorynebacterium Iglutaniicum B12417 WO 01/00804 WO 0100804PCT/11B00/00922 77 Corynebacterium glutamicum ___B12418 Corynebacterium glutamicum _BI 11476 Corynebacterium glutamicumn 21608 Corynebacterium lilium P973 Corynebacterium nitrilophilus 21419 11594 Corynebacterium spec. P4445 Corynebacterium spec. _____P4446 Corynebacterium spec. 31088 Corynebacteriumn spec. 31089 Corynebacterium spec. 31090 Corynebacterium spec. 31090 Corynebacterium spec. 31090 Corynebacterium spec. 15954 20145 Corynebacteriumn spec. 21857 Corynebacterium spec. 21862 Corynebacterium Ispec. 21863 ATCC: American Type Culture Collection, Rockville, MD, USA FERM: Fermentation Research Institute, Chiba, Japan NRRL: ARS Culture Collection, Northern Regional Research Laboratory, Peoria, IL, USA CECT Coleccion Espanola de Cultivos Tipo, Valencia, Spain NCIMB: National Collection of Industrial and Marine Bacteria Ltd., Aberdeen, UK CBS: Centraalbureau voor Schimmelcultures, Baam, NL NCTC: National Collection of Type Cultures, London, UK DSMZ: Deutsche Sanimlung von Mikroorganismen und Zeilkulturen, Braunschweig, Germany For reference see Sugawara, H. et al. (1993) World directory of collections of cultures of microorganisms: Bacteria, fungi and yeasts 4 h~ edi), World federation for culture collections world data center on microorganisms, Saimata, Japen.
TABLE 4: ALIGNMENT RESULTS Lenath Accession Name of Genbank Hit IDO lengthl Genbank HIt
(NT)
Source of Genbank Hit homology Date of (GAP) Deot 39.080 5-Jun-99 rxa00062 1521 GB-HTG2:AC007366 185001 AC007366 Homo sapiens dlone NH0501G22, SEQUENCING IN PROGRESS 3 unordered pieces.
rxa00084 948 GB -PR3:HSU80741 912 U80741 Homo sapiens CAGH44 mRNA, partial cds.
GBPLI:BNDNATRNA 1732 X89901 B.nigra DNA for tRNA like gene.
GBPR3:HSU80741 912 U80741 Homo sapiens CAGH44 mRNA. partial eds.
=0aO1109 735 GB-GSS9:AQ163721 388 AQ163721 HS_72245_AlF07_MF CIT Approved Human Genomic Sperm Library 0 Homo sapiens genomic clone Plate=2245 Col=1 3 Row--K, genornic survey sequence.
GBHTG4:AC007054 171979 AC007054 Drosophila melanogaster chromosome 2 clone BACR45018 (D527) RPCI-98 45.0.18 map 41 E-41 E strain y: cn bw sp. -SEQUENCING IN PROGRESS- 13 unordered pieces.
GB-HTG4:AC007054 171979 AC007054 Drosophila melanogaster chromosome 2 clone BACR4501 8 (0527) RPCI-98 45.0.18 map 41lE-41lE strain y; cn bw sp, SEQUENCING IN PROGRESS-, 13 unordered pieces.
=00O215 1449 GB-BA1:SC9C7 31360 AL035161 Streptomyces coelicolor cosmid 9C7.
GB-BA1 :SCE94 38532 AL049628 Streptomyces coelicolor cosmid E94.
GBBA2.AF1 10185 20302 AF110185 Burkholderia pseudomalle strain 1026b DbhB (dbhB), general secretory pathway protein D (gspD). general secretory pathway protein E (gspE). general secretory pathway protein F (gspF), GspC (gspC), general secretory pathway protein G (gspG), general secretory pathway protein H (gspH), general secretory pathway protein I (gspl), general secretory pathway protein J (gspJ), general secretory pathway protein K (gspK), general secretory pathway protein L (gspL). general secretory pathway protein M (gspM), and general secretory pathway protein N (gspN) genes, complete cds: and unknown genes.
rxa00289 1299 GB-EST6:N80167 384 N80167 za65g02.sl Soares fetal liver spleen 1 NFLS Homo sapiens cDNA clone IMAGE:297458 mRNA sequence.
GBSTS:G370B4 384 G37084 SHGC-56832 Human Homo sapiens STS genomic, sequence tagged site.
GB..5TS:G37084 384 G37084 SHGC-56832 Human Homo sapiens STS genomic, sequence tagged site.
rxaOO404 2439 GBBA1:MTCY22D7 31859 Z83866 Mycobactedum tuberculosis H37Rv complete genome; segment 133/162.
Homo sapiens Homo sapiens Brassica nigra Homo sapiens Homo sapiens 39,264 36,725 38,957 45,066 Drosophila melanogaster 36,589 Drosophila melanogasler 36,589 18-DEC.1997 6-Feb-97 18.0DEC-1997 16-OCT-1998 13-OCT.1999 13-OCT.1999 12-Jan-99 12-Apr-99 2-Aug-99 Streptomyces coelicolor Streptomyces coelicolor Burkholderia pseudomallei Homo sapiens Homo sapiens Homo sapiens Mycobacterium tuberculosis Escherichia coli Escherichia coli Streptomyces coelicolor A3(2) 44,444 36,313 44,159 40,420 29-MAR-1996 40.420 30-MAR-1998 40,420 30-MAR.1998 GB-BAI:ECU82598 GB-BA2:AE0O0i65 rxa00479 2313 GB-BA1:SCF43A 136742 U82598 12003 AE000165 35437 AL096837 Esoherichia coi genomic sequence of minutes 9 to 12.
Escherichia coli K-12 MG1655 section 55 of 400 of the complete genome.
Streptomyces coelicolor cosmid F43A.
60,271 54,256 54,256 35,245 17-Jun-98 -3 15-Jan-97 12-Nov-98 3 13-Jul-99 26-Jul-99 GB-GSS2:CNS015U4 1036 AL105910 Drosophila melanogaster genome survey sequence SF6 end of BAG BACN14GO8 Drosophila melanogaster 37,573 of DrosBAC library from Drosophila melanogaster (fruit fly). genomic survey sequence.
GBPR3:HSA494016 rxaG0497 420 GBBA1:MTCY78 GB BA2:AF079544 GBBA1 :MTGROEOP 50502 33818 817 2987 ALl 17328 Z77 165 AF079544 X60350 Table 4 (continued) Human DNA sequence from clone 494016 on chromosome 22, complete sequence.
Mycobacterium tuberculosis H37Rv complete genome; segment 145/162.
Mycobacterium aviumn GroESL operon. partial sequence.
Mituberculosis groE gene for KCS and 10-kDa products.
Homo sapiens Mycobacteriumn tuberculosis Mycobacteriumn avlum Mycobacteriumn tuberculosis 36.475 40,250 64.439 62,857 23-Nov-99 17-Jun-98 16-Aug-98 23-Apr.92 rxa00575 rxa00599 510 GB_GSS1O:A0199703 439 A0 199703 GB-PR2:AC002127 144165 AC002127 GBSTS:G51234 439 G51234 rxca00600 1221 GB-BA1:MTCY441 35187 Z80225 GB-BAI:MSGY223 42061 AD000019 GBBA1:BSUB0014 213420 Z99117 1603 GB-BA2:AF069070 2776 AF069070 GBBA1:OVCAT 1845 X82176 GB_BA1:5C2G5 38404 AL035478 rxa00648 1533 GBHTGi:HS74016 169401 AL110119 GB-HTG1:HS74016 169401 AL110119 GB-HTGi:HS74016 169401 AL110119 rxa00764 1239 GB-EST36:A1898007 609 A1898007 GBBA2:PAU93274 8008 U93274 GB-BA2:PAU93274 8008 U93274 nca00803 1353 GB_1N2:CELH34CO3 27748 AF100662 GB-HTG2:AC007905 100722 AC007905 GB-HTG2:AC007905 100722 AC007905 RPCI1 I 46013.TJ RPCI-1 1 Homo sapiens genomic clone RPCI-1 1.46013, genomic survey sequence.
Human BAC clone RG305H12 from 7q21, complete sequence.
SHGC-80708 Human Homo sapiens STS genomic, sequence tagged site.
Mycobacteriumn tuberculosis H37Rv complete genome; segment 118/162.
Mycobacteriumn tuberculosis sequence from clone y 22 3.
Bacillus subtilis complete genome (section 14 of 21): from 2599451 to 2812870.
Endosymblont of Onchocerca volvulus calalase gene, complete cds.
Onchocerca volvulus endobacterial mRNA for catalase.
Streptomyces coelicolor cosmid 2G5.
Homo sapiens chromosome 21 clone RPCIP70401674 map 21q21, SEQUENCING IN PROGRESS in unordered pieces.
Homo sapiens chromosome 21 clone RPCIP70401674 map 21q21, SEQUENCING IN PROGRESS in unordered pieces.
Homo sapiens chromosome 21 clone RPCIP70401 674 map 21q21, SEQUENCING IN PROGRESS in unordered pieces.
EST267450 tomato ovary, TAMU Lycopersicon esculentumn cDNA clone cLED31 K22. mRNA sequence.
Pseudomnonas aeruginosa YafE (yafE), LeuB (leuB), Asd (asd), FimV (fimV), and HisT (hisT) genes, complete cds; TrpF (trpF) gene, partial cds; and unknown Pseudomonas aeruginosa YafE (yafE), LeuB (leuB), Asd (asd), FimV (f'imV), and HisT (hisT) genes, complete cds; TrpF (trpF) gene, partial cds; and unknown Caenorhabditis elegans cosmid H34C03.
Homo sapiens chromosome 16q24.3 clone PAC 754F23, SEQUENCING IN PROGRESS 33 unordered pieces.
Homo sapiens chromosome 16q24.3 clone PAC 754F23, SEQUENCING IN PROGRESS 33 unordered pieces.
Homo sapiens Homo sapiens Homo sapiens Mycobacterium tuberculosis Mycobacteriumn tuberculosis Bacillus sublilis endosymbionl of Onchocerca volvulus endosyrnbiont of Onchocerca volvulus Streptomyces coelicolor H-omo sapiens Homo sapiens Homo sapiens Lycopersicon esculentumn Pseudomonas aeruginosa Pseudomonas aeruginosa Caenorhabditis elegans Homo sapiens Homo sapiens 42,657 37,052 42,657 56.183 37,217 36,553 55,396 55,396 39,530 36,327 36,327 35,119 34.323 35,895 41,417 34 .152 37,472 37,472 20-Apr.99 27-MAY-1997 25-Jun-99 18-Jun-98 10-DEC-i1996 26-Nov.97 25-Nov-98 26-Nov-98' 11-Jun-99 27-Aug-99 27-Aug-99 27-Aug-99 27-Jul-99 23-Jun-98 23-Jun-98 28-OCT-i1998 24-Jun-99 24-Jun-99 rxaOO8lO 324 GB-BA1:MTY15C1O 33050 Z95436 GB BA1 :MLCB2548 GB BA1 :ECOUW76 rxa00829 2463 GBBA1:SC5C7 GB8BA1 :SC5F2A 38916 225419 41906 40105 AL023093 U00039 AL031515 AL049587 Table 4 (continued) Mycobacterium tuberculosis H37Rv complete genome; segment 154/162 Mycobacterium teprae cosmid 82548.
E. ccli chromosomal region from 76.0 to 81.5 minutes.
Streptomyces coelicotor cosmid 5C7.
Streptomyces coelicolor cosmid 5F2A.
Streptomyces peucetius daunorubicin resistance protein (drrC) gene, complete Mycobacterium tubercutosis H37Rv complete genome, segment 113/162.
Mycobacterium tuberculosis Mycobacteriumn teprae Esoherichia coli Streptomyces coelicolor Streptomyces coelicolor 34,615 34,615 52,997 65.269 37,490 117-Jun-98 27-Aug-99 7-Nov-96 7-Sep-98 24-MAY-1999 GBBA1:STMDRRC 3374 L76359 rxaO43 468 GBBAi:MTCY9C4 15916 Z77250 Streptomyces peucetius 55,279 Mycoboactefurn 40,000 tuberculosis Mycobacteriumn 37,773 tuberculosis 24-DEC-i1996 17-Jun-98 GB-BA1:MTCY9C4 15916 Z77250 Mycobacterium tuberculosis H37Rv complete genome; segment 113/162.
17-Jun-98 rxa00858 568 GBBAI:SCCS4 30753 GB-EST18:N96610 547 GB-EST18:T45493 436 rxa00886 1269 GBBA1:SYCSLLLH 132106 GBBA1:SCDNAJ 5611 GBBA1:STMDNAK 4648 rxaOO900 975 GB 8A2:ECOUW67 0 110000 GB_8A2:ECOUW67_0 110000 GB BA2:AE000393 10516 rxaOO9Ol 537 GB-HTG3:AC010757 175571 AL035591 N96610 T45493 064006 X77458 146700 U 18997 U 18997 AE000393 AC010757 GBHTG3:AC010757 175571 AC010757 GBHTG3:ACO11283 87295 AC01 1283 rxaOO98l 753 GB -OV:GGA245664 512 AJ245664 GB-PL2:AC007887 159434 AC007887 GB-GSS1 :CNSOORNW 542 AL087338 rxa00995 864 GB-EST29:A1553951 450 A1553951 GB-PR3:AC003029 139166 AC003029 Streptomyces coelicolor cosmid C54. Streptomyces coelicolor 21285 Lambda-PRL1I Arabidopsis thaliana cDNA clone FIOG3T7, rnRNA Arabidopsis thaliana 8756 Lambda-PRL-2 Arabidopsis thaliana cDNA clone 133C14T7, mRNA Arabidopsis thaliana Synechocystis sp. PCC6803 complete genome, 25/27, 31 38604-3270709. Synechocystis sp.
Scoellcolor dnaK, grpE and dnaJ genes. Streptomyces coelicolor Streptomyces coelicolor (strain A3(2)) dnaK operon encoding molecular Streptomyces coelicolor chaperones (dnaK, dnaJ). grpE and hspR genes. complete cds's.
Escherichia col K-12 chromosomal region from 67.4 to 76.0 minutes. Escherichia coli Escherichia coli K-12 chromosomal region from 67.4 to 76.0 minutes. Escherichia coli Escherichia coli K-12 MG1655 section 283 of 400 of the complete genome. Escherichia coi Home sapiens chromosome 18 clone 128C_18 map 18. SEQUENCING IN Homo sapiens PROGRESS 20 unordered pieces Home sapiens chromosome 18 ctone 128C_18 map 18, SEQUENCING IN Homo sapiens PROGRESS 20 unordered pieces.
Home sapiens clone MS2016A09. SEQUENCING IN PROGRESS 1 Home sapiens unordered pieces.
Gallus gallus partial mRNA for ATP-citrate lyase (ACL gene). Gallus gatlus Genomic sequence for Arabidopsis thatiana BAC F1504 from chromosome 1. Arabidopsis thaliana complete sequence, Arabidopsis thatiana genome survey sequence T7 end of SAC F1 4D7 of IGF Arabidopsis thaliana library from strain Columbia of Arabidopsis thaliana, genomic survey sequence.
teS4d0l xl SoaresNFLTGBC Si Home sapiens cDNA clone IMAGE:2090497 Home sapiens 3 similar to gb:X02067 H.sapiens mRNA for 7SL RNA pseudogene (HUMAN);, rnRNA sequence.
Homo sapiens Chromosome 12q24 PAC RPCI3-462E2 (Roswell Park Cancer Home sapiens Institute Human PAC library) complete sequence.
Erwinia amylovora srlA, srtE, srlB, srlD, srIM and srlR genes. Erwinia amnylovora Archaeoglobus fulgidus section i06 of 172 of the complete gename. Archaeoglobus fulgidus AV0l 8764 Mus musculus 18-day embryo C57BI6J Mus musculus cDNA clone Mus musculus 1190006M16, mRNA sequence.
39,602 37,801 34,194 37,459 49,744 49,583 38,314 37,759 38,314 34,857 11 -Jun.99 5-Jan-98 4-Aug-98 13-Feb-99 21-Nov-96 22-Nov-96 ItI U18997 C U18997 12-Nov-98 22-Sep-99 34.857 22-Sepo-99 35,448 07-OCT-i1999 37,538 28-Sep-99 37.600 04-OCT-i1999 4 1.264 28-Jun-99 42.627 13-Apr-99 38.915 17-Sep-98 37.694 8-Jan-98 GB-BA1:EAY14603 rxca00996 864 GB-BA2:AEOIOO1 GB-EST3:AVO1 8764 4479 Y14603 10730 AEQ01001 242 AV01 8764 4 1.078 39.669 1 5-DEC-1997 28-Aug-99 GB_GSS3:B24189 377 B241 89 rxaOI0lO 1242 GBOVAF007068 356 AF007068 GBEST1O:AA166324 514 AA166324 GB-EST7:W89968 46 W89968 732 GBGSS12AQ381423 579 AQ381423 GB-HTG6:AC01 0901 206121 AC01 0901 GBGSS5:AQ746932 837 A0746932 rxaOlOS2 432 GBINI:CELC13D9 43487 AF016420 GBIlN1:CELC13D9 43487 AF016420 rxa0l 053 543 GBOV:CHKMAFG1 1316 D2B601 GB-HTG6:AC010765 146468 AC010765 GBHTG6:AC010765 146468 AC01 0765 rxa01054 612 GB-PL1:PHNPNGLP 962 D45425 GB-HTG2:HSJ402N21 170302 AL049553 GB-HTG2:HSJ402N21 170302 AL049553 rxa0l2l7 723 GBJIN2:CELF18A12 29784 AF016688 GB.!N2:CELF18A12 29784 AF0166B8 GB-RO:MUSMCFrR 6304 M60493 rxa0l32O 1770 GBBA2:AF031037 1472 AF031037 GB-HTG1 :PFMAL13PA8OS18 AL109815 GB-HTG1:PFMALI 3PA8051 8 AL1 09815 rxa~l 345 1575 GB-PR3:AC005224 166687 AC005224 GB-PR3:AC005224 166687 AC005224 GBHTG3:AC01 1500_1300851 AC01 1500 rxa~l 407 1014 GB-HTG3:AC01 0831 70233 AC01 0831 Table 4 (continued) F19E I6TF IGF Arabidopsis thaliana genomic clone Fl 9E16. genomic survey Arabidopsis thaliana sequence.
Coturnix cotumix arylalkylamine N-acetyltransferase mRNA. partial ods. Coturnix cotumix ms50c09.r1 Life Tech mouse embryo 13 Sdpc 10666014 Mus musculus cDNA Mus musculus clone IMAGE:614992 5' similar to SW:NEST RAT P2 1263 NESTIN. mRNA sequence.
mf64gll.rl Soares mouse embryo NbME113.5 14.5 Mus musculus cONA clone Mus musculus IMAGE:419108 5' similar to SW:NEST RAT P21263 NESTIN rnRNA sequence.
RPCI1 1 -135F1 D.TJ RPCI-1 I Homo sapiens genomic cdone RPCI-1 1 -135F10, Homo sapiens genomlc survey sequence.
Homo sapiens clone RP1 1-544J22, WORKING DRAFT SEQUENCE. 1 unordered Homo sapiens 44. 385 46.629 38,677 1 0-OCT-1 997 12-Jul-97 19-DEC-1996 58,696 12-Sep-96 pieces.
HS_5538_AlAll _T7A RPCI-1 1 Human Male BAC Library Homo sapiens genomic clone Plate= 1114 Coi=2 1 Row=A, genomic; survey sequence.
Caenorhabditis elegans cosmid Cl 31D9.
Caenortiabditis elegans cosmid Cl 3D9.
Chicken novel maf-related gene mafG encoding bZip nuclear protein MafG, promoter region and exon 1.
Homo sapiens clone RP1 1-1 15N6. SEQUENCING IN PROGRESS ~,26 unordered pieces.
Homo sapiens clone RPl 1-1 15N6, SEQUENCING IN PROGRESS ,26 unordered pieces.
Pharbitis nil mRNA for Pharbitis nil Germin-like protein precursor, complete cds.
Homo sapiens chromosome 6 clone RP3-402N21 map p21.1-211 31, -SEQUENCING IN PROGRESS in unordered pieces.
H-omo sapiens chromosome 6 clone RP3-402N21 map p21.1-21.31, -SEQUENCING IN PROGRESS-. in unordered pieces.
Caenorhabditis elegans cosmid F18BA12.
Ceenorhabditis elegans cosmid Fl 8A1 2.
Mouse cystic fibrosis transmembrane conductance regulator (CFTR) mRNA, complete cds.
Neisseria meningitidis chioramphenicol acetyltransferase gene, complete cds.
Plasmodiumn falciparumn chromosome 13 strain 3D7, -SEQUENCING IN PROGRESS in unordered pieces.
Plasmodium falciparum chromosome 13 strain 3D?, -SEQUENCING IN PROGRESS in unordered pieces.
Homo sapiens chromosome 17, clone hRPK.2140 complete sequence.
Homo sapiens chromosome 17, clone hRPK.21401, complete sequence.
Homo sapiens chromosome 19 coeCIT978SKB6E1, SEQUENCING IN PROGRESS 246 unordered pieces.
Homo sapiens clone 6L_24, LOW-PASS SEQUENCE SAMPLING.
Homo sapiens Caenorhabditis elegans Caenorhabditis elegans Gallus gallus Homo sapiens Homo sapiens tpomoea nil Homo sapiens Homo sapiens Caenorhabditis elegans Caenorhabditis elegans Mus musculus Neisseria menlngitidis Plasmodium talciparum Plasmodium falciparumn Homo sapiens Homo sapiens Homo sapiens Homo sapiens 37.651 36,011 38,640 39,344 38,780 39,205 32,961 38,476 42,925 38,825 36,825 35.794 40,625 37,793 35,014 17,697 17,697 38,195 36,611 36,446 35,764 21-MAY-i1999 04-DEC-I1999 1 9-Jul-99 2-Aug.97 2-Aug-97 7-Feb-99 07-OEC-1 999 07-DEC.1999 10-Feb-99 03-DEC-i1999 03-DEC-i1999 08-OCT-i1999 08-OCT-i1999 10-Jun-94 21-Apr-98 19-Aug-99 1 9-Aug-99 14-Aug-98 14-Aug-98 AC01 1500 23-Sep-99 GBIITG3:AC010831 GB-PR3AC004058 rxa0l4OB 324 GBPR4AF152365 GBHTG3:ACOO7BSO 70233 AC01 0831 38400 AC004058 246545 AF152365 121256 AC007890 GBHTG3;AC007890 121256 AC007890 rxa01524 1566 GBBA1:BSUBOO15 218410 Z99118 GB-HTG2:AC008260 107439 AC008260 GBHTG2:AC008260 107439 AC008260 rxa0lS78 1510 GBPR4:AF 111170 GB,,PR4:AFI 111170 GBBA1:AEY13732 nxa0l6l6 1605 GB-BA2:AF088857 GB INi :CEMO4D8 GB-EST25:A281 910 148083 AF111170 148083 AF111170 6740 Y13732 2908 21552 276 AF088857 Z32682 A128 1910 Table 4 (continued) Homo sapiens clone 6_-L_24. LOW-PASS SEQUENCE SAMPLING.
Homo sapiens chromosome 4 clone B241P1 9 map 4q25. complete sequence.
Homo sapiens constitutive fragile region FRA3B sequence.
Drosophila n'elanogaster chromosome 3 clone BACRO2G21 (D722) RPCI-98 02.G.21 map 90E-91A strain y; cn bw sp, SEQUENCING IN PROGRESS~, 89 unordered pieces.
Drosophila melanogaster chromosome 3 clone BACRO2G21 (0722) RPCI-98 02.G.21 map 90E-91A strain y; cn bw sp, SEQUENCING IN PROGRESS~, 89 unordered pieces.
Bacillus subtilis complete genome (section 15 of 21): from 2795131 to 3013540.
Drosophila melanogaster chromosome 2 clone BACR13J1O (0924) RPCI-98 13.J.10 map 47B3-47C strain y: cn bw sp, -SEQUENCING IN PROGRESS~, 82 unordered pieces.
Drosophila melanogaster chromosome 2 clone BACR13JIO (0924) RPCI-98 13.J.10 map 47B-47C strain y; cn bw sp. SEQUENCING IN PROGRESS 82 unordered pieces.
Homo sapiens 14q32 Jagged2 gene, complete cds; and unknown gene.
Homo sapiens 14q32 Jagged2 gene, complete cds; and unknown gene.
Alcaligenes eutrophus genes for ureases. ureDi, ureD2, ureA, ureB. and ORFi, ORF2.
Vogesella indigofera indigoidine biosynthesis regulatory locus, complete Caenorhabditis elegans cosmid M04D8, complete sequence.
qt82d04.xl NCI_-CGAP_Col14 Homo sapiens cDNA clone IMAG E: 1961767 3T.
mRNA sequence.
Corynebacterium glutamicurn mullidrug resistance protein (crnr) gene, complete cds.
Drosophila melanogaster chromosome 3 clone BACRO9F18 (D612) RPCI-98 09.F.1 8 map 980-980 strain y; cn bw sp, SEQUENCING IN PROGRESS 109 unordered pieces.
Drosophila melanogasler chromosome 3 clone BACR09F18 (0812) RPCI-98 09.F.18 map 98D-98D strain y; cn bw sp,~ SEQUENCING IN PROGRESS--, 109 unordered pieces.
Daucus carota mRNA for citrate synthase. complete cds.
Homo sapiens endothelial nitric oxide synthase gene, complete cds.
Homo sapiens clone NH01 66023, SEQUENCING IN PROGRESS 7 unordered pieces.
Homo sapiens chromosome 9 clone 30_C_-23 map 9. SEQUENCING IN PROGRESS 20 unordered pieces.
Homo sapiens Chromosome 9 clone 30_-C_-23 map SEQUENCING IN PROGRESS 20 unordered pieces.
Homo sapiens clone 1 15_L23, LOW-PASS SEQUENCE SAMPLING.
Ecoli protein p7 (neu C) gene, complete cds.
-omo sapiens Hlomo sapiens Ralstonia eutropha Jogesella indigofera Caenorhabditis elegans Homo sapiens 37,873 40.220 42,960 37.626 37,237 38,406 lomo sapiens 35,764 Homo sapiens 40,778 lomo sapiens 41,234 )rosophila melanogaster 39,432 Drosophila melanogaster 39,432 Bacillus subtilis 38,201 Drosophila melanogaster 38,302 Drosophila melanogaster 38,302 23-Sep-99 30-Sep-96 1-Aug-99 3-Sep-99 3-Sep-99 26-Nov-97 2-Aug-99 2-Aug-99 14-Jul-99 14-Jul-99 23-Sep-97 110-Sep-99 23-Nov-98 21-DEC-1998 rxa01666 1500 GB,,BA1:CGU43535 2531 U43535 GBHTG3:AC009213 114735 AC009213 GB-HTG3:AC009213 114735 AC009213 rxa01674 1017 GBPL1:AB017159 1859 ABO17159 GBPR1:HUMGN054823142 026607 GBHTG3:AC01 1234 154754 AC01 1234 rxa01873 1359 GB-HTG3:AC009450 124337 AC009450 GBt-ITG3AC009450 124337 AC009450 GB-HTG3:AC009919 134724 AC009919 rxa01922 1275 GB_BA1:ECONEUC 1676 M84026 Corynebacterium 99,933 9-Apr-97 ~lutamnicurn Drosophila melanogaster 36.111 Drosophila melanogaster 36,111 Daucus carota 39.537 Homo sapiens 36,419 Homo sapiens 36.317 Homo sapiens 35,303 Homo sapiens 35,303 23-Aug-99 23-Aug-99 01-MAY-i1999 04-OCT-i1999 22-Aug-99 Homo sapiens 35,409 8-Sep-99 Escherichia coli 35,189 26-Apr-93 GB-HTG2:AC007853 116280 AC007853 GB-HTG2:AC007853 116280 AC007853 rxa01936 1395 GB-HTG4:ACOIOO37 166249 AC010037 GB-HTG4:ACO10037 166249 Ac010037 GIB PR4:AC005552 167228 AC005552 rxa0l984 420 GBPR1:HS169C8F 245 Z57239 GBBA1:SERATTBXIS 3255 11 1597 GB-EST7:W97557 267 W97557 Table 4 (continued) Drosophila melanogaster chromosome 3 clone BACR03LC02 (0766) RPCI-98 031L.2 map 9613-96C strain y; cn bw sp, SEQUENCING IN PROGRESS 80 unordered pieces.
Drosophila melarrogaster chromosome 3 clone BACR03LO02 (0766) RPCI-98 03.1.2 map 968-960 strain y; cn bw sp, **SEQUENCING IN PROGRESS-, unordered pieces.
Drosophila melanogaster chromosome 3116686 clone RPCI9M-E4, SEQUENCING IN PROGRESS -,52 unordered pieces.
Drosophila melanogaster chromosome 3lJ66B6 clone RPCI98-6E4, SEQUENCING IN PROGRESS 52 unordered pieces.
Homo sapiens chromosome 17, clone hRPK.212E 8, complete sequence.
H sapiens CpG island DNA genomic Msel fragment, clone 169c8, forward read cpgl69c8.ftla.
Saccharopolyspora erythraea excislonase (xis) gene. integrase (int) gene, complete cds's and attB site.
mf98a09.r1 Soares mouse embryo NbME 13.5 14.5 Mus musculus cDNA clone IMAGE 422296 mRNA sequence.
Drosophila melanogaster 34,365 Drosophila melanogaster 34.365 Drosophila melanogaster 38,534 Drosophila melanogaster 38,534 2-Aug-99 0 2.Aug.99 16-OCT-i1999 16-OCT-1999 Homo sapiens Homo sapiens Sacctiaropolyspora erythraea Mus musculus rxa02O6O rxa02087 1470 GBPR3:AC005544 GBPL1:ATF2OB18 169045 AC005544 Homo sapiens chromosome 17, clone hRPK.349_A 8, complete sequence.
104738 AL049483 Arabidopsis thaliana DNA chromosome 4, BAC clone F201318 (ESSA project).
Homo sapiens Arabidopsis thaliana G13PL2ATT25K17 89904 AL049171 rxa02088 1338 GBI-ITG3:AC008697 167932 AC008697 GB-HTG3:AC008697 167932 AC008697 GBHTG3:AC008703 213971 AC008703 rxeO2lS9 636 GBBA2:AF049897 9196 AF049897 GB-BA2:AF031518 2045 AF031518 GB-BA2:AF041436 516 AF041436 rxa02184 504 GBBA1:B5Z92953 8164 Z92953 GB-EST36:A878071 593 A1878071 Arabidopsis thaliana DNA chromosome 4, BAC clone (ESSA project). Arabidopsis thaliana Homo sapiens chromosome 5 clone CIT978SKB-7003, SEQUENCING IN Homo sapiens PROGRESS 54 unordered pieces.
Homo sapiens chromosome 5 clone CIT978SKB_70D3, SEQUENCING IN Homo sapiens PROGRESS 54 unordered pieces.
Homo sapiens chromosome 5 clone CIT978SKB_76P12, SEQUENCING IN H-omno sapiens PROGRESS 54 unordered pieces.
Corynebacterium glutamicum N-acelylglutamnylphosphate reductase (argC), Corynebactenium ornithine a cetyltra nsfe rase (argJ), N-acetylgl uta mate kinase (argB), acetylornithine glutamicumn transaminase (argD), ornithine carbamoyltransferase (argF), arginine repressor (argR), argininosuccinale synthase (argG), and argininosuccinate lyase (argH) genes, complete cds.
Corynebacterium glutamicum ornithine ca rbamo lytra nsfe rase (argF) gene, Corynebacteriumn complete cds. glutamnicumn Corynebacterium glutamicum arginine repressor (argR) gene, complete cds. Corynebacterium 36,249 26-Nov-98 45,679 18-OCT-1995 36,232 6-Jul-94 42,969 16-Jul-96 35,724 25-Sep-98 35,890 24-NMAR-i1999 38,128 27-Aug-99 36,662 3-Aug.99 36.662 3-Aug.99 34,768 3-Aug-99 99,843 1-Jul-9 88,679 5-Jan-99 100,000 5-Jan-99 38,951 24-Jun-98 36,774 21-Jul-99 B.subtilis yws[A,B,C) genes and rbs[A,C,D.K,R] genes.
fcS7al2.yl Zebrafish WashU MPIMG EST Danio rerlo cDNA 5 similar to TR:01 3151 013151 HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN AO :mRNA sequence.
glutamicum Bacillus subtilis Danio rerie GB-EST37:A1958166 641 A1958166 rxa02200 1233 GBPR3:HSA494016 GB-HTG2:AC008161 GB-HTG2:ACOO8 161 rxa02201 486 GBEST4:H16949 GB_-EST4:H16949 rxa02202 762 GBINl:CELC41A3 GB-EST33:AV0801 51 GBGSS5:AQ768877 rxa02205 1002 GB-HTG2:AC005959 GB8HTG2:AC005959 G13IN1 :BRPTUEIBA rxa02305 975 GB RO:MUSPAFR GBPR3:HUMARL1A GB BA1 :MLCB2533 rxa02431 899 GB-EST4:H35255 GBHTG1:HS791K14 GB-HTGI:HS791K14 rxs02446 558 GB-BA2:AF036166 GB-EST5:N251 22 GB-EST5:N251 22 rxa02541 1308 GB-BA2:DPU93358 GBEST3O:A1658096 GB-EST37:A1959242 50502 158440 158440 465 465 37149 236 545 127587 127587 4571 1140 1008 40245 407 1155318 155318 895 620 620 1267 343 545 A117328 AC008161 AC008 161 H 16949 H1 6949 U41541 AV080151 AQ766877 ACG05959 AC005959 M36380 D50872 L28997 AL03531 0 H35255 AL035685 AL035685 AF036166 N25122 N25122 U93358 A1658096 A1959242 Table 4 (continued) fc9l (01 .yl Zebrafish WashU MVPIMG EST Danlo rerio cDNA 5'similar to lDanio rerio TR:013151 013151 HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN AO :mRNA sequence.
Human DNA sequence from clone 494016 on chromosome 22, complete Homo sapiens sequence.
Mus musculus clone 182_H_5, SEQUENCING IN PROGRESS ~,29 Mus musculus unordered pieces.
Mus musculus clone 182_H_5, SEQUENCING IN PROGRESS ~,29 Mus musculus unordered pieces.
ym34al1.r0 Soares infant brain I NIB Homo sapiens cDNA clone IMAGE:50010 Homo sapiens mRNA sequence.
ym34allr1. Soares infant brain INIB Homo sapiens cONA clone IMAGE:50010 5',-Homo sapiens mRNA sequence.
36,774 20-Aug-99 38.648 23-Nov-99 Caenorhabdltls elegans cosmid C41A3.
AV060151 Mus musculus stomach C57B1J6J adult Mus musculus cDNA clone 2210413B04, mRNA sequence.
HS_2017_B2_B08_MR CIT Approved Human Genomic Sperm Library D Homo sapiens genomic clone Plale=2017 CotI=16 Row=D, genomic survey sequence.
Homo sapiens, SEQUENCING IN PROGRESS ordered pieces.
Homo sapiens, SEQUENCING IN PROGRESS ,2 ordered pieces.
B.pahangi beta-tubulin gene, complete cds.
Mouse gene for platelet activating factor receptor, complete cds.
Homo sapiens ARLI mRNA, complete eds.
Mycobacterium leprae cosmid B2533.
EST1 11890 Rat PC-12 cells, NGF-Ireated (9 days) Rattus sp. cDNA clone RPNCOO3, mRNA sequence.
Homo sapiens chromosome 20 clone RP4-791 K14. SEQUENCING IN PROGRESS In unordered pieces.
Homo sapiens chromosome 20 clone RP4-79i Ki 4. SEQUENCING IN PROGRESS in unordered pieces.
Xanthomonas campestris organic hydroperoxide resistance protein (ohr) gene, complete cds.
yxlgdlO.rl Soares melanocyle 2NbHM Homo sapiens cONA clone IMAGE:262195 5, mRNA sequence.
yxi 9dlo0.0 Soares melanocyte 2NbHM Homo sapiens cDNA clone IMAGE:262195 mRNA sequence.
Deinococcus proleolylicus 40 kDa heat shock chaperone protein (dnaJ) gene.
complete cds, fc14c09.yl Zebrafish WashU MPIMVG EST Danio rerio cDNA 5' similar to SW:DNJ2_HUMAN P31689 DNAJ PROTEIN HOMOLOG 2. mRNA sequence.
fd25h1 I.yl Zebrafish WashU MPIMG EST Danio rerio cONA 5 similar to SW:DNJ2-HUMAN P31 689 ONAJ PROTEIN HOMOLOG 2. mRNA sequence.
Caenorhabditis elegans Mus musculus Homo sapiens Homo sapiens Homo sapiens Brugla pahangi Mus musculus Homo sapiens Mycobacterium lepre Rattus sp.
Homo sapiens Homo sapiens Xanthomonas campestris Homo sapiens Homo sapiens Deinococcus proteolyticus Danio rerio Danio rerio 35,938 35.938 38,267 36,552 41.678 43,348 35,568 40,310 40,310 37,703 38,420 42,188 42,000 39.098 39,456 39,456 49,369 35,417 37.172 42,115 52,059 28-Jul-99 28-Jul-99 29-Jun-95 29-Jun-95 08-DE C-i1995 25-Jun-99 28-Jul-99 11-Nov-98 I 1 1-Nov-98 c 26-Apr-93 I 10-Feb-99 13-Jan-95 27-Aug-99 2-Apr-98 23-Nov-99 23-Nov-99 19-MAY-1998 28-DEC-i 995 28-DEC-I1995 17-Jan-98 06-MAY-1 999 45,438 20-Aug-99 Table 4 (continued) DNA encoding Dnak protein which is one of heat shock protein from rxa02542 777 EM PATE1 0832 1856 E10832 Corynebacterium glutamicum GB-EST24:Z82017 396 GBOM:CATERYTHRO68l rxa02543 1977 EMPAT:E10832 1856 Z82017 SSZ82017 Porcine small intestine cDNA library Sus scrofa cDNA clone c12c06 5' Sus scrofa similar to eukaryotic initiation factor 4 gamma, mRNA sequence.
Li10606 Cat erythropoietin mRNA, 3' end. Felis catus E10832 DNA encoding Dnak protein which is one of heat shock protein from Corynebact 99,000 08-OCT-i1997 (Rel. 52, Created) 37,067 30-Apr-99 39.409 14-OCT-1993 97,306 08-OCT-1997 (Rel. 52, Created) erium glutamicum GB-BA1:MPHSP7O 2179 X59437 M.paratuberculosis gene for 70 kD heat shock protein.
GB-BA1:MTY13E1O 35019 Z95324 Mycobacterium tuberculosis H37Rv complete genome; segment 18/162.
rxa02586 393 GB_1N2:AC006472 156362 AC006472 GByTG4:AC010020 106541 AC010020 GB-HTG4:AC010020 106541 AC010020 rxa02587 2214 GBBAI:MLCL622 GBRO:AF074879 GB-R0:RNJOOI 380 rxs03217 331 GB SAl :MLCB2S48 42498 3316 2641 38916 Z95398 AF074879 AJO0 1380 AL023093 AL079336 Drosophila melanogaster, chromosome 2R, region 45E1-46A2, BAC clone BACR48G21, complete sequence.
Drosophila melanogaster chromosome 31J66D10 done RPC198-2613, SEQUENCING IN PROGRESS 55 unordered pieces.
Drosophila melanogaster chromosome 31J66D1 0 clone RPCI98-2613, SEQUENCING IN PROGRESS 55 unordered pieces.
Mycobacterium leprae cosmid L622.
Rattus norvegicus testis-specific protein TSPY gene, complete cds.
Rattus norvegicus Tspy partial genomic sequence, exons 1-6.
Mycobacterium leprae cosmid B2W4.
Homo sapiens chromosome 20 clone RP4-662M14, SEQUENCING IN PROGRESS 10 unordered pieces.
Home sapiens chromosome 20 clone RP4-562M14, -SEQUENCING IN PROGRESS-', 10 unordered pieces.
Mycobactenum avium 73,404 subsp. paratuberculosis Mycobactenum 72,028 tuberculosis Drosophila melanogaster 37,958 Drosophila melanogaster 37,333 Drosophila melanogaster 37.333 17-Jun-98 30-Jan-99 16-OCT-i 999 16-OCT-1 999 23-Apr-92 Mycobacterlum leprae Rattus norvegicus Rattus norvegicus Mycobacterium leprae Homo sapiens Home sapiens 39,848 35.830 37,702 37,888 36.420 24-Jun-97 6-Jul-gg 29-Jun-98 27-Aug-99 4-Feb-00 GBHTG2:HSJ662M14 174772 GB-HTG2:HSJ652Ml4 174772 AL079336 35,962 4-Feb-00 WO 01/00804 PCT/IB00/00922 -86- Exemplification Example 1: Preparation of total genomic DNA of Corynebacterium glutamicum ATCC 13032 A culture of Corynebacterium glutamicum (ATCC 13032) was grown overnight at 30 0 C with vigorous shaking in BHI medium (Difco). The cells were harvested by centrifugation, the supernatant was discarded and the cells were resuspended in 5 ml buffer-I of the original volume of the culture all indicated volumes have been calculated for 100 ml of culture volume). Composition of buffer-I: 140.34 g/l sucrose, 2.46 g/l MgSO, x 7H,O, 10 ml/I KH 2 PO, solution (100 g/l, adjusted to pH 6.7 with KOH), 50 ml/1 M12 concentrate (10 g/l (NHl),SO,, 1 g/l NaCI, 2 g/1 MgSO, x 7H 2 0, 0.2 g/l CaCI 2 0.5 g/l yeast extract (Difco), 10 ml/l trace-elements-mix (200 mg/l FeSO.
x H 2 0, 10 mg/1 ZnSO, x 7 HO, 3 mg/l MnCI, x 4 H,O, 30 mg/1 H,BO, 20 mg/1 CoCI, x 6 H 2 0, I mg/I NiCI, x 6 H 2 O, 3 mg/l Na,MoO, x 2 H 2 0, 500 mg/l complexing agent (EDTA or critic acid), 100 ml/1 vitamins-mix (0.2 mg/I biotin, 0.2 mg/l folic acid, mg/l p-amino benzoic acid, 20 mg/1 riboflavin, 40 mg/l ca-panthothenate, 140 mg/1 nicotinic acid, 40 mg/l pyridoxole hydrochloride, 200 mg/l myo-inositol). Lysozyme was added to the suspension to a final concentration of 2.5 mg/ml. After an approximately 4 h incubation at 37°C, the cell wall was degraded and the resulting protoplasts are harvested by centrifugation. The pellet was washed once with 5 ml buffer-I and once with 5 ml TE-buffer (10 mM Tris-HC1, 1 mM EDTA, pH The pellet was resuspended in 4 ml TE-buffer and 0.5 ml SDS solution and 0.5 ml NaCI solution (5 M) are added. After adding ofproteinase K to a final concentration of 200 .g/ml, the suspension is incubated for ca.18 h at 37 0 C. The DNA was purified by extraction with phenol, phenol-chloroform-isoamylalcohol and chloroformisoamylalcohol using standard procedures. Then, the DNA was precipitated by adding 1/50 volume of 3 M sodium acetate and 2 volumes of ethanol, followed by a 30 min incubation at -20 0 C and a 30 min centrifugation at 12,000 rpm in a high speed centrifuge using a SS34 rotor (Sorvall). The DNA was dissolved in 1 ml TE-buffer containing pg/ml RNaseA and dialysed at 4 0 C against 1000 ml TE-buffer for at least 3 hours.
During this time, the buffer was exchanged 3 times. To aliquots of 0.4 ml of the dialysed DNA solution, 0.4 ml of 2 M LiCI and 0.8 ml of ethanol are added. After a 87 min incubation at -20 0 C, the DNA was collected by centrifugation (13,000 rpm, Biofuge Fresco, Heraeus, Hanau, Germany). The DNA pellet was dissolved in TE-buffer. DNA prepared by this procedure could be used for all purposes, including southern blotting or construction of genomic libraries.
Example 2: Construction of genomic libraries in Escherichia coli of Corynebacterium glutamicum ATCC13032 Using DNA prepared as described in Example 1, cosmid and plasmid libraries were constructed according to known and well established methods (see Sambrook, J. et al. (1989) "Molecular Cloning A Laboratory Manual", Cold Spring Harbor Laboratory Press, or Ausubel, F.M. et al. (1994) "Current Protocols in Molecular Biology", John Wiley Sons).
Any plasmid or cosmid could be used. Of particular use were the plasmids pBR322 (Sutcliffe, J.G. (1979) Proc. Natl. Acad. Sci. USA, 75:3737-3741); pACYC177 (Change Cohen (1978) J. Bacteriol 134:1141-1156), plasmids of 15 the pBS series (pBSSK+, pBSSK- and others; Stratagene LaJolla USA), or cosmids as SuperCosl (Stratagene, LaJolla, USA) or Lorist6 (Gibson, T.J., Rosenthal A. and Waterson, R.H. (1987) Gene 53:283-286. Gene libraries specifically for use in C. glutamicum may be constructed using plasmid pSL109 (Lee, and A.J. Sinskey (1994) J. Microbiol. Biotechnol. 4: 256-263).
S 20 Example 3: DNA Sequencing and Computational Functional Analysis 6* Genomic libraries as described in Example 2 were used for DNA sequencing according to standard methods, in particular by the chain termination method using AB1377 sequencing machines (see Fleischman, R.D. et al.
(1995) "Whole-genome Random Sequencing and Assembly of Haemophilus 25 Influenzae Rd., Science, 269:496-512). Sequencing primers with the following nucleotide sequences were used: 5'-GGAAACAGTATGACCATG-3' (SEQ ID NO.
305) or 5'-GTAAAACGACGGCCAGT-3' (SEQ ID NO. 306).
Example 4: In vivo Mutagenesis In vivo mutagenesis of Corynebacterium glutamicum can be performed by passage of plasmid (or other vector) DNA through E. coil or other microorganisms Bacillus spp. or yeasts such as Saccharomyces cerevisiae) which are impaired in their capabilities to maintain WO 01/00804 PCT/IB00/00922 -88the integrity of their genetic information. Typical mutator strains have mutations in the genes for the DNA repair system mutHLS, mutD, mutT, etc.; for reference, see Rupp, W.D.
(1996) DNA repair mechanisms, in: Escherichia coli and Salmonella, p. 2277-2294, ASM: Washington.) Such strains are well known to those of ordinary skill in the art. The use of such strains is illustrated, for example, in Greener, A. and Callahan, M. (1994) Strategies_7: 32-34.
Example 5: DNA Transfer Between Escherichia coli and Corynebacterium glutamicum Several Corynebacterium and Brevibacterium species contain endogenous plasmids (as pHMI519 or pBLI) which replicate autonomously (for review see, e.g., Martin, J.F. et al. (1987) Biotechnology, 5:137-146). Shuttle vectors for Escherichia coli and Corynebacterium glutamicum can be readily constructed by using standard vectors for E. coli (Sambrook, J. el al. (1989), "Molecular Cloning: A Laboratory Manual", Cold Spring Harbor Laboratory Press or Ausubel, F.M. et al. (1994) "Current Protocols in Molecular Biology", John Wiley Sons) to which a origin or replication for and a suitable marker from Corynebacterium glutamicum is added. Such origins of replication are preferably taken from endogenous plasmids isolated from Corynehacterium and Brevibacterium species. Of particular use as transformation markers for these species are genes for kanamycin resistance (such as those derived from the Tn5 or Tn903 transposons) or chloramphenicol (Winnacker, E.L. (1987) "From Genes to Clones Introduction to Gene Technology, VCH, Weinheim). There are numerous examples in the literature of the construction of a wide variety of shuttle vectors which replicate in both E.
coli and C. glutamicum, and which can be used for several purposes, including gene overexpression (for reference, see Yoshihama, M. et al. (1985) J. Bacteriol. 162:591-597, Martin J.F. et al. (1987) Biotechnology, 5:137-146 and Eikmanns, B.J. et al. (1991)Gene, 102:93-98).
Using standard methods, it is possible to clone a gene of interest into one of the shuttle vectors described above and to introduce such a hybrid vector into strains of Corynebacterium glutamicum. Transformation of C glutamicum can be achieved by protoplast transformation (Kastsumata, R. et al. (1984) J. Bacteriol. 159306-311), electroporation (Liebl, E. et al. (1989) FEMS Microbiol. Letters, 53:399-303) and in cases where special vectors are used, also by conjugation (as described e.g. in Schafer, A et al.
WO 01/00804 PCT/IB00/00922 -89- (1990) J. Bacteriol. 172:1663-1666). It is also possible to transfer the shuttle vectors for C. glutamicum to E. coli by preparing plasmid DNA from C. glutamicum (using standard methods well-known in the art) and transforming it into E. coli. This transformation step can be performed using standard methods, but it is advantageous to use an Mcr-deficient E. coli strain, such as NM522 (Gough Murray (1983) J. Mol. Biol. 166:1-19).
Genes may be overexpressed in C. glutamicum strains using plasmids which comprise pCGI Patent No. 4,617,267) or fragments thereof, and optionally the gene for kanamycin resistance from TN903 (Grindley, N.D. and Joyce, C.M. (1980) Proc. Natl. Acad Sci. USA 77(12): 7176-7180). In addition, genes may be overexpressed in C. glutamicum strains using plasmid pSL109 (Lee, and A. J.
Sinskey (1994) J Microbiol. Biotechnol. 4: 256-263).
Aside from the use of replicative plasmids, gene overexpression can also be achieved by integration into the genome. Genomic integration in C. glutamicum or other Corynebacterium or Brevibacterium species may be accomplished by well-known methods, such as homologous recombination with genomic region(s), restriction endonuclease mediated integration (REMI) (see, DE Patent 19823834), or through the use of transposons. It is also possible to modulate the activity of a gene of interest by modifying the regulatory regions a promoter, a repressor, and/or an enhancer) by sequence modification, insertion, or deletion using site-directed methods (such as homologous recombination) or methods based on random events (such as transposon mutagenesis or REMI). Nucleic acid sequences which function as transcriptional terminators may also be inserted 3' to the coding region of one or more genes of the invention; such terminators are well-known in the art and are described, for example, in Winnacker, E.L. (1987) From Genes to Clones Introduction to Gene Technology. VCH: Weinheim.
Example 6: Assessment of the Expression of the Mutant Protein Observations of the activity of a mutated protein in a transformed host cell rely on the fact that the mutant protein is expressed in a similar fashion and in a similar quantity to that of the wild-type protein. A useful method to ascertain the level of transcription of the mutant gene (an indicator of the amount of mRNA available for translation to the gene product) is to perform a Northern blot (for reference see, for example, Ausubel et al.
WO 01/00804 PCT/IB00/00922 (1988) Current Protocols in Molecular Biology, Wiley: New York), in which a primer designed to bind to the gene of interest is labeled with a detectable tag (usually radioactive or chemiluminescent), such that when the total RNA of a culture of the organism is extracted, run on gel, transferred to a stable matrix and incubated with this probe, the binding and quantity of binding of the probe indicates the presence and also the quantity ofmRNA for this gene. This information is evidence of the degree of transcription of the mutant gene. Total cellular RNA can be prepared from Corynebacterium glutamicum by several methods, all well-known in the art, such as that described in Bormann, E.R. et al.
(1992) Mol. Microbiol. 6: 317-326.
To assess the presence or relative quantity of protein translated from this mRNA, standard techniques, such as a Western blot, may be employed (see, for example, Ausubel et al. (1988) Current Protocols in Molecular Biology, Wiley: New York). In this process, total cellular proteins are extracted, separated by gel electrophoresis, transferred to a matrix such as nitrocellulose, and incubated with a probe, such as an antibody, which specifically binds to the desired protein. This probe is generally tagged with a chemiluminescent or colorimetric label which may be readily detected. The presence and quantity of label observed indicates the presence and quantity of the desired mutant protein present in the cell.
Example 7: Growth of Genetically Modified Corynebacterium glutamicum Media and Culture Conditions Genetically modified Corynehacteria are cultured in synthetic or natural growth media. A number of different growth media for Corynebacteria are both well-known and readily available (Lieb et al. (1989) Appl. Microbiol. Biotechnol., 32:205-210; von der Osten et al. (1998) Biotechnology Letters, 11:11-16; Patent DE 4,120,867; Liebl (1992) "The Genus Corynebacterium, in: The Procaryotes, Volume II, Balows, A. et al., eds.
Springer-Verlag). These media consist of one or more carbon sources, nitrogen sources, inorganic salts, vitamins and trace elements. Preferred carbon sources are sugars, such as mono-, di-, or polysaccharides. For example, glucose, fructose, mannose, galactose, ribose, sorbose, ribulose, lactose, maltose, sucrose, raffinose, starch or cellulose serve as very good carbon sources. It is also possible to supply sugar to the media via complex compounds such as molasses or other by-products from sugar refinement. It can also be WO 01/00804 PCT/IB00/00922 -91advantageous to supply mixtures of different carbon sources. Other possible carbon sources are alcohols and organic acids, such as methanol, ethanol, acetic acid or lactic acid. Nitrogen sources are usually organic or inorganic nitrogen compounds, or materials which contain these compounds. Exemplary nitrogen sources include ammonia gas or ammonia salts, such as NH,CI or NHOH, nitrates, urea, amino acids or complex nitrogen sources like corn steep liquor, soy bean flour, soy bean protein, yeast extract, meat extract and others.
Inorganic salt compounds which may be included in the media include the chloride-, phosphorous- or sulfate- salts of calcium, magnesium, sodium, cobalt, molybdenum, potassium, manganese, zinc, copper and iron. Chelating compounds can be added to the medium to keep the metal ions in solution. Particularly useful chelating compounds include dihydroxyphenols, like catechol or protocatechuate, or organic acids, such as citric acid. It is typical for the media to also contain other growth factors, such as vitamins or growth promoters, examples of which include biotin, riboflavin, thiamin, folic acid, nicotinic acid, pantothenate and pyridoxin. Growth factors and salts frequently originate from complex media components such as yeast extract, molasses, corn steep liquor and others. The exact composition of the media compounds depends strongly on the immediate experiment and is individually decided for each specific case. Information about media optimization is available in the textbook "Applied Microbiol. Physiology, A Practical Approach (eds. P.M. Rhodes, P.F. Stanbury, IRL Press (1997) pp. 53-73, ISBN 0 19 963577 It is also possible to select growth media from commercial suppliers, like standard 1 (Merck) or BHI (grain heart infusion, DIFCO) or others.
All medium components are sterilized, either by heat (20 minutes at 1.5 bar and 121 C) or by sterile filtration. The components can either be sterilized together or, if necessary, separately. All media components can be present at the beginning of growth, or they can optionally be added continuously or batchwise.
Culture conditions are defined separately for each experiment. The temperature should be in a range between 15'C and 45'C. The temperature can be kept constant or can be altered during the experiment. The pH of the medium should be in the range of 5 to 8.5, preferably around 7.0, and can be maintained by the addition of buffers to the media.
An exemplary buffer for this purpose is a potassium phosphate buffer. Synthetic buffers such as MOPS, HEPES, ACES and others can alternatively or simultaneously be used. It WO 01/00804 PCT/IB00/00922 -92is also possible to maintain a constant culture pH through the addition of NaOH or NHIOH during growth. If complex medium components such as yeast extract are utilized, the necessity for additional buffers may be reduced, due to the fact that many complex compounds have high buffer capacities. If a fermentor is utilized for culturing the microorganisms, the pH can also be controlled using gaseous ammonia.
The incubation time is usually in a range from several hours to several days. This time is selected in order to permit the maximal amount of product to accumulate in the broth. The disclosed growth experiments can be carried out in a variety of vessels, such as microtiter plates, glass tubes, glass flasks or glass or metal fermentors of different sizes.
For screening a large number of clones, the microorganisms should be cultured in microtiter plates, glass tubes or shake flasks, either with or without baffles. Preferably 100 ml shake flasks are used, filled with 10% (by volume) of the required growth medium. The flasks should be shaken on a rotary shaker (amplitude 25 mm) using a speed-range of 100 300 rpm. Evaporation losses can be diminished by the maintenance of a humid atmosphere; alternatively, a mathematical correction for evaporation losses should be performed.
If genetically modified clones are tested, an unmodified control clone or a control clone containing the basic plasmid without any insert should also be tested. The medium is inoculated to an OD600 of 0.5 1.5 using cells grown on agar plates, such as CM plates (10 g/l glucose, 2,5 g/l NaCI, 2 g/l urea, 10 g/l polypeptone, 5 g/l yeast extract, 5 g/l meat extract, 22 g/l NaCI, 2 g/l urea, 10 g/l polypeptone, 5 g/l yeast extract, 5 g/1 meat extract, 22 g/i agar, pH 6.8 with 2M NaOH) that had been incubated at 30'C. Inoculation of the media is accomplished by either introduction of a saline suspension of C. glutamicum cells from CM plates or addition of a liquid preculture of this bacterium.
Example 8 In vitro Analysis of the Function of Mutant Proteins The determination of activities and kinetic parameters of enzymes is well established in the art. Experiments to determine the activity of any given altered enzyme must be tailored to the specific activity of the wild-type enzyme, which is well within the ability of one of ordinary skill in the art. Overviews about enzymes in general, as well as specific details concerning structure, kinetics, principles, methods, applications and examples for the determination of many enzyme activities may be WO 01/00804 PCT/IB00/00922 -93found, for example, in the following references: Dixon, and Webb, (1979) Enzymes. Longmans: London; Fersht, (1985) Enzyme Structure and Mechanism.
Freeman: New York; Walsh, (1979) Enzymatic Reaction Mechanisms. Freeman: San Francisco; Price, Stevens, L. (1982) Fundamentals of Enzymology. Oxford Univ.
Press: Oxford; Boyer, ed. (1983) The Enzymes, 3 rd ed. Academic Press: New York; Bisswanger, (1994) Enzymkinetik, 2 nd ed. VCH: Weinheim (ISBN 3527300325); Bergmeyer, Bergmeyer, GraBI, eds. (1983-1986) Methods of Enzymatic Analysis, 3 rd ed., vol. I-XII, Verlag Chemie: Weinheim; and Ullmann's Encyclopedia of Industrial Chemistry (1987) vol. A9, "Enzymes". VCH: Weinheim, p.
352-363.
The activity of proteins which bind to DNA can be measured by several wellestablished methods, such as DNA band-shift assays (also called gel retardation assays).
The effect of such proteins on the expression of other molecules can be measured using reporter gene assays (such as that described in Kolmar, H. et al. (1995) EMBO J. 14: 3895-3904 and references cited therein). Reporter gene test systems are well known and established for applications in both pro- and eukaryotic cells, using enzymes such as beta-galactosidase, green fluorescent protein, and several others.
The determination of activity of membrane-transport proteins can be performed according to techniques such as those described in Gennis, R.B. (1989) "Pores, Channels and Transporters", in Biomembranes, Molecular Structure and Function, Springer: Heidelberg, p. 85-137; 199-234; and 270-322.
Example 9: Analysis of Impact of Mutant Protein on the Production of the Desired Product The effect of the genetic modification in C. glutamicum on production of a desired compound (such as an amino acid) can be assessed by growing the modified microorganism under suitable conditions (such as those described above) and analyzing the medium and/or the cellular component for increased production of the desired product an amino acid). Such analysis techniques are well known to one of ordinary skill in the art, and include spectroscopy, thin layer chromatography, staining methods of various kinds, enzymatic and microbiological methods, and analytical chromatography such as high performance liquid chromatography (see, for example, WO 01/00804 PCT/IB00/00922 -94- Ullman, Encyclopedia of Industrial Chemistry, vol. A2, p. 89-90 and p. 443-613, VCH: Weinheim (1985); Fallon, A. et al, (1987) "Applications of HPLC in Biochemistry" in: Laboratory Techniques in Biochemistry and Molecular Biology, vol. 17; Rehm et al.
(1993) Biotechnology, vol. 3, Chapter III: "Product recovery and purification", page 469-714, VCH: Weinheim; Belter, P.A. et al. (1988) Bioseparations: downstream processing for biotechnology, John Wiley and Sons; Kennedy, J.F. and Cabral, J.M.S.
(1992) Recovery processes for biological materials, John Wiley and Sons; Shaeiwitz, J.A. and Henry, J.D. (1988) Biochemical separations, in: Ulmann's Encyclopedia of Industrial Chemistry, vol. B3, Chapter 11, page 1-27, VCH: Weinheim; and Dechow, F.J. (1989) Separation and purification techniques in biotechnology, Noyes Publications.) In addition to the measurement of the final product of fermentation, it is also possible to analyze other components of the metabolic pathways utilized for the production of the desired compound, such as intermediates and side-products, to determine the overall yield, production, and/or efficiency of production of the compound. Analysis methods include measurements of nutrient levels in the medium sugars, hydrocarbons, nitrogen sources, phosphate, and other ions), measurements of biomass composition and growth, analysis of the production of common metabolites of biosynthetic pathways, and measurement of gasses produced during fermentation.
Standard methods for these measurements are outlined in Applied Microbial Physiology, A Practical Approach, P.M. Rhodes and P.F. Stanbury, eds., IRL Press, p. 103-129; 131- 163; and 165-192 (ISBN: 0199635773) and references cited therein.
Example 10: Purification of the Desired Product from C. glutamicum Culture Recovery of the desired product from the C. glutamicum cells or supernatant of the above-described culture can be performed by various methods well known in the art.
If the desired product is not secreted from the cells, the cells can be harvested from the culture by low-speed centrifugation, the cells can be lysed by standard techniques, such as mechanical force or sonication. The cellular debris is removed by centrifugation, and the supematant fraction containing the soluble proteins is retained for further purification of the desired compound. If the product is secreted from the C glutamicum WO 01/00804 PCT/IB00/00922 cells, then the cells are removed from the culture by low-speed centrifugation, and the supemate fraction is retained for further purification.
The supernatant fraction from either purification method is subjected to chromatography with a suitable resin, in which the desired molecule is either retained on a chromatography resin while many of the impurities in the sample are not, or where the impurities are retained by the resin while the sample is not. Such chromatography steps may be repeated as necessary, using the same or different chromatography resins. One of ordinary skill in the art would be well-versed in the selection of appropriate chromatography resins and in their most efficacious application for a particular molecule to be purified. The purified product may be concentrated by filtration or ultrafiltration, and stored at a temperature at which the stability of the product is maximized.
There are a wide array of purification methods known to the art and the preceding method of purification is not meant to be limiting. Such purification techniques are described, for example, in Bailey, J.E. Ollis, D.F. Biochemical Engineering Fundamentals, McGraw-Hill: New York (1986).
The identity and purity of the isolated compounds may be assessed by techniques standard in the art. These include high-performance liquid chromatography (HPLC), spectroscopic methods, staining methods, thin layer chromatography, NIRS, enzymatic assay, or microbiologically. Such analysis methods are reviewed in: Patek et al. (1994) Appl. Environ. Microbiol. 60: 133-140; Malakhova et al. (1996) Biotekhnologiya 11: 27- 32; and Schmidt et al. (1998) Bioprocess Engineer. 19: 67-70. Ulmann's Encyclopedia of Industrial Chemistry, (1996) vol. A27, VCH: Weinheim, p. 89-90, p. 521-540, p. 540- 547, p. 559-566, 575-581 and p. 581-587; Michal, G. (1999) Biochemical Pathways: An Atlas of Biochemistry and Molecular Biology, John Wiley and Sons; Fallon, A. et al.
(1987) Applications of HPLC in Biochemistry in: Laboratory Techniques in Biochemistry and Molecular Biology, vol. 17.
EXAMPLE 11: Cloning of a Corynebacterium glutamicum Gene Involved in Lincomycin Resistance Using a Reporter Gene Approach A. Identification ofthe Gene Encoding the LMRB Protein WO 01/00804 PCT/IB00/00922 -96- Plasmid pSL 130 was constructed by ligation of the aceB promoter region (paceB) of C. glutamicum (Kim, H.J. et al. (1997) J. Microbiol. Biotechnol. 7: 287-292) into the polylinker of the lac operon fusion vector pRS415, which lacks a promoter (Simon, R.W. et al. (1987) Gene 53: 85-96). Plasmid pSL145 was constructed by ligating the resulting paceB-lac region into the E. coli cloning vector pACYC 184. E.
coli DH5aF' was transformed with pSL145 and the resulting strain was used as a host for screening of a genomic C glutamicum library (in pSL109).
Transformants were screened by growth on agar medium containing 5-bromo-4chloro-3-indolyl-beta-D-glalactopyranoside (X-Gal). A white colony, containing DNA influencing lacZ expression, was selected for further analysis. This clone was found to contain a 4 kB fragment from the gene library. Subclones were constructed in pSL109 and a subclone which retained the white phenotype on X-Gal plates was identified. This subclone was found to contain a 2.6 kB BamHI-XhoI fragment (plasmid pSL149-5).
The fragment was sequenced and identified as a membrane protein-encoding gene (LMRB gene).
The 1442 nucleotides of the coding sequence of the LMRB gene encode a polypeptide of 481 amino acid residues with a high percentage of hydrophobic amino acids. A Genbank search determined that the LMRB protein is 40% identical to the protein product of the ImrB gene from Bacillus subtilis (Genbank Accession AL009126, TREMBL Accession P94422), as determined using a CLUSTAL W analysis (using standard parameters).
The LMRN protein contains a sequence pattern: 158-A-P-A-L-G-P-T-L-S-G-167 (SEQ ID NO:301), which resembles the known multi-drug-resistance-protein consensus motif G-X-X-X-G-P-X-X-G-G (SEQ ID NO:302) (Paulsen, and Skurray, R.A.
(1993) Gene 124: 1-11). Therefore, the LMRB protein was classified as a drug resistance protein.
B. In vivo Analysis of lmrB Function The ImrB gene was overexpressed in C. glutamicum ASO19E12 (Kim, H.J. et al.
(1997) J. Microbiol. Biotechnol. 7: 287-292) using the plasmid pSL149-5, described above.
WO 01/00804 PCT/IB00/00922 -97- Disruption of the LMRB gene was accomplished by use of the vector pSL 18- ImrB. This vector was constructed as follows: an internal fragment of the LMRB gene was amplified by PCR under standard conditions using primers CTCCAGGATTGCTCCGAAGG-3' (SEQ ID NO:303) and CACAGTGGTTGACCACTGGC-3' (SEQ ID NO:304). The resulting PCR product was treated with T7 DNA polymerase and T7 polynucleotide kinase, and was cloned into the Smal site of plasmid pSL18 (Kim, Y.H. and Lee (1996) J. Microbiol.
Biotechnol. 6: 315-320). The disruption of the LMRB gene in C. glutamicum AS019E2 was performed by conjugation, as previously described (Schwarzer and Puhler (1991) Bio/Technology 9:84-87).
C. glutamicum cells transformed with pSL 149-5 displayed similar resistances as untransformed cells against erythromycin, penicillin G, tetracycline, chloramphenicol, spectinomycin, nalidixic acid, gentamycin, streptomycin, ethidium bromide, carbonyl cyanide m-chlorophenylhydrazone (CCCP), and sodium dodecyl sulfate. Significant differences were observed, however, in the resistance of transformed and untransformed cells to lincomycin.
LMRB-overexpressing C glutamicum cells were found to be able to grow in the presence of 20 pg/ml lincomycin. In contrast, cells which do not overexpress LMRB (or cells carrying a LMRB disruption) were not able to grow on agar media containing ig/ml lincomycin. This effect was clearly visible in liquid culture. LMRB overexpression led to a 9-fold increased resistance (compared to wild-type) against lincomycin and LMRB disruption resulted in a decreased resistance (28% of wild-type) to this antibiotic.
Example 12: Analysis of the Gene Sequences of the Invention The comparison of sequences and determination of percent homology between two sequences are art-known techniques, and can be accomplished using a mathematical algorithm, such as the algorithm of Karlin and Altschul (1990) Proc. Natl. Acad. Sci.
USA 87:2264-68, modified as in Karlin and Altschul (1993) Proc. Natl. Acad Sci. USA 90:5873-77. Such an algorithm is incorporated into the NBLAST and XBLAST programs (version 2.0) of Altschul, et al. (1990) J. Mol. Biol. 215:403-10. BLAST nucleotide searches can be performed with the NBLAST program, score 100, WO 01/00804 PCT/IB00/00922 -98wordlength 12 to obtain nucleotide sequences homologous to SRT nucleic acid molecules of the invention. BLAST protein searches can be performed with the XBLAST program, score 50, wordlength 3 to obtain amino acid sequences homologous to SRT protein molecules of the invention. To obtain gapped alignments for comparison purposes, Gapped BLAST can be utilized as described in Altschul et al., (1997) Nucleic Acids Res. 25(17):3389-3402. When utilizing BLAST and Gapped BLAST programs, one of ordinary skill in the art will know how to optimize the parameters of the program XBLAST and NBLAST) for the specific sequence being analyzed.
Another example of a mathematical algorithm utilized for the comparison of sequences is the algorithm of Meyers and Miller ((1988) Comput. Appl. Biosci. 4: 11- 17). Such an algorithm is incorporated into the ALIGN program (version 2.0) which is part of the GCG sequence alignment software package. When utilizing the ALIGN program for comparing amino acid sequences, a PAM120 weight residue table, a gap length penalty of 12, and a gap penalty of 4 can be used. Additional algorithms for sequence analysis are known in the art, and include ADVANCE and ADAM. described in Torelli and Robotti (1994) Comput. Appl. Biosci. 10:3-5; and FASTA, described in Pearson and Lipman (1988) P.N.A.S. 85:2444-8.
The percent homology between two amino acid sequences can also be accomplished using the GAP program in the GCG software package (available at http://www.gcg.com), using either a Blosum 62 matrix or a PAM250 matrix, and a gap weight of 12, 10, 8, 6, or 4 and a length weight of 2, 3, or 4. The percent homology between two nucleic acid sequences can be accomplished using the GAP program in the GCG software package, using standard parameters, such as a gap weight of 50 and a length weight of 3.
A comparative analysis of the gene sequences of the invention with those present in Genbank has been performed using techniques known in the art (see, Bexevanis and Ouellette, eds. (1998) Bioinformatics: A Practical Guide to the Analysis of Genes and Proteins. John Wiley and Sons: New York). The gene sequences of the invention were compared to genes present in Genbank in a three-step process. In a first step, a BLASTN analysis a local alignment analysis) was performed for each of the sequences of the invention against the nucleotide sequences present in Genbank, and the WO 01/00804 PCT/IB00/00922 -99top 500 hits were retained for further analysis. A subsequent FASTA search a combined local and global alignment analysis, in which limited regions of the sequences are aligned) was performed on these 500 hits. Each gene sequence of the invention was subsequently globally aligned to each of the top three FASTA hits, using the GAP program in the GCG software package (using standard parameters). In order to obtain correct results, the length of the sequences extracted from Genbank were adjusted to the length of the query sequences by methods well-known in the art. The results of this analysis are set forth in Table 4. The resulting data is identical to that which would have been obtained had a GAP (global) analysis alone been performed on each of the genes of the invention in comparison with each of the references in Genbank, but required significantly reduced computational time as compared to such a database-wide GAP (global) analysis. Sequences of the invention for which no alignments above the cutoff values were obtained are indicated on Table 4 by the absence of alignment information.
It will further be understood by one of ordinary skill in the art that the GAP alignment homology percentages set forth in Table 4 under the heading homology (GAP)" are listed in the European numerical format, wherein a represents a decimal point. For example, a value of "40,345" in this column represents "40.345%".
Example 13: Construction and Operation of DNA Microarrays The sequences of the invention may additionally be used in the construction and application of DNA microarrays (the design, methodology, and uses of DNA arrays are well known in the art, and are described, for example, in Schena, M. et al. (1995) Science 270: 467-470; Wodicka, L. et al. (1997) Nature Biotechnology 15: 1359-1367; DeSaizieu, A. et al. (1998) Nature Biotechnology 16: 45-48; and DeRisi, J.L. et al.
(1997) Science 278: 680-686).
DNA microarrays are solid or flexible supports consisting of nitrocellulose, nylon, glass, silicone, or other materials. Nucleic acid molecules may be attached to the surface in an ordered manner. After appropriate labeling, other nucleic acids or nucleic acid mixtures can be hybridized to the immobilized nucleic acid molecules, and the label may be used to monitor and measure the individual signal intensities of the hybridized molecules at defined regions. This methodology allows the simultaneous quantification of the relative or absolute amount of all or selected nucleic acids in the applied nucleic WO 01/00804 PCT/IB00/00922 -100acid sample or mixture. DNA microarrays, therefore, permit an analysis of the expression of multiple (as many as 6800 or more) nucleic acids in parallel (see, e.g., Schena, M. (1996) BioEssays 18(5): 427-431).
The sequences of the invention may be used to design oligonucleotide primers which are able to amplify defined regions of one or more C. glutamicum genes by a nucleic acid amplification reaction such as the polymerase chain reaction. The choice and design of the 5' or 3' oligonucleotide primers or of appropriate linkers allows the covalent attachment of the resulting PCR products to the surface of a support medium described above (and also described, for example, Schena, M. et al. (1995) Science 270: 467-470).
Nucleic acid microarrays may also be constructed by in situ oligonucleotide synthesis as described by Wodicka, L. et al. (1997) Nature Biotechnology 15: 1359- 1367. By photolithographic methods, precisely defined regions of the matrix are exposed to light. Protective groups which are photolabile are thereby activated and undergo nucleotide addition, whereas regions that are masked from light do not undergo any modification. Subsequent cycles of protection and light activation permit the synthesis of different oligonucleotides at defined positions. Small, defined regions of the genes of the invention may be synthesized on microarrays by solid phase oligonucleotide synthesis.
The nucleic acid molecules of the invention present in a sample or mixture of nucleotides may be hybridized to the microarrays. These nucleic acid molecules can be labeled according to standard methods. In brief, nucleic acid molecules mRNA molecules or DNA molecules) are labeled by the incorporation of isotopically or fluorescently labeled nucleotides, during reverse transcription or DNA synthesis.
Hybridization of labeled nucleic acids to microarrays is described in Schena, M. et al. (1995) supra; Wodicka, L. et al. (1997), supra; and DeSaizieu A. et al. (1998), supra). The detection and quantification of the hybridized molecule are tailored to the specific incorporated label. Radioactive labels can be detected, for example, as described in Schena, M. et al. (1995) supra) and fluorescent labels may be detected, for example, by the method of Shalon et al. (1996) Genome Research 6: 639-645).
The application of the sequences of the invention to DNA microarray technology, as described above, permits comparative analyses of different strains of C.
WO 01/00804 PCT/IB00/00922 101 glutamicum or other Corynebacteria. For example, studies of inter-strain variations based on individual transcript profiles and the identification of genes that are important for specific and/or desired strain properties such as pathogenicity, productivity and stress tolerance are facilitated by nucleic acid array methodologies. Also, comparisons of the profile of expression of genes of the invention during the course of a fermentation reaction are possible using nucleic acid array technology.
Example 14: Analysis of the Dynamics of Cellular Protein Populations (Proteomics) The genes, compositions, and methods of the invention may be applied to study the interactions and dynamics of populations of proteins, termed 'proteomics'. Protein populations of interest include, but are not limited to, the total protein population of C.
glutamicum in comparison with the protein populations of other organisms), those proteins which are active under specific environmental or metabolic conditions during fermentation, at high or low temperature, or at high or low pH), or those proteins which are active during specific phases of growth and development.
Protein populations can be analyzed by various well-known techniques, such as gel electrophoresis. Cellular proteins may be obtained, for example, by lysis or extraction, and may be separated from one another using a variety ofelectrophorctic techniques. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) separates proteins largely on the basis of their molecular weight. Isoelectric focusing polyacrylamide gel electrophoresis (IEF-PAGE) separates proteins by their isoelectric point (which reflects not only the amino acid sequence but also posttranslational modifications of the protein). Another, more preferred method of protein analysis is the consecutive combination of both IEF-PAGE and SDS-PAGE, known as 2-D-gel electrophoresis (described, for example, in Hermann et al. (1998) Electrophoresis 19: 3217-3221; Fountoulakis et al. (1998) Electrophoresis 19: 1193-1202; Langen et al.
(1997) Electrophoresis 18: 1184-1192; Antelmann etal. (1997) Electrophoresis 18: 1451-1463). Other separation techniques may also be utilized for protein separation, such as capillary gel electrophoresis; such techniques are well known in the art.
Proteins separated by these methodologies can be visualized by standard techniques, such as by staining or labeling. Suitable stains are known in the art, and WO 01/00804 PCT/IB00/00922 102include Coomassie Brilliant Blue, silver stain, or fluorescent dyes such as Sypro Ruby (Molecular Probes). The inclusion of radioactively labeled amino acids or other protein precursors 3SS-methionine, 3 S-cysteine, 4 C-labelled amino acids, 'IN-amino acids, 'sNO 3 or 5 NH4 or 3 C-labelled amino acids) in the medium of C. glutamicum permits the labeling of proteins from these cells prior to their separation. Similarly, fluorescent labels may be employed. These labeled proteins can be extracted, isolated and separated according to the previously described techniques.
Proteins visualized by these techniques can be further analyzed by measuring the amount of dye or label used. The amount of a given protein can be determined quantitatively using, for example, optical methods and can be compared to the amount of other proteins in the same gel or in other gels. Comparisons of proteins on gels can be made, for example, by optical comparison, by spectroscopy, by image scanning and analysis of gels, or through the use of photographic films and screens. Such techniques are well-known in the art.
To determine the identity of any given protein, direct sequencing or other standard techniques may be employed. For example, N- and/or C-terminal amino acid sequencing (such as Edman degradation) may be used, as may mass spectrometry (in particular MALDI or ESI techniques (see, Langen et al. (1997) Electrophoresis 18: 1184-1192)). The protein sequences provided herein can be used for the identification of C. glutamicum proteins by these techniques.
The information obtained by these methods can be used to compare patterns of protein presence, activity, or modification between different samples from various biological conditions different organisms, time points of fermentation, media conditions, or different biotopes, among others). Data obtained from such experiments alone, or in combination with other techniques, can be used for various applications, such as to compare the behavior of various organisms in a given metabolic) situation, to increase the productivity of strains which produce fine chemicals or to increase the efficiency of the production of fine chemicals.
05/10 '05 WED 13:11 FAX 61 2 9888 7600 WATERMARK 3012 103
EQUIVALENTS
Those of ordinary skill in the art will recognize, or will be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following claims.
Comprises/comprising and grammatical variations thereof when used in this specification are to be taken to specify the presence of stated features, integers, steps or components or groups thereof, but do not preclude the presence or addition of one or more other features, integers, steps, components or groups thereof.
S COMS ID No: SBMI-01664086 Received by IP Australia: Time 13:19 Date 2005-10-05 EDITORIAL NOTE APPLICATION NUMBER 58369/00 The following Sequence Listing pages 1 to 416 are part of the description. The claims pages follow on pages "104" to "108".
wo 01/00804 WO 0100804PCT/I B00100922 SEQUENCE LISTING <110> BASF Aktiengesellschaft <120> CORYNEBACTERIUM GLUTAMICUM GENES ENCODING STRESS, RESISTANCE AND TOLERANCE PROTEINS <130> BGI-124CPPC <140> (141> (160> 304 <210> 1 <211> 1566 <212> DNA <213> Corynebacterium giutamicum <220> <221> COS <222> (1543) <223> RXA01524 (400> 1 ttgtggcact ctttagtagt tttttctcat agctcagttt cgcaacttta gagaactcta gaaactgagc ttcatgctgt gaaaggcctt ttctccattc atg gat Met Asp aat act Asn Thr gtt gtt Val. Val gaa acc Giu Thr gtg cct Val Pro atq gca Met Ala act aag Thr Lys ttg act Leu Thr ca g Gin Ct t Leu att Ile qaa Giu gtg Val a cg Thr gcg Ala acc Th r tcg Ser ctg Leu act Thr gtg Val1 atc Ile gcg Al a 105 t ct Ser atc Ile tcg Ser act Thr att Ile ttt Phe t tg Leu ccg gca Pro Ala ctc gtg Leu Val gtt gcg Vai Ala gca cag Ala Gin 60 cca act Pro Thr 75 gtt act Vai Thr gct cca Ala Pro gcg Al a tcc Se r 30 cct Pro t tg Leu ggt Gi y ttq Leu tt t Phe 110 aag Lys 15 gcg Al a t cc Ser a cc Thr tat Tyr ttg Leu 95 gcg Al a 1 cct Pro atc Ile atg Met ggc Giy ctt Leu ttt Phe ctg Leu agg Arg atg Met gaa Giu tt t Phe ga t Asp acg Thr ctt Leu tcc caa att Ser Gin Ile gag gtc gtt Giu Vai Val att ctt aat Ile Leu Asn gat ttc tcc Asp Phe Ser atg ttg acg Met Leu Thr cgt ttt tcc Arg Phe Ser gtt ggt acg Val Gly Thr 100 ggt gct cgt Giy Ala Arg l1r 115 163 211 259 307 355 403 451 499 atc gtt cag gcg gtt ggt act gcg ctg gtg atg cct ttg ctg Ilie Vai Gin Ala Val Giy Thr Aia Leu Val Met Pro Leu Leu atg acg Met Thr WO 01/00804 WO 0100804PCTIBOO/00922 gt t Val1 att Ile 150 tet Ser atg Met aaa Lys atc Ile ttc Phe 230 gte ValI etc Leu agg Arg atg Met gga Gly 310 ctc Leu ggt Giy acg Thr 135 att Ile ggt Gly ctt Leu aat As n et t Leu 215 gga Gly gt t Val 9gc Gly aac Asn etc Leu 295 gt t Va 1 cag Gin cca Pro t tg tee Ser gte Val1 ceg Pro atc Ile 200 tcg Ser gca Ala gge Gly aag Lys tte Phe 280 gga Gly act Thr ggt Gly egt Arg aeg gtg gtt cet geg gag egt cgt qgt tcg atg atg Thr Val Val ate Ile at t Ile ate Ile 185 gge Gly gt g Val ate Ile gee Al a caa Gin 265 age Ser ace Thr gct Ala ctg Leu ceg Pro 345 gtg Val1 et t Leu 170 gtt ValI gaa Glu ttt Phe ct g Leu ate Ilie 250 gac Asp ttc Phe gte Val ttg Leu ate Ilie 330 etg Leu att Ile 155 aae Asn gt t Val1 ace Thr gee Ala gag Giu 235 gca Al a aaa Lys tee Ser atg Met gtg Val1 315 age Ser Ctg Leu Pro Ala 140 tet gtt Ser Val tct ttg Ser Leu ate get Ile Ala aag ate Lys Ile 205 ttc ggt Phe Gly 220 gge gaa Gly Glu etc etc Leu Leu gca etg Ala Leu ttg ace Leu Thr 285 gtt ttg Val Leu 300 ace ggt Thr Gly cea tte Pro Phe att ccc Ile Pro 9c Ala ace Thr ttg Leu 190 ace Tb r ggt Gi y Giy ate Ile atg Met 270 ace Thr cc a Pro ttg Leu ate Ile gga, 350 Arg ceg Pro tgg Trp 175 gt a Vali eca Pro ttg Leu ace Thr ttt Phe 255 gat Asp ate Ile ate Ile gtt Val gga Gly 335 gca Al a Arg geg Ala 160 Ca c His att Ile etg Leu gtg Val gt a Val1 240 get Ala etc Leu et t Leu tac Tyr gtt Val 320 egt Arg att Ile Giy 145 ctt Leu t gg T rp ggt Gly gat Asp tac Tyr 225 ggt Gly ttg Leu ega Axrg t tg Leu etg Leu 305 atg Met ttc Phe geg Al a Met cct Pro ttt Phe t te Phe 195 Ct g Leu tte Phe tte Phe ca g Gln ttc Phe 275 tte Phe act Thr ggC Gly gac Asp get Al a 355 Met acg Thr tgg T rp 180 ttg Leu tet.
Ser ag t Ser geg Al a ca e His 260 aag Lys ggC Giy tee Ser qgc Gly aag Lys 340 ate Ile 9gc Gly ttg Leu 165 atg Met ate I le gte Val1 tee Se r ate Ile 245 caa Gin gtg Val geg Ala etc Leu etc Leu 325 gte Val1 geg Ala 547 595 643 691 739 787 835 883 931 979 1027 1075 1123 1171 WO 0 1/00804 WO 0100804PCT/fBOO/00922 gca tee tcg atg act ttt cte aat gag aat tca ccc gtg tgg atg gtc 1219 Ala Ser Ser Met Thr Phe Leu Asn Glu Asn Ser Pro Val Trp Met Val 360 365 370 gtg gte atg cac gtt gtg ttc age atc ggc atg tgt ttg atg atg acc 1267 Val Val Met His Val Val Phe Ser Ile Gly Met Cys Leu Met Met Thr 375 380 385 cct cte atg acc ace get etc ggc gcc ctt ccg aag cae ctc tat ggt 1315 Pro Leu Met Thr Thr Ala Leu Gly Ala Leu Pro Lys His Leu Tyr Gly 390 395 400 405 cae ggc tcc gca att ttg aac acg tte caa cag etc gca ggc gca gcc 1363 His Gly Ser Ala Ile Leu Asn Thr Phe Gin Gln Leu Ala Gly Ala Ala 410 415 420 gga aca geg ate atg att gca gca ctt tec ttc ggc act tee att gca 1411 Gly Thr Ala Ile Met Ile Ala Ala Leu Ser Phe Gly Thr Ser Ile Ala 425 430 435 geg tot tog gga tot geg cat get gaa get gtt gee get ggt ace aag 1459 Ala Ser Ser Gly Ser Ala His Ala Glu Ala Val Ala Ala Gly Thr Lys 440 445 450 gtt geg tte ate gee ggc gca ate ate geg gtg ate get ttg gtt gtt 1507 Val Ala Phe Ilie Ala Gly Ala Ile Ile Ala Val Ile Ala Leu Val Val 455 460 465 tee etc tte gte act ege gte gag gaa gee get cac taaataceaa 1553 Ser Leu Phe Val Thr Arg Val Glu Glu Glu Ala His 470 475 480 aaaatgggge aga 1566 <210> 2 <211> 481 <212> PRT <213> Corynebaeterium glutamicun <400> 2 Met Asp Ser Gin Ile Asn Thr Gin Thr Ser Pro Ala Ala Ala Lys Leu 1 5 10 Pro Arg Giu Val Val Val Val Leu Ser Ile Leu Val Val Ser Ala Met 25 Ilie Met Ilie Leu Asn Glu Thr Ile Leu Ser Val Ala Leu Pro Ser Ile 40 Met Glu Asp Phe Ser Val Pro Glu Thr Thr Ala Gin Trp Leu Thr Thr 55 Gly Phe Met Leu Thr Met Ala Val Val Ile Pro Thr Thr Gly Tyr Leu 70 75 WO 01/00804 PCT/1B00100922 Leu Asp Arg Phe Ser Thr Lys Thr Ile Phe Val Thr Ala Leu Leu Phe Phe Leu Pro Gly 145 Leu Trp Gly Asp Tyr 225 Gly Leu Arg Leu Leu 305 Met Phe Ala Thr Leu Leu 130 Ser GI y Leu Phe Val1 210 Gi y Ile Arg Ala Ala 290 Gin Pro Tyr Leu Val Gly 115 ILeu Met Pro Phe Phe 195 Leu Phe Phe Gin Phe 275 Phe Thr Gly Asp.
Ala 355 Gly 100 Ala Met Met Thr Trp 180 Leu Ser Ser Al a His 260 Lys Gly Ser Gly Lys 340 Ile Thr Arg Thr GI y Leu 165 Met Ile Val1 Se r Ile 245 Gin Val1 Ala Leu Leu 325 Val1 Ala Leu Ile Val Ile 150 Ser Met Lys Ile Phe 230 Vai Leu Arg Met Gly 310 Leu Gly Al a Thr Val Thr 135 Ile Gi y Leu Asn Leu 215 Gly Val Gly Asn Leu 295 Val Gin Pro S er Ala Gin 120 Leu Ser Val1 Pro Ile 200 Ser Al a Gi y Lys Phe 280 Gi y Thr Gly Arg Ser Ala 105 Al a Thr Ile Ile Ile 185 Gi y Val1 Ile Al a Gin 265 Ser Thr Al a Leu Pro 345 Met Leu Val1 Val Val1 Leu 170 Val1 Giu Phe Leu Ile 250 Asp Phe Val1 Leu Ile 330 Leu Thr Ala Gi y Val1 Ile 155 Asn Val Thr Al a Giu 235 Al a Lys Ser Met Val 315 Ser Leu Phe Pro Th r Pro 140 Ser Ser Ile Lys Phe 220 Gi y Leu Al a Leu Val1 300 Thr Pro Ile Leu Thr Ala 125 Ala Val Leu Ala Ile 205 Gly Glu Leu Leu Thr 285 Leu Gly Phe Pro As n 365 Phe Ala 110 Leu Val Glu Arg Ala Pro Thr Trp 175 Leu Vai 190 Thr Pro Gly Leu Gly Thr Ile Phe 255 Met Asp 270 Thr Ile Pro Ile Leu Val Ile Giy 335 Gly Ala 350 Glu Asn Val Met Arg Ala 160 His Ile Leu Val1 Val1 240 Ala Leu Leu Tyr Val1 320 Arg Ile Ser 360 Pro Val Trp Met Val Val Val Met His Val Val Phe Ser Ile Gly Met WO 01/00804 Leu Met Met His Leu Tyr Ala Gly Ala 420 Thr Ser Ile 435 Ala Gly Thr 450 Ala Leu Val PCT/IBOO/00922 <210> 3 <211> 371 <212> DNA <213> Corynebacterium glutamicum <220> <222> CDS <222> (348) <223> RXA00497 <400> 3 tggaaaccca caaccggcac acacaaaatt tttctcatgg aac Asn gag Glu a ag Lys gac Asp atc Ile ct t Leu gct Ala gca Ala cgc Arg t ac Tyr agggattcac cgtg Val1 1 ctc gtt cag atc Leu Val Gin Ile att cca gat tc Ile Pro Asp Ser gtt ggc cca ggc Val Gly Pro Gly atc aag gaa gat Ile Lys Glu Asp atc aag ttc ggt Ile Lys Phe Gly WO 01/00804 PCT/IBOO/00922 gtg gag tac ttg ctt etc tcc gct cgt gac atc etc gca atc gtc gag 345 Val Giu Tyr Leu Lou Leu Ser Ala Arg Asp Ile Leu Ala Ile Val Glu 90 aag taggggataa gttcatggca aag 371 Lys <210> 4 <211> 99 <212> PRT <213> Corynebacteriun glutamicum <400> 4 Val Ala Asn Val Asn Ilie Lys Pro Leu Glu Asp Lys Ile Leu Val Gin 1 5 10 Ile Asn Giu Ala Glu Thr Thr Thr Ala Ser Gly Leu Val Ile Pro Asp 25 Ser Ala Lys Giu Lys Pro Gin Glu Ala Thr Val Ile Ala Val Gly Pro 40 Gly Arg Phe Asp Asp Lys Gly Asn Arg Ile Pro Leu Asp Ile Lys Giu 55 Asp Asp Val Val Ile Phe Ser Arg Tyr Giy Gly Thr Giu Ile Lys Phe 70 75 Gly Gly Val Giu Tyr Leu Leu Leu Ser Ala Arg Asp Ile Leu Ala Ile 90 Val Giu Lys <210> <211> 1737 <212> DNA <213> Corynebacterium glutarnicum <220> <221> CDS <222> (1714) <223> RXN00493 <400> cccgttacgg cggcaccgag atcaagttcg gtggcgtgga. gtaettgctt etcteegetc gtgacatcct cgcaatcgtc gagaagtagg ggataagttc atg gea. aag etc att 115 Met Ala Lys Leu Ile 1 get ttt gac cag gac gcc cgc gaa ggc att etc egg ggc gtt gac get 163 Ala Phe Asp Gin Asp Ala Arg Glu Giy Ile Leu Arg Gly Val Asp Ala 15 WO 01/00804 WO 0100804PCT/IBOO/00922 ctg gca aac gct gtc aag gta acc ctc ggc Lys Val Thr Leu Gly Leu gtt Val acc Thr gcg Al a gac Asp gg C Gly ggt 91 y gca Ala tca Ser 150 aag Lys gag Glu ctt Leu gac Asp Al a ctt.
Leu att Ile cag Giln Gly ctg Leu att I le acc Thr 135 t cc Se r gtt Val act Thr tcc Se r aac Asn 215 As n gat Asp 40 gcc Al a ct g Leu acc Thr cgc Arg t ct Ser 120 gag Glu cgc Arg ggc Gly gct Ala cct Pro 200 cct Pro Al a aag Lys cgc Arg gt g Val a cg Thr aac As n 105 gca Ala gtg Val1 gat Asp aag Lys ctc Leu 185 tat Tyr gca Ala Val gca Ala gac Asp aaq Lys act Th r gt t Val1 gct Al a t ct Ser gaa Glu ga c Asp 170 gag Glu t tc Phe gtg Val1 cca cgc ggc cgt aac gtg Pro Arg Gly Arg Asn Val ttc Phe atc Ile tcc Ser 75 gca Ala gct Ala gca Ala ga c Asp gt t Val1 155 gg t Gly gtc Val1 atc I le ctg Leu ggc Gly ga c Asp 60 gtt Val1 act Thr gct Ala gaa Giu acc Th r 140 gtc Val1 gtC Val acc Thr aac Asn ctt Leu 220 gga Gly 45 ctt Leu gct Ala ctg Leu ggc Gly aag Lys 125 aag Lys ggc Gly gtc Val1 gaa Glu ga c Asp 205 gt t ValI cct Pro gag Glu gt t Val1 ct t Leu gc a Al a 110 acc Thr qaa Glu gag Glu a cc Thr ggt.
Gly 190 aac Asn cgc Arg ct g Leu ga t Asp aag Lys gct Al a 95 aac Asn t tg Leu atc Ile atc Ile gt t Val1 175 att Ile gac Asp aac As n gtc Val cct Pro a cc Thr 80 cag Gin cca Pro gaa Giu gca Al a gtt ValI 160 gag Glu tct Ser act Thr aa g Lys acc Thr ttt Phe aa c As n gca Ala atg Met gag Giu aac Asn 145 gct.
Ala gag Glu ttc Phe cag Gin at t Ile 225 aac gac Asn Asp gag aac Giu Asn gac atc Asp Ile ctc att Leu Ile gag ctc Giu Leu 115 ttq aag Leu Lys 130 gtc gct Val Ala gca gcg Ala Ala tcc cag Ser Gin gac aag Asp Lys 195 cag gct Gln Ala 210 tct tcc Ser Ser ggt gtC Gly Val ctc ggt Leu Gly gct ggt Ala Gly gct gaa Ala Giu 100 aac aag Asn Lys gca cgc Ala Arg acc gtt Thr Val atg gaa Net Glu 165 tcc atc Ser Ile 180 ggc tac Gly Tyr gtc ctg Val Leu ctc cca Leu Pro 211 259 307 355 403 451 499 547 595 643 691 739 787 gac ttc ctc cca ttg ctg gag aag Asp Phe Leu Pro Leu Leu Glu Lys 230 235 gtt gtg gag Val Val Giu 240 tcc aac cgt cct ttg Ser Asn Arg Pro Leu 245 WO 01/00804 ctg atc ate gca gaa gac gtc gag ggc gag cct ttg cag acc ctg gtt Leu Ile Ile Ala Glu Asp Val Glu Gly Glu Pro Leu Gin Thr Leu Vai PCT/IBOO/00922 250 260 gtg Val tac Tyr ace Thr gct Ala 310 ga c Asp gca Ala tgg Trp att .le cgc Arg 390 caa Gin gag Glu ggc Gly1 gccI aac Asn ttc Phe aag Lys 295 ggc Gly gaa Glu cgt Arg gat Asp gct Ala 375 aag L.ys gaa Glu act rhr gtt Val tee tee Ser ggt Gly 280 gca Ala gaa Giu acc Thr cgc Arg cgc- Arg 360 gtc ValI ctg Leu 9gc Gly ctg Leu cgc Arg 440 aa c atc Il 26! gac AsF act Thr g aa Glu ate Ile Gi y 345 ga a Gi u ate Ile cgt Arg gtt Val1 aag Lys 425 gca Ala gca -cgc SArg -cga Arg gtc Val gtt IVal ate Ile 330 cag Gin aag Lys cgc Arg gtc Val atc Ile 410 gct Ala ctg c Leu ggt c aac Lys cgc Arg gtg ValI t tc Phe 315 gt Val1 ate Ile gca Ala gt t Val gaa 395 get tac ryr ;ct la :tt acc atc *Thr Ile *aag gcg Lys Ala 285 gat cca Asp Pro 300 ggt acc Gly Thr gat ggt Asp Gly cgt cgc Arg Arg gaa gag Giu Glu 365 ggt gca Gly Ala 380 gat gcc Asp Aia ggt ggc Gly Gly gcc qaa Ala Glu act gct1 Thr Ala 445 gac ggcI Asp Gly 1 460 aag Lys 270 ttc Phe gaa Giu gca Al a gca Al1 a gaa Glu 350 cgt Arg gca Ala atc Ile ggt Gly gag .,lu 430 ttg Leu :ct e r gtc ValI at g Met gt g Val1 cgc Arg ggt Gly 335 ate Ile ttg Leu act Thr aac Asn tee Ser 415 ttc Phe ggc Gly gtt Val gt t Val1 gat Asp ggC Gly cgc Arg 320 tcc Ser gcc Ala gct Al a gaa Giu gct Ala 400 get Ala gaa Glu aag Lys gt t lal gca Ala gac Asp ate Ile 305 ate Ile gca Ala aac As n aag Lys ace Thr 385 gct Ala ttg Leu ggc GI y cca Pro gtt Val 465 gtg Val ctg Leu 290 aac Asn ace Th r gaa Glu acc Thr ctc Leu 370 gaa Glu cgc Arg gt t ValI gac Asp gcg Ala 450 gca Ala aag Lys 275 get Al a ct c Leu gt t Val1 gac Asp gat Asp 355 tee Ser gtc Val gca Al a cag, Gln cag Gln 435 tac Tyr :gc Irg tcc Ser att Ile aac Asn teec Ser gtt Val1 340 tec Ser ggt GI y aac Asn gca Ala ate Ile 420 aag Lys t gg Trp act Thr cct Pro gtc Val1 ga a Glu aa g Lys 325 ga a Glu ace Thr ggt Gly gac Asp gca Ala 405 gct Ala gtc Val1 ate Ile gct Ala 931 979 1027 1075 1123 1171 1219 1267 1315 1363 1411 1459 1507 1555 Ala Ser Asn Ala Gly Leu 455 gct ctg cca aac ggc gag ggc ttc aac gct gca act ttg gaa tac gga WO 01/00804 Ala Leu Pro Asn Gly Glu Gly Phe Asn Ala Ala Thr Leu Glu Tyr Gly 470 475 480 485 aac ctg atc aac gac ggt gtc atc gac cca gtc aag gtc acc cat tcc Asn Leu Ile Asn Asp Gly Val Ile Asp Pro Val Lys Val Thr His Ser 490 495 500 gca gta gtg aat gca acc tct gtt gca cgc atg gtt ctg acc act gag Ala Val Val Asn Ala Thr Ser Val Ala Arg Met Val Leu Thr Thr Glu 505 510 515 gct tct gtt gtt gag aag cct gca gaa gaa gca gcc gat gca cat qca Ala Ser Val Val Glu Lys Pro Ala Glu Glu Ala Ala Asp Ala His Ala 520 525 530 gga cat cat cac cac taaagttctg tgaaaaacac cgt Gly His His His His 535 <210> 6 <211> 538 <212> PRT <213> Corynebacteriun glutanicun <400> 6 Met Ala Lys Leu Ile Ala Phe Asp Gln Asp Ala Arg Glu Gly Ile Leu PCT/IBOO/00922 1603 1651 1699 1737 1 Arg Arg Thr Phe Asn Ala Met Glu Asn 145 Gly Gly Asn Glu Asp Leu Glu Leu 130 Val Al a Val1 Val1 Gly City Glu Lys Arg Val1 Leu Val1 Thr Al a Asp Gly Gi y Al a Ser Al a Leu Ilie Gin Gly Leu Ilie Thr 135 Ser Asn Asp Ala Leu Thr Arg Se r 120 Glu Arg 150 155 Ala Ala Ala Met Glu Lys Val Gly Lys Asp Gly Val Val Thr Val Glu WO 01/00804 PCT/IBOO/00922 165 170 175 Glu Ser Gin Ser Ilie Giu Thr Ala Leu Glu Val Thr Giu Gly Ile Ser 180 185 190 Phe Asp Lys Gly Tyr Leu Ser Pro Tyr Phe Ile Asn Asp Asn Asp Thr 195 200 205 Gin Gin Ala Val Leu Asp Asn Pro Ala Val Leu Leu Val Arg Asn Lys 210 215 220 Ilie Ser Ser Leu Pro Asp Phe Leu Pro Leu Leu Giu Lys Val Val Glu 225 230 235 240 Ser Asn Arg Pro Leu Leu Ile Ile Ala Giu Asp Val Glu Gly Giu Pro 245 250 255 Leu Gin Thr Leu Val Val Asn Ser Ile Arg Lys Thr Ile Lys Val Val 260 265 270 Ala Val Lys Ser Pro Tyr Phe Gly Asp Arg Arg Lys Ala Phe Met Asp 275 280 285 Asp Leu Ala Ile Val Thr Lys Ala Thr Val Val Asp Pro Giu Val Gly 290 295 300 Ile Asn Leu Asn Giu Ala Gly Clu Giu Val Phe Gly Thr Ala Arg Arg 305 310 315 320 Ile Thr Val Ser Lys Asp Glu Thr Ilie Ilie Val Asp Gly Ala Gly Ser 325 330 335 Ala Giu Asp Val Giu Ala Arg Arg Gly Gin Ile Arg Arg Glu Ile Ala 340 345 350 Asn Thr Asp Ser Thr Trp, Asp Arg Glu Lys Ala Giu Giu Arg Leu Ala 355 360 365 Lys Leu Ser Gly Gly Ile Ala Val Ilie Arg Val Gly Ala Ala Thr Glu 370 375 380 Thr Glu Val Asn Asp Arg Lys Leu Arg Val Giu Asp A-la Ile Asn Ala 385 390 395 400 Ala Arg Ala Ala Ala Gin Giu Gly Vai Ile Ala Gly Gly Gly Ser Ala 405 410 415 Leu Val Gin Ile Ala Giu Thr Leu Lys Ala Tyr Ala Giu Giu Phe Glu 420 425 430 Gly Asp Gin Lys Val Gly Val Arg Ala Leu Ala Thr Ala Leu Gly Lys 435 440 445 Pro Ala Tyr Trp Ilie Ala Ser Asn Ala Gly Leu Asp Gly Ser Val Val 450 455 460 Val Ala Arg Thr Ala Ala Leu Pro Asn Gly Giu Gly Phe Asn Ala Ala WO 01/00804 465 470 475 480 Thr Leu Glu Tyr Gly Asn Leu Ile Asn Asp Gly Val Ile Asp Pro Val 485 490 495 Lys Val Thr His Ser Ala Val Val Asn Ala Thr Ser Val Ala Arg Met 500 505 510 Val Leu Thr Thr Glu Ala Ser Val Val Glu Lys Pro Ala Glu Glu Ala 515 520 525 Ala Asp Ala His Ala Gly His His His His 530 535 <210> 7 <211> 1339 <212> DNA 'z213> Corynebacterium glutamicum <220> <221> CDS <222> (101)..(C1339) <223> FRXA00498 <400> 7 cccgttacgg cggcaccgag atcaagttcg gtggcgtgga gtacttgctt ctctccgct gtgacatcct cgcaatcgtc gagaagtagg ggataagttc atg gca. aag ctc att Met Ala Lys Leu Ile PCT/IBOO/00922 ;c gct Ala ctg Leu gt t Val acc Thr gcg Ala gac Asp ggC ttt gac Phe Asp gca aac Ala Asn ctt gat Leo Asp att gcc Ile Ala cag cig Gin Leu ggc acc Gly Thr ctg cgc gac gcc Asp Ala gtc aag Val Lys gca ttc Ala Phe gac atc Asp Ile aag tcc Lys Ser act gca Thr Ala gtt gct cgc Arg gta Val1 99C Gly gac Asp 60 gtt Val act Thr gct ggc Gi y ct C Leu cct Pro gag Glu gt t Val1 ct t Leu gca att Ile 15 ggC Gly ctg Leu gat Asp aag Lys gct Ala 95 aac 1 cgg Arg cgc Arg acc Thr ttt Phe aac Asn gca Ala atg ggc gtt Gly Val ggC cgt Gly Arg aac gac Asn Asp gag aac Glu Asn gac atc Asp Ile ctc att Leu Ile gag ctc gac Asp aac Asn ggt GI y ctc Leu gct Ala gct Ala 100 a ac WO 01/00804 WO 0100804PCTIBOO/00922 Gly ggt Gly gca Ala t ca Se r 150 aag Lys gag Giu ct t Leu gac Asp gac Asp 230 ctg Leu gt g Val1 tac Tyr aCC Thr gct Ala 310 Leu att Ile acc Th r 135 t cc Se r gtt Vai act Thr tcc Ser aac As n 215 ttc Phe atc Ile aac Asn ttc Phe a ag Lys 295 9gC 1 ly Arg tct Ser 120 gag Giu cgc Arg ggc Gly gct Ala cct Pro 200 oct Pro Ctc Leu atc Ile t cc S er ggt Gly 280 gca Ala gaa Giu Asn Val Ala Ala Gly Ala Asn Pro Met Glu Leu Asn Lys 105 gca Ala gtg Val gat Asp aag Lys Ct C Leu 185 tat Tyr gca Ala c ca Pro gca Ala atc Ilie 265 gao Asp act Thr gaa Glu gct Ala tot Ser gaa Giu ga c Asp 170 gag Glu ttc Phe gtg ValI ttg Leu gaa Glu 250 cgc Arg cga Arg gtc Val gt t Val1 110 gca Ala gac Asp Igtt Val 155 ggt Gly gt C Val atc Ile ctg Leu ctg Leu 235 ga C Asp aag Lys cgc Arg gtg Val ttc Phe 315 gaa Giu acc Thr 140 gtc Val1 g tc Val1 acc Thr aac Asn Ct t Leu 220 gag Giu gtc Val aCC Thr a ag Lys gat Asp 300 ggt aag Lys 125 aag Lys ggc Gly gtc Val1 gaa Glu gac Asp 205 gt t Val aag Lys gag Glu atc Ile gcg Ala 285 cca Pro acc Thr acc Thr gaa Gi u gag Giu acc Th r ggt Gly 190 aac Asn cgc Arg gt t Val1 ggc Gly aag Lys 270 t tc Phe gaa Glu gca Al a ttg *Leu atc Ile atc Sle gtt Val 175 att Ile gac Asp aac Asn gtg ValI gag Giu 255 gtc Val atg Met gtg Val1 cgc Arg gaa Giu gca Ala gtt Val1 160 gag Glu tct Se r act Thr aag Lys gag Glu 240 cct Pro gtt Val gat Asp ggc GI y cgc Arg 320 gag Glu aac Asn 145 gct Ala gag Glu ttc Phe cag Gin att Ile 225 tcc Ser ttg Leu gca Al a ga c Asp atc Ile 305 atc Ile ttg Leu 130 gt c Val1 gca Al a t cc Se r gac Asp cag Gin 210 t ct Ser aac Asn cag Gin gtg Val1 ctg Leu 290 aac Asn a cc Thr 115 aag gca Lys Ala gct acc Ala Thr gcg atg Ala Met cag tcc Gin Ser 180 aag ggc Lys Gly 195 gCt gto Ala Val tcc ctc Ser Leu cgt cct Arg Pro acc Ctg Thr Leu 260 aag tc Lys Ser 275 gct att Ala Ile ctc aac Leu Asn gtt tcc Val Ser cgc Arg gt t Val1 ga a Glu 165 atc Ile tac Tyr ctg Leu cca Pro t tg Leu 245 gtt Val1 cct Pro gt c Val gaa Glu aag Lys 325 499 547 595 643 691 739 787 835 883 931 979 1027 1075 1123 gac gaa acc atc atc Asp Glu Thr Ile Ilie gat ggt gca ggt tcc A-sp Gly Ala Giy Ser gca gaa gac gtt gaa Ala Giu Asp Val Glu WO 01/00804 gca Ala t gg Trp att Ilie ege Arg 390 caa Gin gcc aac acc gat Ala Asn Thr Asp 355 get aag ctc tcc Ala Lys Leu Ser 370 gaa ace gaa gte Giu Thr Giu Val 385 gct gct ege gca Ala Ala Arg Ala 400 340 tcc Ser ggt Gly aac Asn gca Ala PCT/IBOO/00922 1171 1219 1267 1315 1339 <210> 8 <211> 413 <212> PRT <213> Corynebacterium giutamicum <400> 8 Met Ala Lys Leu Ile Ala Phe Asp Gin 1 Arg Arg Thr Phe Asn Ala Met Glu Asn Gly Val Gly Arg Asn Asp Giu Asn Asp Ilie Leu Ile Giu Leu 115 Leu Lys 130 Val Ala Leu Val Thr Al a 70 Asp Gly Gly Ala Se r Al a Leu Ile Gin Gly Leu Ile Thr 135 Ser Ala Lys Arg Val Thr Asn 105 Ala Val Asp Asp Val1 Al a Asp Lys Thr ValI Ala Ser Glu Leu Pro Val Pro Thr Gin Pro Giu Al a Val1 WO 01/00804 WO 0100804PCT/IBOO/00922 Ala Glu Phe Gin Ile 225 Ser Leu Al a Asp Ile 305 Ile Ala Asn Lys Thr 385 Aia Gin Lys 195 Ala Ser Arg Thr Lys 275 Ala.
Leu Val Asp Asp 355 Ser Val Glu Lys 165 Ile Glu Tyr Leu Leu Asp Pro Asp 230 Leu Leu 245 Val Val Pro Tyr Val Thr Giu Ala 310 Lys Asp 325 Giu Ala Thr Trp Gly Ile Asp Arg 390 Giy Ala Pro 200 Pro Leu Ile Se r Gly 280 Ala Gi u Thr Arg Arg 360 Val Leu Asp Gly 170 Giu Val Phe Ilie Val Leu Leu Leu 235 Glu Asp 250 Arg Lys Arg Arg Val Val Val Phe 315 Ile Val 330 Gin Ile Lys Ala Arg Val Val Glu 395 Val1 Thr Asn Leu 220 Giu Val Thr Lys Asp 300 Gly Asp Arg Glu Gly 380 Asp Thr Gly 190 Asn Arg Val1 Gi y Lys 270 Phe Giu Ala Ala Giu 350 Arg Ala I le Ala Arg Ala Ala Gin Giu Gly Val Ala Gly Giy <210> 9 <211> 723 <212> DNA <213> Corynebacteriun giutamicum <220> WO 01/00804 <221> CDS <222> (700) <223> RXA01217 <400> 9 gcgctgcctg cgaagactcg accaagacat tegagtcggt PCTIBOO/00922 cgcgggcatt ttttattttc gcggccgagt gtccaccttc atccatgagg agaaatcact atg gca aag tac caa Met Ala Lys Tyr Gin ace Thr cgt Arg gt t Val1 ct g Leu ggc Gly ace Thr aag Lys gge Gly gtt Val etc Leu 150 ace Thr gag Glu cgc Axg tee Ser cge Arg aag Lys cac His gag Giu atg Met 120 t cc Ser gca Ala gtt Val gct Ala gtt ValI a ac Asn cag Gin cag Gin atc Ile gtt Val1 105 tgg Trp ate Ile cag Gin gag Giu gct Ala get Ala ctg Leu gaa Glu etc Leu gac Asp gac Asp gtt Val ci Pro ate Ile ga t Asp 170 gte cgc Val Arg ggc cag Gly Gin cac gte His Val ggc gta Gly Val ace atg Thr Met 75 cac ttg His Leu gtt cca Val Pro cag gat GIn Asp gaa gag Giu Glu 140 ace qea Thr Ala 155 ect gag Pro Glu tet gag Ser Glu ate cct Ile Pro 30 ace ate Thr Ile 45 aac get Asn Ala ate aag Ile Lys gac ctg Asp Leu gtt ate Val Ile 110 get gac Ala Asp 125 tte ac Phe Thr ge t gac Ala Asp ace etc Thr Leu ttc Phe 15 get Al a gac Asp gtt Val cac His Ct t Leu gte Val1 ace Thr gt Val1 ate Ile ate Ile 175 ggC Gly gtt Val eac His ct Leu ate Ile gee Ala gag Glu ate Ile tee Ser aag Lys 160 gte Val1 1 a ag Lys gtt Val ege Arg gag Glu gac Asp att Ile Gly aag Lys ate Ile 145 etc Leu aac As n ggc Gl y tac Tyr ace Thr etc Leu eag Gln aag Lys gag G iu gt t Val1 130 gaa Glu gag Glu ate Ile 115 163 211 259 307 355 403 451 499 547 595 643 get gte gag gaa gaa gac ace gaa gag gac Ala Val Glu Glu Giu Asp Thr Glu Glu Asp gaa gca get gaa gaa gea Glu Ala Ala Glu Glu Ala WO 01/00804 185 190 gct act gag taagcttttt tagatagctt tat Ala Thr Glu 200 <210> <211> 200 <212> PRT <213> Corynebacterium glutamicum PCTIIBOO/00922 <400> Met Ala Lys Tyr Gin Thr Ile Glu Ala 1 Lys ValI Arg Giu Asp Ile Gly Lys Ile 145 Leu Asri Ala GI y Tyr Thr Leu Gin Lys Glu Val1 130 Glu Glu Ilie Al a Ser Gi y Phe Asp Asn Arg Pro 115 Giu Gly Gly ValI Glu 195 Al a Al a Ala Ile Val1 Gi y 100 Ala Ala Leu Asp Leu 180 Glu 5 Arg Asp Ala Giu Leu Glu Pro Asp Glu Thr 165 Pro Ala Arg Val1 Leu Gly 70 Thr Lys Gi y ValI Leu 150 Thr Al a Al a Ala Glu Val 55 Gin Phe Val Thr Leu 135 Gly Leu Val1 Thr Arg Ser Arg Lys His Glu Met 120 Ser Al a Val1 Glu Glu 200 Val 25 Asri Gin Gin Ile Val 105 Trp Ile Gin Glu Giu 185 Al a Ala Leu Glu Leu Asp Asp Val1 Pro Ile Asp 170 Glu Arg Gin Val1 Val1 Met Leu Pro Asp Glu 140 Ala Glu Th r Glu Pro Ile Ala Lys Leu Ile 110 Asp Thr Asp Leu Glu 190 Gb y Val1 His Leu Ile Al a Glu Ile Ser Lys 160 Val1 Gi u <210> 11 <211> 1603 <212> DNA <213> Corynebacteriui glutamicum WO 01/00804 <220> <221> CDS <222> (1580) <223> RXA00605 <400> 11 ataggtaacc ctcataaaag gaaggaatgc taatg tct gag aag tca gca gca Met Ser Giu Lys Ser Ala Ala gac Asp acc Thr gca Ala a ag Lys gca Ala tcc Ser ct g Leu acc Thr 120 ggc Gly gac Asp aag Lys cag Gin cgc Arg ggc Gly ctc Leu aag Lys ga a Giu gct Ala 105 t gg T rp aac Asn 9gC GI y aac A.sn atc Ile cac His cca Pro gca Ala ggc Gly tac Tyr gt t Val cgc Arg tac Tyr atg Met gt Gly 170 gta Val1 aac Asn cag Gin cac His cac His acc Thr cgc Arg ga c Asp gac Asp aag Lys 155 ct g Leu ga t Asp gga Giy ggt Gly ttt Phe ggc Gly aag Lys ttc Phe gtc Val atc Ile 140 ttc Phe cgc Arg cgc Arg gca Ala cca Pro 45 aac Asn gct Ala gca Al a tCt Ser cac His 125 gt g Val1 ccg Pro gat Asp gga Gly cca Pro 30 aac Asn cgc Arg ttc Phe qac Asp act Thr 110 ggC Gi y ggt Gi y gac Asp gca Ala atg Met 15 gtt Val1 gtt Val1 gag Giu ggt Gly ctg Leu 95 gt t Val1 ttc Phe aac Asn ttc Phe gac Asp 175 cgt cca aag ctt tct gga aac act Arg cca Pro ctc Leu aac Asn gag Glu 80 ttc Phe gct Ala gct Ala aac Asn at c Ilie 160 atg Met Pro tct Ser aa t Asn gt t ValI 65 ctg Leu cag Gin ggt Gly ctt Leu acc Thr 145 ca c His cag Gin Lys gag Glu gac Asp cca Pro cac His c ct Pro gag Giu cgc Arg 130 cca Pro t ca Ser t gg Trp Leu Ser aac atc Asn Ile att cac Ile His gag cgt Giu Arg atc acc Ile Thr ggt aag Gly Lys 100 cag ggc Gin Giy 115 ttc tac Phe Tyr acc ttc Thr Phe cag aag Gin Lys gat 'ttc Asp Phe 180 Gly t cc Ser Ct C Leu atc Ile gag Giu gtc Val1 tcc Ser a cc Thr t tc Phe cgt Arg 165 tgg Trp Asn gca Al a att Ile cct Pro gac Asp acc Thr cca Pro gaa Giu ct t Leu 150 ctc Leu acc Th r PCT/IBOO/00922 53 101 149 197 245 293 341 389 437 485 533 581 629 gca cct gaa tct gca cac cag gtg acc tac ctg atg ggt gac cgc ggt Ala Pro Glu Ser Ala His Gin Val Thr Tyr Leu Met Gly Asp Arg Gly WO 01/00804 WO 0100804PCT/IBOO/00922 ace Thr 200 cag Gin a ag Lys gtt Val att Ile cct Pro 280 aag Lys atc Ile gca Al a cge Arg ege Arg 360 gag Glu get Ala ggc Gly aag acc Lys Thr ate aac Ile Asn cgc eag Arg Gin 235 ggc gag Gly Glu 250 aac ggc Asn Gly gag gat Giu Asp tgg tcc Trp Ser aae cgc Asn Arg 315 gat cca Asp Pro 330 etc cag Leu Gin ggc get Gly.Ala aae ace Asn Thr gge gag Gly Giu 395 ctg gat Leu Asp 410 tee Ser get Ala 220 9ge Gly aac Asn gac Asp gca Al a cag Gin 300 aa c Asn gge Gly gca Ala aac Asn tac Tyr 380 ect Pro aae Asn eac cag His Gin ggt aag Gly Lys gat tgc Asp Cys gac tac Asp Tyr 255 eea ate Pro Ie 270 aae tac Asn Tyr gat tae Asp Tyr ege aae Arg Asn ate gtt Ile Val 335 atc tte Ile Phe 350 cgc gac Arg Asp ege gaa Arg Giu tac age Tyr Sex aeg gat Thr Asp 415 gge Gly gt t Val1 225 ace Thr ege Arg ga e Asp tgg Trp ctg Leu 305 tte Phe gge Gly tae Tyr eea Pro tee Se r 385 aa c Asn tee Ser 677 725 773 821 869 917 965 1013 1061 1109 1157 1205 1253 1301 WO 01/00804 ggc cag gct gat gac atc tac gtc aac Gly Gin Ala Asp Asp Ile Tyr Val Asn 425 430 ctg gtt cgt gct gct tac gtc aag cac Leu Val Arg Ala Ala Tyr Vai Lys His 440 445 cag cca ggc atc cta tac cgc gag gtc Gin Pro Gly Ilie Leu Tyr Arg Giu Val 460 cga ttg gca gac aac atc tcc aac gca Arg Leu Ala Asp Asn Ile Ser Asn Ala 475 480 acc gag cca cgc gtc tac gac tac tgg Thr Glu Pro Arg Val Tyr Asp Tyr Trp 490 495 ggc gct cgc gtc aag gag ctt tac ctc Gly Ala Arg Val Lys Giu Leu Tyr.Leu 505 510 tgatttaaaa tga <210> 12 <211> 516 <212> PRT <213> Corynebacteriur glutamicum <400> 12 Met Ser Glu Lys Ser Ala Ala Asp Gin 1 Pro Lys Leu Ser Gly Asn Thr Thr Arg Ser Giu Asn Ilie Ser Ala Thr Ala Gly Asn Asp Ie His Leu Ile Giu Lys Leu Val Pro Giu Arg Ilie Pro His Ala Lys Leu His Ile Thr Giu Asp Val Ser Glu Gin Pro Gly Lys Vai Thr Pro Leu Ala 100 105 Gly Giu Gin Gly Ser Pro Asp Thr Trp 115 120 cc a Pro 435 gat Asp gag Giu ggc: Gly gt t ValI aag Lys 515 ggc acc gac Gly Thr Asp gac ttc atc Asp Phe Ile 455 gag aag gag Giu Lys Giu 47 0 tct gag gca Ser Giu Ala 485 gag aac ctc Giu Asn Leu taagtccttc PCT/IBOO/00922 1349 1397 1445 1493 1541 1590 1603 Leu Th r 145 His Gin Tyr Gly Val1 225 Thr Arq Asp Trp Leu 305 Phe Gly Tyr Pro Se r 385 Asn WO 01/00804 Arg Phe Tyr 130 Pro Thr Phe Ser Gin Lys Trp Asp Phe 180 Leu Met Gly 195 Phe Gly Ser 210 Trp, Val Lys Asp Ala Glu Glu Asp Leu 260 Val Lys Val 275 Asn Pro Phe 290 Ile Pro Val Ala Gin Ilie Val Gly Leu 340 Ala Asp Gin 355 Val Asn Arg 370 Met Gin Tyr Arg Tyr Asp Th r Phe Arg 165 Trp Asp His Tyr Ala 245 Tyr Gin A~sp Gly Giu 325 Ser Gl Pro Ile 45s 105 Giu Leu 150 Leu Thr Arg Thr His 230 Ala Asn Ile Leu Tyr 310 Gin Pro Arg Ile Phe 390 Gly Glu 135 Arg Asn Arg Gly Phe 215 Phe Lys Al a Met Thr 295 Phe Leu Asp Tyr Asn 375 Asp Al1a Gly Asp Lys Ala Thr 200 Gin Lys Val Ile Pro 280 Lys Ilie Ala Arg Arg 360 Glu Ala Giy Asn Gi y As n Pro 185 Pro T rp Thr Ala Glu 265 Phe Thr Leo Leu Met 345 Ile Val Glu Tyr Tyr Met Gly 170 Glu Lys Ile Arg Giy 250 Asn Giu Trp Asn Asp 330 Leo Gly Asn Gly Leo 410 Asp Lys 155 Leo Ser Thr Asn Gin 235 Giu Gly Asp Se r Arg 315 Pro Gin Al a Thr Glu 395 Asp Val Giy Pro Asp Asp Ala His Gin 190 Arg His 205 Glu Gly Trp Asp Ala Asp Phe Pro 270 Glu Asn 285 Lys Asp Pro Arg Asn Ile Arg Ilie 350 Tyr Arg 365 Ser Arg Ser Tyr Gly Thr PCT/IBOO/00922 Ser Ser Asn His Thr Ser Tyr 420 Gly. Gin 425 Ala Asp Asp Ile Tyr Vai Asn 430 WO 01/00804 Pro Asp Pro His 435 Gin Asp Asp Asp 450 Leu Asp Giu Gly 465 Met Gin Gly Ilie Asn Asn Val Asp 500 Gin Lys Lys Ala 515 PCT/IBOO/00922 Gly Thr Asp Leu 440 Asp Phe Ilie Gin 455 Giu Lys Giu Arg 470 Ser Giu Ala Thr 485 Giu Asn Leu Giy Val Arg Aia Ala Tyr Val Lys His 445 Pro Gly Ile Leu Tyr Arg Glu Val 460 Leu Ala Asp Asn Ile Ser Asn Ala 475 480 Glu Pro Arg Val Tyr Asp Tyr Trp 490 495 Ala Arg Vai Lys Glu Leu Tyr Leu.
505 510 <210> 13 <211> 2439 <212> DNA <213> Corynebacterium giutamicum <220> <221> CDS <222> (2416) <223> RXA00404 <400> 13 aagatccgat catcggcata cagaaacacc catctggccg catttctgca cacagtttct gcccgctqtt tctacgcata ccc gaa gag Pro Giu Glu atc aat gac Ile Asn Asp ggc gtg aag Gly Val Lys ctt gtc ttt Leu Val Phe tcc cgt ggc Ser Arg Gly gt a Val1 ttg Leu cc t Pro atc Ilie atc Ile 75 atc gtg Ile Val tac agc Tyr Ser atg tca.
Met Ser 45 gcg gtg Ala Vai tct. gtg Ser Val aactttcctt tttctgcatg gtg gct ttg aaa, cga Val Ala Leu Lys Arg 1 aaa cag act gac aac Lys Gin Thr Asp Asn act gac ctt cca gta Thr Asp Leu Pro Val gcc cgc gtt ggt ctc Ala Arg Val Gly Leu gga gca atc gct ttc Gly Ala Ile Ala Phe gtt ttg gcg gca gtt Val Leu Ala Ala Val WO 01/00804 WO 0100804PCT/IBOO/00922 gqt tcc tat atc att gcg ttt tct Gly Ser Tyr Ile Ile Ala Phe Ser ttc: tat gcc Phe Tyr Ala cga ctg att Arg Leu Ile gaa tac Glu Tyr 100 aa a Lys aa t Asn cac His atg Met 150 ggt Gly tct Ser atg Met atg Met gct Ala 230 gca Ala act Thr gct Al a t gg Trp gtt Val1 gac Asp cac His 135 gc Al a gtg Val act Thr ggc atc Ile 215 get Asp ctg Leu gaa.
Glu ggt Gly tct Ser gt t Val ggC Gly 120 ttt Phe gcg Ala att Ile cgt Arg acg Thr 200 etc Ile tca Ser ttc Phe gt g Vai ggt Gly 280 a eq Lys ag *Lys 105 aag Lys gca Ala ca g Gin ttc Phe agg Arg 185 gt c Val att.
Ile cc a Pro etg Met tcc Ser 265 tgg Trp1 acc Thr ccg Pro ga c Asp gct Ala atg Met gcc Ala 170 cgt Arg ggt Gly at c Ile t gg Trp ggt Gly 250 atc Ile gt t Val1 act rhr aaa Lys tat Tyr att Ile Gly 155 ggt Gly gga Gly gga Gi y gcg Al a 9gc Gly 235 gt g Val1 atc Ile gca Ala ttg Leu gat Asp gtc Val1 gca Ala 140 tac Tyr gca Al a cgc Arg gct Ala gtg Val 220 gt t Val tac Tyr ggt Gly gac A.sp ;cg 1 a ceq Glrn cca Pro 125 gg t Gly ctg Leu qtg Val1 tca Ser gcc Ale 205 ct c Leu ttc Phe t tg Leu gtg Val acc Thr 285 ttg cga Arg 110 acg Thr gcc Ala cca Pro cag Gin ctt Leu 190 ggt Gi y gca Ala tcC Ser cgt Arg gca Al a 270 tca Ser gc gca Ala gat Asp gg t Gly 9gc Gly ga c Asp 175 ggc Gi y etc Ile t tg Leu atc Ile tec Tyr 255 ct g Le u Lgg rrp Ltg acc Thr cgt Arg c ca Pro ecc Thr 160 tec Tyr cag Gin ttg Leu etc Ile acc Thr 240 ctg Leu ct c Leu ggc Gly atc ccg *Pro cgt Arg ttg *Leu 145 t tg Leu ct a Leu atg Met gcg Ala gtg Val 225 atg Met cgc Arg ct g Leu gtg Val ggt Gly 305 gcg Ala gtg Val 130 gtt Val1 tgg Trp gt g Val1 gt t ValI acc Thr 210 gtt Val acc Thr cca Pro ctg Leu geaa Glu 290 t ac Tyr gaa Glu 115 ct t Leu gga Gi y ett Ile ctg Leu cgt Arg 195 etc Ile eat Asn etc Ile ggt Gly gct.
Ala 275 t gg Trp gge Gly tac Tyr ttt Phe cc t Pro etc Ile t gg T rp 180 get Asp t cc Ser gce Ale cca Pro cgt Arg 260 etc Ile ttc Phe etc Ile gt t Val Gly gtc Val1 ctc Leu 165 gtg Val1 gee Glu etc: Ile ct g Leu att.
Ile 245 gt t Val1 gt t Val1 acc Thr atg Met 403 451 499 547 595 643 691 739 787 835 883 931 979 1027 1075 Leu Ala Leu Ile 295 300 gct gcg att ttg ccg gtg tgg ctg ctg ctt gca ccg cgc get tac ctg WO 01/00804 WO 0100804PCT/IBOO/00922 Ala Ala Ilie Leo Pro Val Trp Leo Leu Leu Ala Pro Arg Asp Tyr 310 315 320 t ct Ser ttg Leo ct t Leo ttc Phe tct Se r 390 atg Met gca Al a aac Asn t gg Trp ctg Leo 470 acc Thr gga Gi y atc Ile acc Thr ttc Phe gag Glu etc Ile 375 tca Ser ctc Leo ctg Leu gct Ala gt t Val1 455 t cg Ser ggt Gly ttC Phe a tg Met ttt Phe gca Al a qgc Gly 360 acg Thr gga Gly 9gC Gly etc Ilie ccg Pro 440 aac Asn gaa Glu Gly etc Ile ttt Phe 520 at g Met cgt Arg 345 ac Asn att Ilie acc Thr tac Tyr acc Tb r 425 ctg Leo t cc Ser gct Ala gca Ala ggc Gly 505 gag Glu eag Lys 330 cct Pro ggt Gly gcc Ala aca Tb r Gly 410 gct Ala gca Ala at t Ile gct Al a cca Pro 490 ggc Gly gct Ala etc Ile gag Glu ccg Pro tgt Cys cca Pro 395 9gC Gly gtt Val ct g Leo ggg Gly gaa Glu 475 acc Thr gct Ala ctg Leu ggc Gi y gt g Val1 gt g Val ggt Gi y 380 a eq Lys atg Met att Ile act Thr ctg Leo 460 agt Ser t tg Leu gga.
Gi y ttc Phe gtc Val cag Gin t tc Phe 365 gca Ala ct t Leo ttg Leu ctg Leo ggt Gly 445 ace Thr gtc Val1 gcg Ala at g Met etc Ile 525 atc Ile atg Met 350 tet Se r .ctg Leo gtg ValI atg Met gat Asp 430 gga Gly ggt Gly gga.
Gi y ttc Phe eag Lys 510 ctc Leu ggt Gi y 335 cct Pro gga Gb y tct Ser gag Glu gee Glu 415 cgt Arg get Asp gcg Al a ga a Glu ggt Gly 495 gcg Ala act Thr ctg Leo tcc Ser agt Ser ggt Gly aag Lys 400 tct Ser cac His cce Pro get Asp t cc Ser 480 atg Met ttc Phe act Thr ttg Leo gtg Val ctg Le u ttc Phe 385 geaa Glu ttc Phe ct g Leo gca Ala etc Ile 465 act Thr tct Ser tgg Trp gt g Val1 gtg Val1 t cc Ser 355 c ca Pro gce Ala cag Gin gcg Ala ttc Phe 435 gca Al a ccg Pro att Ile etc Ile cac His 515 gca Ala ggt Gly 340 ttC Phe ttc Phe ct g Leo at g Met atg Met 420 tcc Ser gct Ala gee Glu tcc Ser ctc Leo 500 ttc Phe ggt Gly 1123 1171 1219 1267 1315 1363 1411 14.59 1507 1555 1603 1651 1699 1747 cgt gtg gct Arg Val Ala cgc ttt atg atg acc get acc ttg Arg Phe Met Met Thr Asp Thr Leo ggc eat gtt cca. ggt Gly Asn Val Pro Gly WO 01/00804 PTIO/02 PCT/IBOO/00922 ct g Leu 550 acc Th r acc Thr got Ala gtg Val ttg Leu 630 ttc Phe ogo Arg cct Pro ttg Leu att Ile 710 ttg Leu act Thr cgo Arg gtg Val1 gat Asp aac Asn gtg Val 615 gca Ala cac His gat Asp gag Giu t cc Ser 695 gcg Ala gag Gi u gga Gi y cgt Arg ttt Phe cca Pro cag Gin 600 aag Lys tgg Trp tct Ser gca Al a gca Ala 680 atc Ile gt g Val aco Thr ttc Phe ttC Phe gtg Val1 otg Leu 585 ctg Leu aag Lys gat Asp gat Asp aag Lys 665 at 0 Ile ctg Leu t gc Cys act Thr ct t Leu 745 *aag Lys tgt Cys 570 ggc Gl y otc Leu ggc Gly cto Leu ccg Pro 650 tot Ser gat Asp ttc Phe atc Ile gaa I Glu 730 gca Ala gat Asp 555 gct Ala ggc Gly gcc Ala cig Leu att Ile 635 gct.
Al a ca a Gin gcg Ala gcg Al a aag Lys 715 ga g Glu tct Se r cct Pro ct a a tc Ile gct Ala tac Tyr 620 gt c ValI att Ile Gly gtt Val1 gtg Val 700 t cc Se r cct Pro too Ser t ca Ser t gg Trp aac As n att Ile 605 aag Lys acg Thr 9gC Gly ctt Leu at c Ile 685 Oto Leu atc Ile ga t Asp agg Arg t gg Trp ggt Gly gtg ValI 590 goa Ala tgg Trp atg Met tac Tyr acc Thr 670 cga Arg gtC Val agg Arg act Thr qa t Asp 750 act Thr gct Ala 575 ott Leu ctt Leu 9gg Ala act Th r tgg Trp 655 ga a Giu aac Asn ctc Leu gct Al a ga a Glu 735 aag Lys gtc ggt Val Gly 560 att ttg Ile Leu ttc cca Phe Pro got otc Ala Leu tgg att Trp Ile 625 gog tca Aia Ser 640 gct cag Ala Gin ttt ggt Phe Gly aco atg Thr Met gtt gtt Val Val 705 cgt goa.
Arg Ala 720 tot gag Ser Giu gaa gto Glu Val aac Asn oto Leu ota Leu gtg Val1 610 o ca Pro tgg Trp aao Asn gc Ala att Ile 690 gt 0 ValI gc Al a tto Phe oag Gln att Ile ggt Gi y 580 ggt Gly gt t Val1 gtt Val1 aag Lys aao Asn 660 aaa Lys 9go Gly goa Ala aoa Thr gc Al a 740 atg Met 1795 1843 1891 1939 1987 2035 2083 2131 2179 2227 2275 2323 2371 2416 gao gag Asp Giu ogc tao oca ggc ggt gog 000 gtg tot tot Arg Tyr Pro Gly Gly Ala Pro Val Ser Ser 760 765 gga ggg cac Gly Gly His 770 WO 01/00804 taaaacatga tggctcttac tca.
<210> 14 <211> 772 <212> PRT <213> Corynebacterium glutamicum <400> 14 Val Ala Leu Lys Arg Pro Glu Glu Lys PCTIIBOO/00922 2439 1 Lys Th r Ala Gly Val1 Arg Pro Arg Leu 145 Leu Leu Met Ala Val1 225 Gin Asp Arg Ala Leu Leu Al a Val1 130 Val Trp Val Val Thr 210 ValI Thr Asp Leu Pro Val Gly Ile Ala Ala Ala Ile Glu 100 Glu Tyr 115 Leu Phe Gly Pro Ile Ilie Leu Trp 180 Arg Asp 195 Ile Ser Asn Ala 5 Asn Val1 Leu Phe Val1 Tyr Val1 Gly ValI Leu 165 Val1 Giu Ile Leu Ile Gly Leu Se r 70 Gly Lys Asn His Met 150 Gly Ser Met Met Ala 230 Asn Val Val1 Arg Ser ValI Asp His 135 Ala Val1 Thr Gly Ile 215 Asp Asp Asp 25 Lys Lys Phe Gly Gly.Giu Tyr Ile Val Lys 105 Gly Lys 120 Phe Ala Ala Gin Ile Phe Arg Arg 185 Thr Val 200 Ile Ile Ser Pro Thr Val 10 Asp Leu Ser Pro Val Ile Thr Ile Ile Ala 90 Pro Lys Asp Tyr Ala Ile Met Gly 155 Ala Gly 170 Arg Gly Gly Gly Ile Ala Trp Gly 235 Val Ser Ser Val1 Val1 Phe Arg 110 Thr Ala Pro Gin Leu 190 Gly Al a Se r Thr Asn Pro Gi y Trp Tyr Al a Asp Gly Gly Asp 175 Gly Ile Leu Ile Met Thr Ile Pro Ile Ala Leu Phe Met 245 Gly 250 Val Tyr Leu Arg Tyr Leu 255 WO 01/00804 WO 0100804PCT/IBOO/00922 Arg Pro Gly Arg Val Thr Glu Val Ser Ile Ile Gly Val Ala Leu Leu 260 265 270 Leu Leu Ala Ile Val Ala Giy Gly Trp Val Ala Asp Thr Ser Trp Gly 275 280 285 Val Giu Trp Phe Thr Trp Ser Lys Thr Thr Leu Ala Leu Ala Leu Ile 290 295 300 Gly Tyr Gly Ilie Met Ala Ala Ile Leu Pro Val Trp Leu Leu Leu Ala 305 310 315 320 Pro Arg Asp Tyr Leu Ser Thr Phe Met Lys Ile Gly Val Ile Gly Leu 325 330 335 ,Leu Ala Val Gly Ile Leu Phe Ala Arg Pro Giu Val Gin Met Pro Ser 340 345 350 Vai Thr Ser Phe Ala Leu Giu Gly Asn Gly Pro Val Phe Ser Gly Ser 355 360 365 Leu Phe Pro Phe Leu Phe Ilie Thr Ilie Ala Cys Gly Ala Leu Ser Gly 370 375 380 Phe His Ala Leu Ile Ser Ser Gly Thr Thr Pro Lys Leu Val Glu Lys 385 390 395 400 Giu Ser Gin Met Arg Met Leo Gly Tyr Gly Gly Met Leo Met Giu Ser 405 410 415 Phe Val Ala Met Met Ala Leu Ile Thr Ala Val Ile Leu Asp Arg His 420 425 430 Leu Tyr Phe Ser Met Asn Ala Pro Leu Ala Leo Thr Gly Gly Asp Pro 435 440 445 Ala Thr Ala Ala Giu Trp Val Asn Ser Ile Gly Leu Thr Gly Ala Asp 450 455 460 Ile Thr Pro Glu Gin Leu Ser Glu Ala Ala Giu Ser Val Gly Giu Ser 465 470 475 480 Thr Vai Ile Ser Arg Thr Giy Giy Ala Pro Thr Leu Ala Phe Gly Met 485 490 495 Ser Glu Ile Leu Ser Giy Phe Ile Gly Giy Ala Gly Met Lys Ala Phe 500 505 510 Trp Tyr His Phe Ala Ile met Phe Glu Ala Leu Phe Ile Leu Thr Thr 515 520 525 Val Asp Ala Gly Thr Arg Val Ala Arg Phe Met Met Thr Asp Thr Leu 530 535 540 Gly Asn Val Pro Gly Leu Arg Ar g Phe Lys Asp Pro Ser Trp Thr Val 545 550 555 560 Gly Leu Pro Leu Ile 625 Ser Gin Gi y Met Val 705 Ala Glu Val WO 01/00804 Asn Trp Ile Leu Met Gly 580 Leu Phe Gly 595 Val Leu Val 610 Pro Ala Val Trp Gin Lys Asn Ala Asn 660 Ala Ala Lys 675 Ilie Gin Gly 690 Val Gly Ala Ala Gly Thr Phe Phe Ala 740 Gin Ala Met Ser 565 Val1 Ile Val1 Pro Ile 645 Phe Ser Ile Al a Pro 725 Pro rrp Thr Val Thr Asp Ala Asn Val Val 615 Leu Ala 630 Phe His Arg Asp Pro Glu Leu Ser 695 Ile Ala 710 Leu Glu Thr Gly Phe Val Pro Leu 585 Gin Leu 600 Lys Lys Trp Asp Ser Asp Ala Lys 665 Ala Ile 680 Ile Leu Val Cys Thr Thr Phe Leu 745 Cys 570 Gly Leu Gi y Leu Pro 650 Ser Asp Phe Ile Glu 730 Ala PCT/IBOO/00922 Asp Glu Arg Tyr Pro Gly Gly Pro Val Ser 755 760 b Ser Gly Gly His 770 <210> <211> 255 <212> DNA <213> Corynebacteriun glutamicum <220> <221> COS <222> (232) <223> RXNO3ii9 <400> tgggaggtgt cgcaccaagt acttttgcga agcgccatct gacggatttt caaaagatgt WO 01/00804 atatgctcgg tgcggaaacc tacqaaagga ttttttaccc atg gct gta tac gaa Met Ala Val Tyr Glu 1 ctc cca gaa ctc gac tac gca tac gac gct ctc gag cca cac atc gtc Leu Pro Glu Leu Asp Tyr Ala Tyr Asp Ala Leu Glu Pro His Ile Val 15 gct gaa atc atg gag ctt gac cag tcc aag gac cac gca acc tac gtt Ala Glu Ile Met Glu Leu Asp Gln Ser Lys Asp His Ala Thr Tyr Val 30 gcg ggc gca aat gca gca ctc taggcactag agaaggcacg cga Ala Gly Ala Asn Ala Ala Leu <210> 16 <211> .44 <212> PRT <213> Corynebacterium glutamicum <400> 16 Met Ala Val Tyr Glu Leu Pro Glu Leu Asp Tyr Ala Tyr Asp Ala Leu 1 5 10 Giu Pro His Ilie Val Ala Giu Ile Met Glu Leu Asp Gln Ser Lys Asp 25 His Ala Thr Tyr Val Ala Gly Ala Asn Ala Ala Leu PCTIIBOO/00922 115 163 211 255 <210> 17 <211> 249 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> (226) <223> RXN03120 <400> 17 ctgggcagtt cttgggtacg accacatatc cggtcgcctg gttatcgagc agctcaccga ccaggagggc aacatctcct tcgacatcac cccagttctg atg ctc gat atg tgg Met Leu Asp Met Trp 1 gag cac gct ttc tac ctg cag tac atg aac gtt aag gca gat tac gtc Glu His Ala Phe Tyr Leu Gin Tyr Met Asn Val Lys Ala Asp Tyr Val 15 aag gct gtt tgg aac gtc ttc aac tgg gac gac gca aga gca cgc ttc Lys Ala Val Trp Asn Val Phe Asn Trp Asp Asp Ala Arg Ala Arg Phe 30 WO 01/00804 gca gca gct tcc aag taagcatttt tagtccgtgc aat Ala Ala Ala Ser Lys PCTIIBOO/00922 249 <210> 18 <211> 42 <212> PRT <213> Corynebacterium glutamicum <400> 18 Met Leu Asp Met Trp Glu His Ala Phe Tyr Leu Gin Tyr Met Asn Val 1 5 10 Lys Ala Asp Tyr Val Lys Ala Val Trp Asn Val Phe Asn Trp Asp Asp 25 Ala Arg Ala Arg Phe Ala Ala Ala Ser Lys <210> 19 <211> 660 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> (637) <223> RXN00575 <400> 19 gaagcgtccg caggcaagaa aacgtcccgg aaaacggcga ccggttgccg atctatttaa ataccaggac aattgcgtgc ttc Phe atc Ile ggt Gi y a tg Met tct Ser act Thr tac Tyr ccc Pro gtg Val gct Ala cga Arg ttg Leu tgg Trp gt a Val1 cca Pro gag Glu acg Thr tcC Ser gac Asp cga Arg ggt Gly gga Gly 30 ca a Gin ccg Pro cag Gin tagggg-tcac ccgcgcatgt atg gtt gaa aga gac Met Val Glu Arg Asp 1 cct cag gtg agg gac Pro Gin Val Arg Asp act tat gag act tct Thr Tyr Glu Thr Ser atc atg gat acc gtc Ile Met Asp Thr Val atc ctc qga tgg gtg Ile Leu Gly Trp Val cat gga gtg gtg gaa His Gly Val Val Glu 115 163 211 259 307 355 WO 01/00804 PCT/IBOO/00922 75 80 gat tcc atc tat atc cac ccc cag ggc caa ggc cga gga atc ggc ggc 403 Asp Ser Ile Tyr Ile His Pro Gin Gly Gin Gly Arg Gly Ile Gly Gly 95 100 gct tig ctc gac gcc ctt atc acc tac tgc gaa agc aac ggc atc tgg 451 Ala Leu Leu Asp Ala Leu Ile Thr Tyr Cys Glu Ser Asn Giy Ile Trp 105 110 115 tcg atc cac tcc tgg atc ttc ccg gaa aac ctc ggt tct gcg aaa ctg 499 Ser Ilie His Ser Trp Ilie Phe Pro Giu Asn Leu Gly Ser Ala Lys Leu 120 125 130 cat gaa tcg aag ggc ttc gtg aag gtg ggc acc atg cac caa atg gca 547 His Glu Ser Lys Giy Phe Val Lys Vai Gly Thr Met His Gin Met Aia 135 140 145 agg atg ccc tac ggc gag atg gaa gga caa tgg cgc gat tgt gat ctg 595 Arg Met Pro Tyr Gly Giu Met Giu Giy Gin Trp Arg Asp Cys Asp Leu 150 155 160 165 tgg gag tgc ctc tta tcc gtt cca gag caa gct caa agt tcc 637 Trp Glu Cys Leu Leu Ser Val Pro Giu Gin Ala Gin Ser Ser 170 175 taaagcaatt taaatctgac itt 660 <210> <211> 179 <212> PRT <213> Corynebacterium giutamicum <400> Met Val Giu Arg Asp Phe Thr Ile Arg Pro Ile Arg Giu Giy Asp Phe 1 5 10 Pro Gin Val Arg Asp Ilie Tyr Giu Leu Gly Leu Glu Thr Gly His Mla 25 Thr Tyr Giu Thr Ser Gly Pro Thr Trp Asp Gin Phe Ser Gin Ser Lys 40 Ile Met Asp Thr Vai Met Val Aia Val Giu Asn Asn Asp Pro Asp Phe 55 Ilie Leu Gly Trp Val Ser Ala Ala Pro Ile Ser Ser Arg Gin Vai Phe 70 75 His Giy Vai Vai Giu Asp Ser Ile Tyr Ile His Pro Gin Giy Gin Gly 90 Arg Giy Ilie Gly Giy Ala Leu Leu Asp Ala Leu Ile Thr Tyr Cys Giu 100 105 110 Ser Asn Giy Ile Trp Ser Ile His Ser Trp Ile Phe Pro Giu Asn Leu WO 01/00804 PCTIBOOIOO922 115 120 125 Gly Ser Ala Lys Leu His Giu Ser Lys Gly Phe Val Lys Val Gly Thr 130 135 140 Met His Gin Met Ala Arg Met Pro Tyr Gly Glu Met Glu Gly Gin Trp 145 150 155 160 Arg Asp Cys Asp Leu Trp Giu Cys Leu Leu Ser Val Pro Giu Gin Ala 165 170 175 Gin Ser Ser <210> 21 <211> 606 <212> DNA <213> Corynebacterium giutamicum <220> <221> CDS <222> (583) <223> FRXA00575 <400> 21 gcatgtccgg ttgccgatct atttaaatae eaggacaatt cttcactatc cgaccaatcc gcgagggtga tttccctcag gcgtgcatgg ttgaaagaga gtg agg gac atc tac 11! Val Arg Asp Ile Tyr gaa Glu acg Thr g eg Ala get Ala atc Ile etc Leu cac t tg Leu t gg Trp gta Val1 cca Pro tat Tyr gac Asp tcC ggc ctg Gly Leu gac cag Asp Gin gaa aac Glu Asn att tea Ile Ser atc cac Ilie His gcc ctt Ala Leu tgg atc a eq Thr tee Ser gac Asp cga Arg cag Gin 75 ace Thr ccg gga cat Gly His caa tet Gin Ser ccg gac Pro Asp cag gtt Gin Val 60 ggc eaa Giy Gin tac tge Tyr Cys gaa aac gcg act Ala Thr aaa atc Lys Ile 30 tte ate Phe Ile tte eat Phe His ggc ega Gly Arg gaa age Glu Ser etc ggt tat Tyr atg Met etc Leu gga Gly gga Giy aac As n tet 1 gag Glu gat Asp gga Gly gtg Val1 ate Ile Gly geg tct S er gtc Val1 gtg Val gaa Giu Gly tgg Trp etg ggt Giy at g Met tct Se r gat Asp get Ala t eg Ser 100 cat WO 01/00804 His Ser Trp Ile Phe Pro Glu Asn Leu 105 110 tcg aaq ggc ttc gtg aag gtg ggc acc Ser Lys Gly Phe Val Lys Val Gly Thr 120 125 ccc tac ggc gag atg gaa gga caa tgg Pro Tyr Gly Giu Met Giu Gly Gin Trp 135 140 tgc ctc tta tcc gtt cca gag caa gct Cys Leu Leu Ser Val Pro Giu Gin Ala 150 155 taaatctgaC ttt <210> 22 <211> 161 <212> PRT <213> Corynebacterium gluta.micum <400> 22 Val Arg Asp Ile Tyr Glu Leu Gly Leu 1 5 Giu Thr Ser Gly Pro Thr Trp Asp Gin 25 Asp Thr Val Met Val Ala Val Glu Asn 40 Gly Trp Val Ser Ala Ala Pro Ile Ser 55 Val Val Giu Asp Ser Ile Tyr Ile His 70 Ile Gly Gly Ala Leu Leu Asp Ala Leu Gly Ile Trp Ser Ie His Ser Trp Ilie 100 105 Ala Lys Leu His Giu Ser Lys Gly Phe 115 120 Gin Met Ala Arg Met Pro Tyr Gly Glu 130 135 Cys Asp Leu Trp Giu Cys Leu Leu Ser 145 150 Ser PCT/IBOO/00922 Gly Ser Ala Lys Leu His Giu 115 atg cac caa atg gca agg atg Met His Gin Met Ala Arg Met 130 cgc gat tgt gat ctg tgg gag Arg Asp Cys Asp Leu Trp Giu 145 caa agt tcc taaagcaatt Gin Ser Ser 160 Giu 10 Phe Asn Ser Pro Ile 90 Phe Vali Met Val1 Thr Ser Asp Arg Gin 75 Thr Pro Lys Giu Pro 155 Giy Gin Pro Gin Gi y Tyr Gi u Val1 Gly 140 Giu His Ala Ser Lys Asp Phe Val Phe Gin Giy Cys Giu Asn Leu 110 Gly Thr 125 Gin Trp Gin Ala Thr Tyr Ile Met Ile Leu His Gly Arg Giy Ser Asn Giy Ser Met His Arg Asp Gin Ser 160 WO 01/00804 <210> 23 <211> 1575 <212> DNA '213> Corynebacterium glutamicum <220> <221> CDS <222> (1552) <223> RXN01345 <400> 23 cataacctca ttqaacatqc aaaactaatg cttttggggg PCTIBOO/00922 gtatgcataa attcgtttcg ttccactgca cagcccgaaa atgctgctag ggtcaagttc atg cgt ttt Met Arg Phe gac ttg Asp Leu tat ccc Tyr Pro att cca Ile Pro gat gct Asp Ala aaa cgc Lys Arg ttg ggc Leu Gly gaa aac Giu Asn acc tcc Thr Ser gcc cag Ala Gin 135 gga Gi y atc Ile tct Ser att Ile cta Leu gat Asp gtg Vali ccg Pro 120 cga Arg act Thr gtc Val1 gtg Val1 gag Gi u ct C Leu cat His gtc Val 105 atc Ile ct g Leu acc Thr act Th r gtg Val1 gtt Vai t ct Ser gt a Val1 act Thr gaa Giu ctc Leu cgc Arg gtg Val1 gcc Ala ggg Gly gaa Glu 75 cac His gcg Ala gta Vai B CC rhr aca atc Thr Ile gaa gat Glu Asp ctc aag Leu Lys 45 cag gac Gin Asp ccc aat Pro Asn cct ttg Pro Leu ctg Cgt Leu Arg gtc att Val Ile 125 atg tcc Met Ser 140 gcg Ala tct Se r 30 gca Al a ca C His gtc Val ggc Gly gca Ala 110 ggt Gi y gcc A~la gcc gcc Ala Ala 15 tta ggc Leu Gly gat agg Asp Arg cct tcc Pro Ser acg gaa Thr Glu 80 gcc gtc Aia Val 95 ttt cag Phe Gin gtg ccc Val Pro ttC agc Phe Ser gac Asp acc Th r gtc Val1 gta ValI acc Thr gag Glu ca a Gin aa C Asn 130 aca Thr cgc Arg cac His gcg Ala cgt Arg ccg Pro gct Al a ttg Leu 115 tcc Ser ggC Gly qga Ctt Gly Leu gga aac Gly Asn gat ttc Asp Phe ggt tgg Gly Trp tCt ttc Ser Phe gtc tac Val Tyr ttt gcg Phe Ala 100 gga gat Gly Asp cac agc his Ser atC acc Ile Thr 115 163 211 259 307 355 403 451 499 547 595 gtt gtc ggt ttg gtc aat gag ccc agc gcc gca Val Val Gly Leu Val Asn Giu Pro Ser Ala Ala 150 155 160 gct ttc gag tac ac Ala Phe Glu Tyr Thr WO 01/00804 WO 0100804PCTIIBOOIOO922 cac cgc cac H is tat T yr 9gC Gi y Gi y GI y 230 gac Asp ttg Leu ttC Phe gaa Glu ate Ile 310 ctc Leu ggt Gly ttc Phe His ttg Leu cac His 200 gat Asp cag Gin tcC Ser ct a Leu gag Glu 280 ctc Leu ct t Leu gag Glu act Thr cta Leu 360 gcc A1a gga Gly 185 cac His ttc Phe cac His cgc Arg ga a Glu 265 gct Ala ate Ile gtt Val cgt Arg gcg Al a 345 agg Arg cgc acc tia aac tcc aag cgc caa gcc atc Arg 170 ggC Gly gag Giu gat Asp ga t Asp aac As n 250 att Ile gee Ala 9gC Gly ggt Gly ttC Ph e 330 gt g ValI gac Asp Thr gga Gly gt t Val gaa Glu gcg Ala 235 gcg Ala ggC Gly act Thr gtC Val1 gga Gl y 315 ggC GI y ggt Gly cgc A.rg Leu aca Th r gt g Val1 ate Ile 220 t tt Phe aag Lys gac Asp ccc Pro ga t Asp 300 gga Gly cgc Arg ctg Leu gtt Val Asn ttc Phe t cc Ser 205 ct c Leu ggC Gi y ga a Glu gac Asp ctg Leu 285 ga t Asp t cc Ser cgt Arg gee Al a gcg Alia 365 Se r ga c Asp 190 tcC Ser ctc Leu aag Lys gct Ala gac Asp 270 gtg Val1 ctt Leu tcg Se r gt C Val1 ate Ile 350 cga Arg Lys 175 tcc Se r att Ile caa Gin cgt Arg ctt Leu 255 ate Ile gaa Gi u aaa Lys ct C Leu cac His 335 gcg Ala ggc Gly Arg Gin tcg ctc Ser Leu ggc att Gly Ile tgc gcg Cys Ala 225 gct aaa Ala Lys 240 gtt ccg Val Pro ace gtt Thr Val aaa tee Lys Ser gat tcc Asp Ser 305 cca ctc Pro Leu 320 cgc tcc Arg Ser gct gac Ala Asp ate ggt Ile Gly Ala atec Ile tca Ser 210 Ctc Leu aac Asn caa Gin cca Pro ttg Leu 290 gac Asp gtt Val cca Pro cct Pro gt g Val1 370 Ile cgc Arg 195 cgc Arg aag Lys a cq Thr t cc S er gtg Val 275 t cc Ser ate Ile tcc Ser ttC Phe t cC Se r 355 ttC Phe gtg gtt Val Val 180 atc gac Ile Asp ctt ggt Leu Gly gcc gca Ala Ala ctt ctc Leu Leu 245 cgt cgc Arg Arg 260 aac aag Asn Lys ate atg Ile Met gca ggc Ala Gly agg ttg Arg Leu 325 ccc tca Pro Ser 340 tct *ggt Ser Gly cgt gag Arg Giu 643 691 739 787 835 883 931 979 1027 1075 1123 1171 1219 1267 cac gat tct ggt His Asp Ser Gly 375 cgt gcc gtg agc ttt gac ccg ctg. atc gcc ccg gac Arg Ala Val Ser Phe Asp Pro Leu Ile Ala Pro Asp WO 01/00804 aec gat tet gcg ace gtg geg aaa ega Thr Asp Ser Ala Thr Val Ala Lys Arg 390 395 att ggt tgg ttC agg ttc gtg gaa tac Ile Gly Trp Phe Arg Phe Val Glu Tyr 410 agc ccc gga gat att tcc ctg etc agt Ser Pro Gly Asp Ile Ser Leu Leu Ser 425 430 age tee atc acc gat gtg gat get ace Ser Ser Ile Thr Asp Val Asp Ala Thr 440 445 eca qaa gta gaa gaa ace atc aca gte Pro Glu Val Glu Glu Thr Ile Thr Val 455 460 att tee ate aag ata etc gge ggc gtt Ile Ser Ile Lys Ile Leu Gly Gly Val 470 475 tagttaccat tttggtgetg gtg <210> 24 <211> 484 <212> PRT <213> Corynebacterium glutamieun <400> 24 Met Arg Phe Gly Leu Asp Leu Gly Thr 1 5 Val Asp Arg Gly Asn Tyr Pro Ile Val 25 Asp Thr His Asp Phe Ile Pro Ser Val 40 Ile Val Ala Gly Trp Asp Ala Ilie Glu 55 Phe Val Arg Ser Phe Lys Arg Leu Leu 70 Ala Thr Pro Val Tyr Leu Gly Asp His Leu Glu Ala Phe Ala Glu Asn Val Val 100 105 Thr Gin Leu Gly Asp Thr Ser Pro Ile C 115 120 tge tac Cys Tyr 400 tee ace Ser Thr 415 gaa ate Glu Ile gag att Glu Ile aat gac Asn Asp ace gte Thr Val 480 PCT/IBOO/00922 aae 1315 Asn 405 gge 1363 Gly gat 1411 Asp ggc 1459 Gly tee 1507 Ser 1552 1575 Tb r 10 Thr Val1 Val1 Ser Val1 90 Phr ;iu Thr Ile Glu Asp Leu Lys Gin Asp Pro Asn Pro Leu Leu Arg Val Ile 125 Ala Ala Ser Leu Ala Asp His Pro Val Thr Gly Ala Ala Phe 110 Gly Val Ala Gly Arq Ser Glu Val1 Gin Pro WO 01/00804 Ala Asn Ser His 130 PCT/1B00100922 Ser Ala Gin Arg Leu Leu Thr Met Ser Ala Phe Ser 135 140 Ala Thr Gly Ile Thr Val Val Gly r 145 Ala Gin Leu Ile Ala 225 Lys Pro Va1 Ser Ser 305 Leu Ser Asp Phe Ala Ile Ser 210 Leu Asn Gin Pro Leu 290 Asp Val Pro Pro Glu Ile Arg 195 Arg Lys Thr Ser Va1 275 Ser Ile Ser Phe Ser 355 Tyr Val 180 Ile Leu Ala Leta Arg 260 Asn Ile Ala I Arg Pro 340 Ser C Thr 165 Val Asp Gly Ala Leu 245 Arg Lys Met Gly Leu 325 3er ;ly 15C His Tyr Gly Gly Gly 230 Asp Leu Phe Glu Ile 310 Leu Gly Phe Arg Asp Thr Asp 215 Arg Glu Val Tyr Pro 295 Tyr Arg Ser His His Leu His 200 Asp Gln Ser Leu Glu 280 Leu Leu Glu Thr Leu 360 Let Ala G1 185 His Phe His Arg Glu 265 Ala Ile Val Arg A1a 345 krg 1 Val Arq 170 r Gly Glu Asp Asp Asn 250 Ile Ala Gly Gly Phe 330 Val Asp Arg Asn Glu 155 Thr Leu Gly Thr Val Val Glu Ile 220 Ala Phe 235 Ala Lys Gly Asp Thr Pro Val Asp 300 Gly Gly 315 Gly Arg Gly Leu Arg Val Ala Val 380 Val Ala I 395 Phe Val Pro Asn Phe Ser 205 Leu Gly Glu Asp Leu 285 Asp Ser Arg Ala Ala 365 Ser Lys ;lu Sex Ser Asp 190 Ser Leu Lys Ala Asp 270 Val Leu Ser Va1 Ile 350 Arg Phe Arg Tyr Ala Lys 175 Ser Ile Gin Arg Leu 255 Ile Glu Lys Leu His 335 Ala Gly Asp Cys Ser Ala 160 Arg Ser Gly Cys Ala 240 Va1 Thr Lys Asp Pro 320 Arg Ala Ile Pro ryr 400 Thr Gly Val Phe Arg Glu His Asp Ser Gly 370 375 Leu Ile Ala Pro Asp Thr Asp Ser Ala Thr 385 390 Lys Ala Vai His Asn Ile Gly Trp Phe Arg 405 410 415 Val Ser Glu Gly Ser Pro Gly Asp 425 Ile Ser Leu Leu Ser Glu Ile 430 WO 01/00804 PCT/IBOO/00922 Lys Ile Pro Phe Asp Ser Ser Ile Thr Asp Val Asp Ala Thr Glu Ile 435 440 445 Ser Arg Phe Asp Gly Pro Giu Val Glu Glu Thr Ile Thr Val Asn Asp 450 455 460 Asn Gly Val Ala Ser Ilie Ser Ile Lys Ile Leu Gly Gly Val Thr Val 465 470 475 480 Giu His Thr Ile <210> <211> 1267 <212> DNA <213> Corynebacterium giutamicum <2 <221> CDS <222> (1267) <223> FRXA01345 <400> cataacctca ttgaacatgc aaaactaatg cttttggggg gtatgcataa attcgtttcg ttccactgca cagcccgaaa atgctgctag ggtcaagttc atg cgt ttt Met Arg Phe gga ctt Gly Leu gac Asp tat Tyr att Ile ga t Asp aaa Lys t tg Leu gga Gly atc Ile t ct Ser att Ile cta Leu ga t Asp acc Th r act Thr gt g Val qtt Val tct Se r gta Val1 cgc Arg gtg Val gcc Ala ggg Gi y ga a Giu 75 cac His a ca Thr gaa Glu ctc Leu cag Gin ccc Pro cct Pro atc Ile ga t Asp aag Lys 45 gac Asp aa t Asn t tg Leu gcg Ala tct Ser gca Al a cac His gtc Val Gly 1 gtg Val gac Asp att Ile ttc Phe gcc Ala ctg Leu gac cgc Asp Arg acc cac Thr His 3-9 gtc gcg Val Ala 50 gta cgt Val Arg acc ccg Thr Pro gag gct Giu Ala gga Gi y 20 gat Asp ggt Gly t ct Ser gt c Val ttt Phe 100 aac Asn t tc Phe t gg Trp ttc Phe tac Tyr gcg Al a gaa aac gtg gtc Glu Asn Val Val 105 act gcg ctg cgt gca ttt cag acg caa ttg Thr Ala Leu Arg Aia Phe Gin Thr Gin Leu gga gat Gly Asp WO 01/00804 WO 0100804PCT/IBOO/00922 aec tee ccg ate ga a Thr gce Ala gtt Val1 150 cac His tat Tyr ggc Gly ggc Gly ggc Giy 230 ga c Asp ttg Leu ttc Phe gaa Glu atc Ile 310 Se z ca C Gir 135 gtc ValI cgc Arg ga t Asp acc Thr ga t Asp 215 aga Arg gaa Giu gtt Val tac Tyr cc C Pro 295 tao Tyr Pro 120 cga Arg ggt *Gly cac His ttg *Leu cac His 200 ga t Asp cag Gin t cc Ser ct a Leu gag Giu 280 etc Leu ctt Leu Ile Glu gta gtc att Val Val Ile ggt gtg Gly Val ccc gcc aac tcc cac age Pro Ala Asn Ser His Ser 130 125 ctg Leu ttg Leu gc Al a gga GI y 185 ca 0 His ttc Phe eac His cgc Arg ga a Giu 265 gct Ala atc Ile gt t Val1 Ictc Let gtc Val cgc Arg 170 Gly gag Gi u ga t Asp gat Asp aac As n 250 at t Ile gcc Ala 9gc Gly ggt GI y ac Thr aat Asn 155 acc IThr gga Gly gt t Val gaa Glu geg Al a 235 gcg Ala ggc Gly act Thr gtc Val gga Giy 315 at C Met 140 gag Glu tta Leu aca Thr gt g Val1 at c Ile 220 ttt Phe aag Lys gae Asp ccc Pro ga t ksp 300 Iga fly tee Ser ccc IPro aac As n ttc Phe tee Ser 205 etc Leu ggc Gi y ga a Glu gac Asp.
ctg Leu 285 gat Asp tc Ser gcc Ala ag c Se r tcc Ser gac Asp 190 tee Ser etc Leu aa g Lys get Ala gac Asp 270 gt g Val1 -tt Le u tcg Ser ttc Phe gee *Ala aag *Lys 175 tcc Ser att Ile eaa Gin egi Arg ct t Leu 255 ate Ile ga a Giu aaa Lys etc Leu age Ser qca Ala 160 ege Arg tog Se r gge Gi y t ge Cys get Al a 240 gtt Val aee Thr aaa Lys gat Asp cca Pro 320 gee Ala 145 get Ala ca a Gln etc Leu ati Ile geg Ala 225 aaa Lys eeg Pro gt t Val1 tee Ser tee S er 305 etc Leu aea Thr tte Phe gee Al a ate Ile tea Ser 210 etc Leu aac As n caa Gin eea Pro ttg Leu 290 gac Asp gt t Val1 gge Gly gag Glu ate Ile ego Arg 195 ego Arg aag Lys acg Thr tee Ser gtg Val 275 tee Ser ate Ile tee Ser ate Ile tao Tyr gtg Val1 180 ate Ile Ott Leu gee Ala Ct t Leu cgjt Arg 260 aac As n ate Ile gea Al a agg Arg ac Thr ace Thr 165 gt t ValI gac Asp ggt Giy gea Al a etc Leu 245 ege Arg aag Lys atg Met ggc Gly t tg Leu 325 547 595 643 691 739 787 835 883 931 979 1027 1075 1123 etc cgc gag cgt tte ggc ege cgt gte eac ege too cca ttc eec tea Leu Arg Glu Arg Phe Gly 330 Arg Arg Val Arg Ser Pro Phe Pro Ser 340 WO 01/00804 ggt tcc act gcg gtq ggt ctg gce atc Gly Ser Thr Ala Val Gly Leu Ala Ile 345 35C ttc cac eta agg gac cge gtt gcg cga Phe His Leu Arg Asp Arg Val Ala Arg 360 365 cac gat tct ggt cgt gee gtg agc ttt His Asp Ser Gly Arg Ala Val Ser Phe 375 380 <210> 26 <211> 389 <212> PRT <213> Corynebacterium glutamicum <400> 26 Met Arg Phe Gly Leu Asp Leu Gly Thr gcg get gac ect tee tct ggt Ala Ala Asp Pro Ser Ser Gly 355 ggc ate ggt qtg ttc cgt gag Gly Ile Gly Val Phe Arg Giu 370 gac ceg ctg ate gcc ccg gae Asp Pro Leu Ile Ala Pro Asp 385 PCTIIBOO/00922 1171 1219 1267 1 Val1 Asp Ile Phe Ala Leu Thr Ala Ala 145 Ala Gin Asp Thr Vali Val1 Thr Giu Gin Asn 130 Thr Phe Al a Arg His Ala Arg Pro Ala Leu 115 Ser Gi y Gi u Ile Gi y Asp Gly Ser Val1 Phe 100 Gly His Ile Tyr Val 180 5 Asn Phe T rp Phe Tyr Aila Asp Ser Thr Thr 165 Val1 Tyr Ile Asp Lys Leu Giu Th r Ala Val1 150 His Tyr Pro Pro Al a 55 Arg Gly Asn Ser Gin 135 Val1 Arg Asp Ile Ser 40 Ile Leu Asp Val1 Pro 120 Arg Gly His Leu Thr Th r Val Val1 Ser Val1 Thr Glu Leu Val Arg 170 Gly Thr Glu Leu Gin Pro Pro Leu Val1 Met 140 Giu Leu Thr Ile Asp Lys Asp Asn Leu Arg Ile 125 Ser Pro Asn Phe Leu Ilie Arg 195 Ilie Asp Gly Thr His His Giu Val Val Ser Ser Ile Gly 200 205 WO 01/00804 WO 0100804PCT/IBOO/00922 Ile Ser 210 Ala Leu 225 Lys Asn Pro Gin Val Pro Ser Leu 290 Ser Asp 305 Leu Val Ser Pro Asp Pro Giy Val 370 Leu Ala Leu Arg 260 As n Ile Al a Arg Pro 340 Ser Arg Gly Al a Leu 245 Ar g Lys Met Gly Leu 325 Ser Gly Glu Gly Asp 215 Gly Arg 230 Asp Glu Leu Val Phe Tyr Giu Pro 295 Ile Tyr 310 Leu Arg Gly Ser Phe His His Asp 375 Asp Phe Gin His Ser Arg Leu Giu 265 Glu Ala 280 Leu Ile Leu Val Giu Arg Thr Ala 345 Leu Arg 360 Ser Gly Ile 220 Phe Lys Asp Pro Asp 300 Gi y Arg Leu Val Val 380 Leu .Gln Lys Arg Ala Leu 255 Asp Ile 270 Val Glu Leu Lys Ser Leu Val His 335 Ile Ala 350 Arg Gly Phe Asp Leu Ile Ala Pro Asp 385 <210> 27 <211> 1308 <212> DNA <213> Corynebacterium giutamicun <220> <221> CDS <222> (1285) <223> RXA02541 <400> 27 atccgccggt qtccggacaa caaaacttgc aacacaagat aacttaagaa attgcataca attcaccgca tataagactc atggaaggaq gggatgccca gtg aac aac agc gaa 115 Val Asn Asn Ser Glu 1 tgg gca aat aag aac tat tac 9ca qac ctg ggg gtc tcc tcg tcc gct 163 Trp Ala Asn Lys Asn Tyr Tyr Ala Asp Leu Giy Val Ser Ser Ser Ala WO 01/00804 PTIO/02 PCT/IBOO/00922 tea gaa Ser Glu cac eca His Pro aaa gcg Lys Ala gaa tac Glu Tyr gga tte Gly Phe acg gga Thr Gly 000 ttt Gly Phe aac cgc Asn Arg 135 gat gta Asp Val 150 acg ace Thr Thr cac gga His Gly gat gga Asp Gly get cca Ala Pro 215 gat Asp gat Asp gcc Al a ga C Asp gga Gly gga Gly t Ser 120 ggc Gly c aa Gin atc Ile t eg Se r acc Th r 200 tot Cys gag Glu aaa Lys gag Glu gag Glu agc Ser ttC Phe 105 a cg Thr get Ala ace: Thr cca Pro gge Gly 185 gga Gly gca Ala atc Ile aat Asn gca Al a etc Leu gga Gly ga C Asp gac Asp ggt Gly gaa Glu gtg ValI 170 tee Ser ttC Phe acc Thr aaa Lys cca Pro tat Tyr aaa Lys 75 ggt Gly ace Thr gge Gl y tet Se r ata Ile 155 gaa Giu a aa Lys ace: rhr Lgt aag Lys gt Gly gac Asp 60 gca Ala geg Al a tca Se r gg t Gly eac His 140 act Thr etc Leu tea Ser tct Se r got Gly 220 gct Ala gac Asp 45 gta Val1 ct t Leu gga Gly gac Asp t to Leu 125 eag Gln etc Leu ace Thr goC Gi y gag Glu 205 gge Gly tac Tyr aag Lys ctt Leu cta Leu t te Phe etc Leu 110 oge Gly tea Ser t Co Ser gge Gly cac His 190 aae Asn act Thr ege Arg
C
Ala gt Gly gct Ala ec Pro 95 tte Phe gat Asp get Al a ttt Phe gat Asp 175 ccc Pro aag Lys ggt Gl y a ag Lys get Ala gat Asp tct Ser 9gC Gi y gga Gly ate Ile agg Arg gtt Val 160 geg Ala gca Al a got Gly gaa Glu etc Leu gaa GI u oa C Asp got Gly 000 Gly gga Gly t te Phe ceo Pro 145 gag Glu c Pro aaa Lys get Ala ata Ile 225 gee Ala gat Asp a ag Lys Gly t tt Phe gga Gly ggt Gly 130 acg Thr gea Al a toe Cys tgt Cys tte Phe 210 ate Ile gaa Glu ttc Phe coa Arg ege Arg aco Thr 100 ggt Gly ctt Leu 000 Gly aaa Lys ace: Thr 180 ace Thr tt C Phe gat Asp 211 259 307 355 403 451 499 547 595 643 691 739 787 tge gat aae tge cac gge Cys Asp Asn Cys His Gly 230 235 ega gge ace Aro Gly Thr gte Val egg aao tct cgt tce ate Arg Lys Ser Arg Ser Ile 240 245 WO 01/00804 acc Thr gca Ala ttt Phe agc Se r gt GI y 310 ct a Leu ggt Gly gt t Val1 gca Ala cgt Arg ca a Gin aaa Lys 280 att Ile qct Ala gcg Ala gaa Glu gt C Val1 360 gct Al a atC cca act ggt gtg gaa gat Ile Pro Thr Gly Val Glu Asp 250 255 ggc qaa qca qga cca aat ggc Gly Glu Ala Gly Pro Asn Gly 265 270 gtc cac gtg aaa aag gac gat Val His Val Lys Lys Asp Asp 285 ttg atc acc att ccc gtg agc Leu Ile Thr Ile Pro Val Ser 300 att tct gtg cca acg ctc aac Ile Ser Val Pro Thr Leo Asn 315 gga. acg cca gat ggt cgt act Gly Thr Pro Asp Gly Arg Thr 330 335 gca cgt gat tcc act ggt gat Ala Arg Asp Ser Thr Gly Asp 345 350 ccg aag aat ctg gat gac aac Pro Lys Asn Leu Asp Asp Asn 365 gaa gca gaa act aat tca ggt Glu Ala Giu Thr Asn Ser Gly 380 gga cag aaa gtt Gly Gin Lys Val cgt ctt Arg Leu 260 aaa cca Lys Pro gtg ttc Val Phe ttc agc Phe Ser 305 aag cct Lys Pro 320 ttg cgt Leo Arg ctg ctg Leu Leu gCt gcg Ala Ala ttt gat Phe Asp 385 gcg ggc Ala Gly 275 aca cgc Thr Arg 290 gag ctg Glu Leo gta aaa Val Lys gta cgc Vai Arg gtt aca Val Thr 355 gaa gct Glu Ala 370 ccc cgc Pro Arg PCT/IBOO/00922 883 931 979 1027 1075 1123 1171 1219 1267 tgg gcg ggc Trp Aia Gly 390 cag aac cgc tagacgttct ctttgagaaa gga Gin Asn Arg 395 1308 <210> 28 <211> 395 <212> PRT <213> Corynebacteriom glutamicom <400> 28 Val Asn Asn Ser Glu Trp Ala Asn Lys Asn Tyr Tyr Ala Asp Leo Gly 1 5 10 Val Ser Ser Ser Ala Ser Glu Asp Glu Ile Lys Lys Ala Tyr A-rg Lys 25 Leo Ala Arg Glu Asn His Pro Asp Lys Asn Pro Gly Asp Lys Ala Ala 40 WO 01/00804 WO 0100804PCT/IBOO/00922 Giu Asp Asp Lys Giy Gly Gly Phe Gly Gly Phe Gly 130 Pro Thr 145 Glu Ala Pro Cys Lys Cys Ala Phe 210 Ile Ile 225 Lys Ser Gin Lys Pro Ala Phe Thr 290 Ser Glu 305 Pro Val Arq Phe Lys Lys Ala Ala Glu Ala Tyr Arg Lys Arg Gly Thr Ser 100 Gly Giy Leu Phe Giy Ala Lys Gly 165 Thr Cys 160 Thr Cys Phe Ser Asp Pro Ser Ilie 245 Arg Leu 260 Asp Leu Asp Gly Ala Leu Leu Lys 325 Giu 70 Gly Thr Gly Asn Asp 150 Thr His Asp Ala Cys 230 Thr Ala Phe Se r Giy 310 Leu 55 Tyr Phe Gly Phe Arg 135 ValI Thr Gly Gly Pro 215 Asp Val1 Gl y Val1 Asn 295 Gly Pro Asp di y Gly Se r 120 Giy Gin Ile Ser Thr 200 Cys Asn Arg Gin Lys 280 Ile Ala Ala Glu Leu Ser Gly 90 Phe Asp 105 Thr Asp -Ala Gly Thr Giu Pro Val 170 Gly Ser 185 Gly Phe Ala Thr Cys His Ile Pro 250 Gly Glu 265 Val His Leu Ile Ilie Ser Gly Thr 330 Lys Gly Thr Gly Ser Ile 155 Giu Lys Thr Cys Gly 235 Thr Al a Val1 Thr ValI 315 Pro Asp Ala Ala Se r Gi y His 140 Thr Leu Ser Ser Gly 220 Arg Gi y Giy Lys Ile 300 Pro Asp Val Leu Gly Asp Leu 125 Gin Leu Thr dl y di u 205 Gly Gly ValI Pro Lys 285 Pro Thr Gly Gly Al a Pro Phe As p Ala Phe Asp 175 Pro Lys Gly Val Asp 255 Gly Asp Ser Asn Thr 335 Arg Val Arg Arg Vl Arg Arg Gly Ile Glu ArAs SrTh Arg Asp Ser Thr Gly Asp Leu 350 WO 01/00804 Leu Val Thr Val Gin Val Ser Val Pro Lys Asn Leu Asp Asp Asn Ala 355 360 365 Ala Giu Ala Leu Arg Ala Tyr Ala Giu Ala Glu Thr Asn Ser Gly Phe 370 375 380 Asp Pro Arg Ala Asn Trp Ala Gly Gin Asn Arg 385 390 395 <210> 29 <211> 777 <212> DNA <213> Corynebacterium giutamicum <220> <221> CDS <222> (754) <223> RXA02542 <400> 29 ccaggctgac gcaqgtgcag aaggcgctgc agatgacaat gttgttgacg ctgaagtt PCT/IBOO/00922 gt cgaagacgac gcagctgaca atggtgagga caagaagtaa gga Gi y ac c Thr ca a Gin c ca Pro gat Asp gaa Glu cgt Arg
CCC
Pro gCt Ala gag Giu ct C Leu gat Asp act Thr cgt Arg gac Asp ga t Asp gaa Glu gaa Giu Gly gag Glu acc Thr 105 9gg Gly gag Glu ttt Phe atc Ile gaa Giu cag Gin gaa Glu gat cCt Asp Pro cag qca Gin Ala 30 gga cag Gly Gin 45 aat gat Asn Asp gtg tcc Val Ser cga gtc Arg Val cgc cag Arg Gin 110 gaa Glu gct Ala gcc Al a ct t Leu gct Ala acc Thr 9gC Gly aat Asn gaa Giu t ca Ser cta Leu gta Val1 80 gct Al a atc Ile atg act acc cct aac 115 Met Thr Thr Pro Asn 1 acc gat cca gag gca 163 Thr Asp Pro Glu Ala qaa gca gct gcc cgc 211 Glu Ala Ala Ala Arg gag gaa gaa att tct 259 Giu Giu Giu Ile Ser tca gat gtt gat cca 307 Ser Asp Val Asp Pro gaa aca cag ctt gcc 355 Giu Thr Gin Leu Ala gag tac gcc aac tac 403 Giu Tyr Ala Asn Tyr 100 atc oac acc aca cac 451 Ile Thr 115 gca ggt qtt Ala Gly Val gtt acc caa ctt ctg ccg ttg ctc Val Thr Gin Leu Leu Pro Leu Leu gac gat ctt gac ctg Asp Asp Leu Asp Leu 499 WO 01/00804 120 PCTIBOOOO922 125 gct gaa cag cac ggt gac ctt aac Ala Glu Gin His Giy Asp Leu Asn 135 140 gao aag ctg atc aac atc ctg ggt Asp Lys Leu Ile Asn Ile Leu Gly 150 155 gag atc ggc gaa gca ttc gat cca Gl~u Ile Gly Glu Ala Phe Asp Pro 170 otc tca oag ggt gat gtc aag gtt Leu Ser Gin Gly Asp Val Lys Val 185 tao cgc otc ggc gac cgc gtc atc Tyr Arg Leu Gly Asp Arg Val Ile 200 205 gat oca gag gag ago tagagagact a~ Asp Pro Glu Giu Ser 215 <210> <211> 218 <212> PRT <213> Corynebacterium giutamioum <400> Met Thr Thr Pro Asn Gly Met Pro I~ 1 5 Thr Asp Pro Glu Ala Thr Ser Ala Glu Ala Ala Ala Arg Gin Ala Glu C 40 Glu Glu Giu Ilie Ser Pro Glu Leu C Ser Asp Val Asp Pro Asp Leu Asp G Giu Thr Gin Leu Ala Glu Arg Thr G Giu Tyr Ala Asn Tyr Arg Arg Arg T 1001 Ile Asp Thr Ala Arg Ala Gly Val V 115 120 gaa ggt cog otg Glu Gly Pro Leu 145 gqa ttg aag gtg Gly Leu Lys Val 160 gag ato cac gaa G1u Ile His Glu 175 ctg gga acg gta Ueu Gly Thr Val 190 cgo acc gca atg Irg Thr Ala Met agtctctta qtg Asn 10 Arg Ser Ala Asp Asp 90 Giu Thr Asp Gin Gi y Asn Val Arg Arg Leu 125 Pro Al a Gin Asp Ser Val Gin 110 Pro Giu Al a Ala Leu Ala Thr Gly Leu WO 01/00804 Asp Asp Leu Asp Leu Ala Glu Gin His Gly Asp 130 135 Leu Lys Ser Leu Ser Asp Lys Leu Ile Asn Ilie 145 150 155 Val Glu Ser Phe Gly Glu Ile Gly Giu Ala Phe 165 170 Glu Ala Val Gin Asp Leu Ser Gin Giy Asp Val 180 185 Val Leu Arg Lys Gly Tyr Arq Leu Gly Asp Arg 195 200 Met Val Leu Ile Gly Asp Pro Glu Glu Ser 210 215 <210> 31 <211> 1977 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> (1954) <223> RXN02543 <400> 31 ctcaatgagg agtttttctt accggcgaaa gtcggtggga gtggacagta ctaaaatcac ctaaaacagg aggcaccatt PCTIIBOO/00922 Leu Asn Giu Giy Pro 140 Leu Gly Gly Leu Lys 160 Asp Pro Glu Ile His 175 Lys Val Leu Gly Thr 190 Val Ile Arq Thr Ala 205 gga Gly ggC Gly tcc Ser gct Ala aag Lys tac ctt gga Leu Gly gta gtt Val Val gca ttc Ala Phe cag gcg Gin Ala atc ggc Ile Gly cag gaa a cc Thr atc Ilie gca Al a gt c Val1 a cc Thr 75 atc aac Asn aac As n aac Asn aac Asn tgg Trp gc t tct Ser gca Ala 30 ggt Gly gtt Val tcc Ser cg t gtt Vai Gly gt t ValI cgc Arg gct Ala 80 ct g agcaagtcaa agCtcaagcc atg gga cgt gca gta Met Gly Arg Ala Val 1 tcc gta ctt gaa ggc Ser Val Leu Glu Gly tca cgc acc acc cct Ser Arg Thr Thr Pro cta gtc ggc cag tcc Leu Val Gly Gln Ser acc att cgc tcc gtc Thr Ile Arg Ser Val atc gat gac aag aac Ile Asp Asp Lys Asn atg aag ctg aag cgc wo 01/00804 WO 0100804PCTJIB00/00922 Tyr Thr Ser GIn Glu Ile Ser Ala Arg Thr Leu Met Lys Leu Lys Arg 95 100 gac Asp gt t Val1 ggt Gly gcg Ala 150 att Ile gag Glu gag Giu gag Glu gCC Al a 230 tee Se r gca Ala ttc Phe aac Asn get Ala cet Pro cag Gin 135 get Al a ct g Leu ate Ile etc Leu a ag Lys 215 ctg Leu tct Se r gac Asp cag Gin cag Gin gaa Glu gca Ala 120 ate Ile gca Al a gta ValI Gly ggt Gly 200 ttc Phe cag Gin tee Se r aag Lys ege Arg 280 gjt t Val1 gca Ala 105 tac Tyr gca Al a ctt Leu t tc Phe gac Asp 185 gge Gly eag Gin cgt Arg cag Gin aac Asn 265 ate Ile gt t ValI tac Tyr ttc Phe gge Gly gea Al a gac Asp 170 ggt Gly ga c Asp tee Ser ct q Leu agt Ser 250 cca Pro ace Th r aag Lys ctg Leu gag Giu cztt Leu t ac Tyr 155 etc Leu gtt ValI gac Asp tee Ser egt Arg 235 gca Ala ctg Leu cag Gin gac Asp ggC Gil, gac Asp aac Asn 140 gge Gi y ggt Gi y gtt ValI tgg Trp aac As n 220 gag Giu aac Asn t te Phe gac Asp gct ii a 300 gag gac Giu Asp 110 tea cag Ser Gin 125 gtt etg *Val Leu ett gag *Leu Giu Gly Gly gag gtt Glu Val 190 gat eag Asp Gin 205 gge att Gly Ile gca get Ala Ala ate aac Ile Asn ttg gat Leu Asp 270 etc ctg Leu Leu 285 gge gtg Gly Val gte ValI ege Arg Cgt Arg aag Lys ace Tb r 175 ege Arg egt Arg gac Asp gag Giu et t Leu 255 gag Giu gee Ala tee Ser act Thr cag Gin att Ile Gly 160 tte Phe gca Ala atc Ile etg Leu aag Lys 240 ect Pro ace Thr egC Arg gtc Val1 ga t Asp ges Al a gt t Val1 145 gag Giu gac Asp ace Thr gtt Val1 ace Thr 225 gea Al a tac Tyr ett Leu ace Th r teg Se r 305 gtt att Val Ile 115 aag gaa Lys Glu gag cca Glu Pro gag eag Giu Gin tee etc Ser Leu ggc gat Gly Asp 195 tgg ctg Trp Leu gac aag Asp Lys ate gag Ile Giu ace gtt Thr Val 260 egt gee Arg Ala 275 act cet Thr Pro ate gac Ile Asp ace Thr get Ala ace Thr ace Tb r 165 eta Leu aac Asn gt a Val1 atg Met etg Leu 245 gat Asp gag Giu ttc Phe ca c His 451 499 547 595 643 691 739 787 835 883 931 979 1027 1075 295 gtt gtt etc gte Val Val Leu Val ggt ggt Gly Gly tee ace egt atg cet Ser Thr Arg Met Pro get gtt ace gaa etg Ala Val Thr Glu Leu WO 01/00804 PCTIIBOO/00922 aag Lys gag Glu gag Glu att Ile 375 ace Thr cag Gin ace Thr gca Ala aac Asn 455 aac Asn gat Asp ege Arg cag Gin gaa Glu gtt Val gtC Vai 360 gag Glu ate Ile cct Pro gce Ala cca Pro 440 gge Gly ace Thr cgc Arg cgc Arg ace Thr 520 ctg Leu gtt Val 345 aag Lys ace Thr ect Pro tct Ser aae Asn 425 cgt Arg ate Ile ate Ile atg Met gag Glu 505 ege Arg ace Thr 330 gca Ala gat Asp aag Lys acc Thr gtt Val 410 aag Lys ggc Gly gte Val acc Thr atc Ile 490 gag Glu aag Lys ggt Gly gtt Va1 gtt Val ggt Gly aag Lys 395 cag Gin ctg Leu gte Val cac His att Ile 475 aag Lys cag Gin ttc Phe gga Gly ggt Gly ctt Leu ggC Gly 380 cgt Arg atc Ile etc Leu cca Pro gte Val 460 cag Gin gat Asp gaa Glu gtt Val egt Arg gca Ala ctt Leu 365 gtg Val tee Ser cag Gin gga Gly cag Gin 445 ace Thr gac Asp get Ala gte Val gaa Glu 525 cca Pro 335 ctt Leu gac Asp ace Thr ace Thr ttc Phe 415 tte Phe gag Glu aag Lys tee Ser get Ala 495 aac Asn aac Asn aag Lys gec Ala acc Thr etc Leu 385 ace Thr ggc Gly etc Leu act Thr aag Lys 465 etc Leu get Ala get Ala gag Glu 1123 1171 1219 1267 1315 i363 1411 1459 1507 1555 1603 1651 1699 1747 etc aag gca aag gte gaa gag gca Leu Lys Ala Lys Vai Giu Giu Ala gee aag ggc Ala Lys Gly 545 gtt gaa gaa gca Val Giu Glu Ala WO 01/00804 ctc aag ggc gag gac ctc gag gca atc aag gct gca Leu Lys Gly Giu Asp Leu Glu Ala Ilie Lys Ala Ala 550 555 560 aac acc gag tcc cag gaa atg ggt aag gct atc tac Asn Thr Giu Ser Gin Glu Met Gly Lys Ala Ile Tyr 570 575 gct gct ggt gca acc cag gct gac gca ggt gca gaa Ala Ala Gly Ala Thr Gin Ala Asp Ala Gly Ala Giu 585 590 gac aat gtt gtt gac got gaa gtt gtc gaa gac gac Asp Asn Val Val Asp Ala Glu Val Val Glu Asp Asp 600 605.
ggt gag gao aag aag taaatgacta cccctaacqg aat Gly Giu Asp Lys Lys 615 <210> 32 <211> 618 <212> PRT <213> Corynebacterium glutamicum gtt gag aag ctg Val Glu Lys Leu 565 gag gct. gac got Giu Ala Asp Ala 580 ggc gct gca gat Gly Ala Ala Asp 595 gca got gac aat Ala Ala Asp Asn 610 PCTIIBOO/00922 1795 1843 1891 1939 1977 <400> 32 Met Gly Arg Ala Val Gly Ile Asp Leu 1 Ser Val Ser Arg Leu Val Thr Ile Ile Asp Met Lys Asp Ala Ala Thr 130 Leu Thr Gly Arg Asp Leu Val1 115 Lys 5 Gly Gly Pro Ser Ser Ala Val Lys Asn Tyr Arg Asp Thr Val Ala Gly Glu Val1 Lys Arg Thr Ala Pro Gin Pro ValI Asri His Ser Glu Ala 120 Ile Gly Val1 Phe Ala Gly GI u Tyr Phe Gly Thr Thr Asn Ser 135 140 Asn Glu Pro Thr Asn Gu Pr Thr Ala Ala Leu Ala Tyr 155 Gly Leu Glu Lys WO 01/00804 WO 0100804PCT/IBOO/00922 Giu Gin Glu Gin Thr Ile Leu Val Phe Asp Val Thr Ser Val Asp 210 Thr Lys 225 Ala Lys Tyr Ile Leu Ser Thr Lys 290 Ser Giu 305 Aia Vai Lys Giy Ala Gly Thr Pro 370 Leu Ile 385 Thr Thr Gly Glu Leu Gly Thr Phe 450 Ser Gi y 195 Trp Asp Ile Thr Arg 275 Thr Ilie Thr Val1 Val 355 Leu Giu Aia Arg Gly 435 Asp Leu 180 Asp Leu Lys Giu Val1 260 Al a Pro Asp Giu Asn 340 Leu Se r Arg Giu Glu 420 Ile Ile 165 Leu Asn Val Met Leu 245 Asp Giu Phe His Leu 325 Pro Arg Leu As n Asp 405 Ile Ala Asp Giu Giu Giu Ala 230 Ser Ala Phe Asn Val1 310 Val1 Asp Gi y Gi y Thr 390 Asn Aia Pro Al a Ile Leu Lys 215 Leu Ser Asp Gin Gin 295 Val1 Lys Glu Giu Ile 375 Thr Gin Thr Ala Asn 455 Gi y Gly 200 Phe Gin Se r Lys Arg 280 Val Leu Giu Val Val 360 Giu Ile Pro Ala Pro 440 Gly Asp 170 Giy Asp Ser Leu Ser 250 Pro Thr Lys Gly Thr 330 Al a Asp Lys Thr Val1 410 Lys Gi y ValI Leu Giy Gly Gly Val Val Asp Trp Ser Asn 220 Arq Giu 235 Ala Asn Leu Phe Gin Asp Asp Ala 300 Gly Ser 315 Gly Gly Val Gly Val Leu Giy Gly 380 Lys Arg 395 Gin Ile Leu Leu Val Pro His Val 460 Giu Asp 205 Giy Ala Ile Leu Leu 285 Gly Thr Arg Ala Leu 365 Val1 Se r Gin Gly Gin 445 Thr Thr 175 Arg Arg Asp Glu Le u 255 Giu Ala Se r Met Pro 335 Leu Asp Thr Thr Phe 415 Phe Giu Lys WO 01/00804 PCT/IBOO/00922 Lys Giy Thr Gly Lys Gin Asn Thr Ile Thr Ilie Gin Asp Gly Ser Gly 465 470 475 480 Leu Ser Gin Asp Giu Ile Asp Arg Met Ile Lys Asp Ala Gin Ala His 485 490 495 Ala Asp Gin Asp Lys Lys Arg Arg Giu Giu Gin Gin Val Arg Asn Asn 500 505 510 Ala Gin Ser Leu Val Tyr Gin Thr Arg Lys Phe Val Glu Giu Asn Ser 515 520 525 Gin Lys Val Ser Giu Asp Len Lys Ala Lys Val Giu Giu Ala Ala Lys 530 535 540 Gly Val Glu Giu Ala Leu Lys Gly Giu Asp Leu Gin Ala Ile Lys Aia 545 550 555 560 Ala Val Giu Lys Leu Asn Thr Giu Ser Gin Gin Met Giy Lys Ala Ile 565 570 575 Tyr Giu Ala Asp Ala Ala Ala Gly Ala Thr Gin Alac Asp Ala Gly Ala 580 585 590 Gin Gly Ala Ala Asp Asp Asn Val Val Asp Ala Giu Val Val Giu Asp 595 600 605 Asp Ala Ala Asp Asn Giy Giu Asp Lys Lys 610 615 <210> 33 <211> 1977 <212> DNA <213> Corynebacterium gintamicum <220> <221> CDS <222> (1954) <223> FRXA02543 <400> 33 ctcaatgagg agtttttctt accggcqaaa gtcggtggga aqcaagtcaa agctcaagcc gtggacagta ctaaaatcac ctaaaacagq aggcaccatt atg gga cgt gca gta 115 Met Gly Arg Ala Val 1 gga att. gac cit gga acc acc aac tct. gig gtt tcc gta ctt gaa ggc 163 Gly Ilie Asp Len Gly Thr Thr Asn Ser Val Val Ser Val Leu Gin Gly 15 ggc gag cca gta gtt atc gca aac gca gaa ggc tca cgc acc acc cct 211 Gly Glu Pro Val Val Ile Ala Asn Ala Gin Gly Ser Arg Thr Thr Pro 30 WO 01/00804 WO 0100804PCT/IBOO/00922 tcc gtc gtt gca ttc Ser Val gci aag Ala Lys aag cgc Lys Arg tac acc Tyr Thr gac gct Asp Ala git cct Val Pro ggt cag Gly Gin 135 gcg gct Ala Ala 150 ait ctg Ilie Leu gag atc Giu Ile gag ctc Giu Leu gag aag Giu Lys 215 gcc ctg Ala Leu 230 tcc ici Ser Ser Val Ala aac cag Asn Gin cac atc His Ile tca cag Ser Gin gaa gca Glu Aia 105 gca tac Ala Tyr 120 atc gca Ile Ala gca ctt Ala Leu gta tic Vai Phe ggc gac Gly Asp 185 ggt ggc Gly Giy 200 tic cag Phe Gin cag cgt Gin Arg icc cag Ser Gin Phe gcg Al a gg C Gi y gaa Giu tac Tyr tic Phe ggC Gly gca Ala gac Asp 170 ggt Gly ga c Asp icc Ser ctg Leu a gt Ser gca Ala gt c Val acc Thr atc Ile ci g Leu gag Giu ct Leu tac Tyr 155 ctc Leu gt t Val1 ga c Asp tcc Ser cgt Arg 235 gca Ala aag Lys a cc Thr 60 gac Asp t cg Ser ggc Gly ga c Asp a ac As n 140 9gc Gly ggt Gly gtt Val1 igg Trp aac Asn 220 gag Giu aac Asn aac ggt Asn Gly aac gt Asn Val tgg tcc Trp Ser gct cgt Ala Arg gag gac Giu Asp 110 tca cag Ser Gin 125 gtt cig Val Leu ctt gag Leu Giu Gly Gly gag gt Glu Val 190 gat cag Asp Gin 205 ggc ati Gly Ilie gca gci.
Ala Ala atc aac Ile Asn gaa Giu gac Asp gtt Val1 acc Thr gic Val1 cgc Arg cgt Arg aag Lys acc Thr 175 cgc Arg cgt Arg gac Asp gag Giu ct Leu cta Leu acc Thr atc Ile atg Met gati Asp gca Ala gt t Val1 145 gag Giu gac Asp acc Thr gtt Val1 acc Thr 225 gca Al a tac Tyr 250 255 260 gca gac aag aac cca. ctg itc tig gat gag acc ctt tcc cgi gcc gag WO 01/00804 WO 0100804PCT/IBOO/00922 Ala Asp Lys Asn Pro Len Phe Len ttc Phe aac As n gtt Val1 310 gt c Val1 ga t Asp ggc Gly ggc Gi y acc Thr 390 aac Asn gca Ala cct Pro gcc Al a gaa Glu 470 cag Gin cag Gin 295 gt t Val1 aag Lys gag Gin gag Gin att Ile 375 ace Th r cag Gin ace Thr gca Al a aac Asn 455 aac As n cgc Arg 280 gt t Val1 ct C Leu gaa Gin gtt Val1 gtc Val1 360 gag Giu ate Ilie ct Pro gcc Ala c ca Pro 440 ggc Gi y ace Th r 265 ate Ile gt t ValI gtc Val1 ctg Len gtt Val1 345 aag Lys ace Th r ect Pro t ct Ser aac Asn 425 cg t Arg ate I le atc Ile acc Thr aag Lys ggt Gly ace Thr 330 gea Al a gat Asp aag Lys ace Thr gtt Val1 410 aag Lys ggc Gly gtc ValI ace Thr cag Gin gac Asp ggt Gi y 315 qgt Gi y gt t ValI gt t Val ggt Gly aag Lys 395 cag Gin etg Leu gte Val cac His at t Ile 475 ga c Asp get Ala 300 tee Ser gga Gly ggt G ly Ct t Leu ggc Gi y 380 eq t Arg ate Ile etc Leu eca Pro gte Val 460 eag Gin etc Leu 285 gge Gly ace Thr egt Arg gca Al a ctt Leu 365 gtg Val tee Ser cag Gin gga Gly cag Gin 445 ace rhr gae Asp Asp 270 ctg Leu gtg Val1 egt Arg gag Gin gca Ala 350 ctt Len atg Met gag Gin gte Val1 tee Ser 430 ate Ile gca Ala ggc Gly Gin Thr Leu Ser Arg Ala Giu 275 gee Al a tee Se r atg Met eca Pro 335 ett Len gac Asp ace Thr ace Thr ttc Phe 415 ttc Phe gag Gin aag Lys tc Ser ege Arg gt c ValI cct Pro 320 aac Asn eag Gin gte Val1 aag Lys ttc Phe 400 eag Gin gag Gin gte Val gac Asp ggt Gly 480 ace aag Thr Lys 290 tcg gag Ser Giu 305 get gtt Ala Val aag ggt Lys Gly gee ggt Ala Gly ace cea Thr Pro 370 etc ate Leu Ile 385 ace ace Thr Thr ggc gag Gly Gin etc ggc Len Gly act ttc Thr Phe 450 aag ggt Lys Gly 465 etc tee Leu Ser ect ttc Pro Phe gae eac Asp His gaa etg Gin Leu 325 aae eca Asn Pro 340 etc ege Len Arg tee etc Ser Len cge aac Arg Asn gag gac Gin Asp 405 gaa ate Gin Ile 420 ate gea Ile Ala ate qac Ile Asp gge aag Gly Lys gat gaa Asp Gin 485 979 1027 1075 1123 1171 1219 1267 1315 1363 1411 1459 1507 1555 1603 att gat Ile Asp ege atg ate aag gat get gaa get cac get gat gag gac aag Arg Met Ile Lys Asp Ala Gin Ala His Ala Asp Glu Asp Lys WO 01/00804 WO 0100804PCT/IBOO/00922 aag ege cgc gag gag eag gaa gte egc aac aac get Lys Arg Arg Giu GIlu Gin Glu Val Arg Asn Asn Ala 505 510 tac cag ace cgc aag ttc gtt gaa gag aac tee gag Tyr Gin Thr Arg Lys Phe Val Glu Glu Asn Ser Glu 520 525 gac ctc aag gca aag gte qaa gag gea gee aag ggc Asp Leu Lys Ala Lys Val Glu Glu Ala Ala Lys Gly 535 540 545 ctc aag ggc gag gac etc gag gca atc aag qet gea Leu Lys Gly Giu Asp Leu Giu Ala Ile Lys Ala Ala 550 555 560 aac ace gag tee cag qaa atg ggt aag gnt ate tnc Asn Thr Glu Ser Gin Glu Met Gly Lys Xaa Ilie Xaa 570 575 net get ggt gea ace cag get gac gca ggt gea gaa Xaa Ala Gly Ala Thr Gin Ala Asp Ala Gly Ala Glu 585 590 gac aat gtt gtt gae get gaa gtt gte gaa gac gac Asp Asn Val Val Asp Ala Giu Val Val Giu Asp Asp 600 605 ggt gag gae aag aag taaatgacta eeeetaaegg aat Giy Giu Asp Lys Lys 615 <210> 34 <211> 618 <212> PRT <213> Corynebacterium glutamicum <400> 34 Met Giy Arg Ala Val Gly Ile Asp Leu Gly Thr Thr 1 5 Ser Val Leu Giu Gly Gly Giu Pro Val Val Ile Ala Ser Arg Thr Thr Pro Ser Val Vai Ala Phe Ala Lys Leu Val Gly Gin Ser Ala Lys Asn Gin Ala Val Thr 55 Thr Ilie Arg Ser Val Lys Arg His Ile Gly Thr Asp 70 Ile Asp Asp Lys Asn Tyr Thr Ser Gin Glu Ile Ser 1651 1699 1747 1795 1843 1891 1939 1977 WO 01/00804 90 Met Lys Leu Lys Arg Asp Ala Glu Ala Tyr Leu Gly Giu Asp Val Thr 100 105 110 Asp Ala Val Ile Thr Val Pro Ala Tyr Phe Glu Asp Ser Gin Arg Gin 115 120 125 Ala Thr Lys Glu Ala Gly Gin Ile Ala Giy Leu Asn Val Leu Arg Ile 130 135 140 Val Asn Giu Pro Thr Ala Ala Ala Leu Ala Tyr Gly Leu Glu Lys Gly 145 150 155 160 Glu Gin Glu Gln Thr Ile Leu Val Phe Asp Leu Gly Gly Gly Thr Phe 165 170 175 Asp Val Ser Leu Leu Giu Ile Gly Asp G].y Val Val Giu Val Arg Ala 180 185 190 Thr Ser Gly Asp Asn Glu Leu Gly Gly Asp Asp Trp Asp Gin Arg Ile 195 200 205 Val Asp Trp Leu Val Giu Lys Phe Gin Ser Ser Asn Gly Ile Asp Leu 210 215 220 Thr Lys Asp Lys Met Ala Leu Gin Arg Leu Arg Giu Ala Ala Glu Lys 225 230 235 240 Ala Lys Ile Giu Leu Ser Ser Ser Gin Ser Ala Asn Ile Asn Leu Pro 245 250 255 Tyr Ilie Thr Val Asp Ala Asp Lys Asn Pro Leu Phe Leu Asp Giu Thr 260 265 270 Leu Ser Arg Ala Glu Phe Gin Arq Ilie Thr Gin Asp Leu Leu Ala Arg 275 280 285 Thr Lys Thr Pro Phe Asn Gin Val Val Lys Asp Ala Gly Vai Ser Vai 290 295 300 Ser Glu Ile Asp His Val Val Leu Val Gly Giy Ser Thr Arg Met Pro 305 310 315 320 Ala Vai Thr Giu Leu Vai Lys Glu Leu Thr Gly Gly Arg Glu Pro Asn 325 330 335 Lys Gly Val Asn Pro Asp Glu Val Val Ala Val Gly Ala Ala Leu Gin 340 345 350 Ala Giy Val Leu Arg Gly Glu Val Lys Asp Val Leu Leu Leu Asp Val 355 360 365 Thr Pro Leu Ser Leu Gly Ile Giu Thr Lys Gly Gly Val Met Thr Lys 370 375 380 Leu Ilie Glu Arg Asn Thr Thr Ile Pro Thr Lys Arg Ser Giu Thr Phe PCT/IBOO/00922 WO 01/00804 PCT/IBOO/00922 385 390 395 400 Thr Thr Ala Giu Asp Asn Gin Pro Ser Val Gin Ile Gin Val Phe Gin 405 410 415 Gly Giu Arg Giu Ile Ala Thr Ala Asn Lys Leu Leu Gly Ser Phe Giu 420 425 430 Leu Gly Gly Ile Ala Pro Ala Pro Arg Gly Val Pro Gin Ile Glu Val 435 440 445 Thr Phe Asp Ile Asp Ala Asn Gly Ile Val His Val Thr Ala Lys Asp 450 455 460 Lys Gly Thr Gly Lys Giu Asn Thr Ile Th Ile Gin Asp Gly Ser Giy 465 470 475 480 Leu Ser Gin Asp Giu Ilie Asp Arg Met Ile Lys Asp Ala Giu Aia His 485 490 495 Ala Asp Glu Asp Lys Lys Arg Arg Glu Giu Gin Glu Vai Arq Asn Asn 500 505 510 Ala Giu Ser Leu Val Tyr Gin Thr Arg Lys Phe Vai Giu Giu Asn Ser 515 520 525 Giu Lys Val Ser Glu Asp Leu Lys Ala Lys Val Giu Glu Ala Ala Lys 530 535 540 Gly Val Giu Glu Ala Leu Lys Gly Giu Asp Leu Giu Ala Ile Lys Ala 545 550 555 560 Ala Val Glu Lys Leu Asn Thr Glu Ser Gin Giu Met Gly Lys Xaa Ile 565 570 575 Xaa Giu Ala Asp Ala Xaa Ala Gly Ala Thr Gin Ala Asp Ala Gly Ala 580 585 590 Giu Gly Ala Ala Asp Asp Asn Val Val Asp Ala Giu Val Val Glu Asp 595 600 605 Asp Ala Ala Asp Asn Gly Glu Asp Lys Lys 610 615 <210> <211> 1947 <212> DNA <213> Corynebacteriun giutamicum <2 <221> CDS <222> (1924) <223> RXN02280 <400> cgcgattgcg tcatcgatcg ttgttgcttc catgcgcacc acactatctt tctgcacgcc WO 01/00804 ctgatgccct gtggattcaa aactgtgctt PCT/IBOO/00922 115 ttataggcgt caa gaa tee tca t Gin Giu Ser Ser 1 eq t Arg ege Arg aat Asn t ac T yr ttt Phe gaa Glu etg Leu tgt Cys geg Ala gag Glu 150 gt g Val tee Ser ga t Asp cac His geg Ala gag Giu tea Ser ttg Leu ca g Gin tte Phe t cg Ser 135 att Ile eac His gtg Val aa t Asn att Ile gt t Val1 c cg Pro ct g Leu ctg Leu egg Arg atg Met 120 geg Ala ett Leu ct g Leu gte Val tte Phe tat Tyr gat Asp ag t Se r gt t ValI geg Ala gaa Giu 105 gt g ValI at t Ilie ggg Gly act Thr ace Thr 185 eaa Gin tee Ser get Ala att Ile gat Asp a eg Thr ggt Gly geg Ala egg Arg gat Asp ceg Pro 170 att Ile gt t Val1 qgt Gly tgt Cys eq t Arg aat Asn 75 gtg Val cge Arg gat Asp tgg Trp gac Asp 155 ege Arg get Ala ga c Asp cq Pro act Th r at t Ile 60 ggt Gly ggg Gly etg Leu gag Giu act Thr 140 gca Ala ect Pro agt Ser etc Leu agg Arg gca Ala cgg Arg a eq Thr egg Arg ggg Gly ate Ile 125 ggt Gly acg Thr ga t Asp aat Asn ggc Gly gtg Val1 cgt Arg ccg Pro gge Gly aeg Thr ea a Gin 110 ace Thr cat His ga t Asp gag Giu tat Tyr 190 gge Gly tat Tyr tct Ser gt g Val1 ctg Leu teg Ser ttt Phe atg Met geg Ala gte Val1 ege Arg 175 gge Gly gtt Val1 gtg Val1 gaa Giu ace Thr ace Thr 80 aaa Lys ggc Gly gtg Val gat Asp at t Ile 160 acg Thr ege Arg gt t Val1 eg t Arg ca g Gin aag Lys gcg Ala cgc Arg ate Ile t eg Ser ggC Gly 145 ceg Pro t tg Leu t ac Tyr agt Ser eag Gin Gly aeg Thr egg Arg ggt Gly agt Se r gg t Gly etg Leu act Thr 165 aat As n ect Pro gtg att gtg gtg cag ggt gag Ile Val Val Gin Gly Giu no0 aaa aac ace ace ate act aca teg ceg 1ys Asn 205 Thr Thr Ile Thr Ser Pro Val ttt Phe cgc Arg 230 at c -Il e tcc Se r Oct Pro a at Asn gac Asp 310 tog Ser ttt Phe gog Ala cgt Arg gat Asp 390 aac Asn ca c His WO 01/00804 gca. aag gat Ala Lys Asp 215 cit ggt aaa Leu Gly Lys gag ggi gig Giu Gly Val agg cgt cac Arg Arg His 265 tcc aog gtg Ser Thr Val 280 tca. acc gat Ser Thr Asp 295 acc gog ttc Thr Ala Phe tgg otg att Trp Len Ilie act gog att Thr Ala Ile 345 gao otg got Asp Len AlaC 360 ggt cgo atc t Gly Arg Ilie E 375 gtg tog otg c Val Ser Len G acc ait gog c Thr Ile Ala A 4 gao ago gat c Asp Ser Asp L act Thr act Th x got Al a 250 agt Ser otg Leu tt g Leu gog Al a aat Asn 330 cat Hijs ]aa.
1lu ;cg er :ag ;in go ~rg 10 tg eu gat Asp cot -Pro 235 tat Tyr att Slie 000 Pro ga Glu gca Ala 315 oto Leu gat Asp acc Thr a to Ile otg Leu 395 cog Pro got Al a *cag Gin 220 tti Phe gta Val tat Tyr aac Asn 000 Pro 300 a cc Thr 900 Ala ott Leu atg Met ggt Giy 360 got Ala gac Asp ogg C Arg I cac O ir gat Asp tg Leu gtc Val1 t gg Trp 285 a cc Thr agg Arg atg Met gcc Aila t tg Len 365 gag Glu 300 Thr a00 rhr ti .eu cac His gto Val cog Pro aac Asn 270 gog Ala g Os Ala gaa Gin cc Th r ctg Leu 350 ggt Gly ato Ile aog Thr tig Leu att Ile agg Arg atc Ile gag Giu 255 ogo Arg ttc Phe tog Se r cat His a ag Lys 335 ogo Arg Ott Len acc Thr htg Leu tt Ile 415 :00 Pro otg Leu gat Asp 240 gc Ala sig Met ttt Phe og t Arg ato Ile 320 ct Pro gag Gin oto Leu aog Thr gat Asp 400 sti Ile gtt Val tat Tyr 225 ci c Leu cag Gin tig Len gtg Vali gaa Gin 305 ggt Giy cac His otg Leu a cc Thr tt g Len 385 gat Asp sat Asn cac HIis gc Ala a co Thr got Ala gtc Val gaa.
Gin 290 gog Ala gag Gin ogo Arg t go Cys tg Len 370 too Ser ttC Phe ggc Gly tao Tyr ggc Gly ggt Gly oog Pro tot Se r 275 t gt Cys otc Len tgo Cys gtg Vali oa Gin 355 gag Gi u at 0 Ile agg Arg ggc Gly ooa.
Pro ogg Arg oct Pro cat His 260 ga t Asp gaa.
Gin atg Met at Ile Cgg Arg 340 tog Ser sc Th r aco Th r cag Gin tao Tyr 420 cog Pro gag Giu Gi y 245 aig Met ggg Gly aic Ile gat Asp aa Lys 325 gas.
Gin gao Asp too Se r gag Glu oto Len 405 st Ile ct Leu PCTIIBOO/00922 787 835 883 931 979 1027 1075 1123 1171 1219 1267 1315 1363 1411 425 430 435 acg gta tot act got gao ctg ogo gas. too atg gat otg aig gag ott 1459 WO 01/00804 PCT[IBOO/00922 Thr Val Ser Thr Ala Asp Leu Arg Glu Ser Met Asp Leu Met Glu Leu 440 445 450 ccg ccg ctg cag gac att gag aaa gcc aag gca ctg gat gcg cag gtc 1507 Pro Pro Leu Gin Asp Ilie Glu Lys Ala Lys Ala Leu Asp Ala Gin Val 455 460 465 acg qaa tca ttg aag gat ttt cag atc aag ggc gca acg agg gtt ttt 1555 Thr Glu Ser Leu Lys Asp Phe Gin Ile Lys Gly Ala Thr Arg Val Phe 470 475 480 485 gaa ccc gca gat gtt cct gcc gtg gtg atc att gat tcc aag gcg cag 1603 Glu Pro Ala Asp Val Pro Ala Val Val Ile Ile Asp Ser Lys Ala Gin 490 495 500 gcc tca cgg gat cgc aat gaa aca caa agc ges acc act gat cgt tgg 1651 Ala Ser Arg Asp Arg Asn Glu Thr Gin Ser Ala Thr Thr. Asp Arg Trp 505 510 515 gct gac att ttg gca acg gtg gat aac acg ttq agc cgt caa aca gcc 1699 Ala Asp Ile Leu Ala Thr Val Asp Asn Thr Leu Ser Arg Gin Thr Ala 520 525 530 aac att cca cag gat cag gga ctg tcg gcg ttg tgc ttg aat tgg aac 1747 Asn Ilie Pro Gin Asp Gin Gly Leu Ser Ala Leu Cys Leu Asn Trp Asn 535 540 545 aat tcg ctg gtc agg aaa ttg gcg tcc act gat gac acc gcc gtg gtg 1795 Asn Ser Leu Val Arg Lys Leu Ala Ser Thr Asp Asp Thr Ala Val Val 550 555 560 565 tcg cgc acg gtg cgt ttg ctc tac qtt cag gca ttg ttg tcc agc aag 1843 Ser Arg Thr Val Arg Leu Leu Tyr Val Gin Ala Leu Leu Ser Ser Lys 570 575 580 agg cca ctg cgg gtg aag qaa cgc gcg ctg ctt aat gat tcg ctg gca 1891 Arg Pro Leu Arg Val Lys Glu Arg Ala Leu Leu Asn Asp Ser Leu Ala 585 590 595 gat ctg gtt tct ttg tct ttg tca tcc gat atc taagacaatc ctccgctaat 1944 Asp Leu Val Ser Leu Ser Leu Ser Ser Asp Ile 600 605 ctt 1947 <210> 36 (211> 608 <212> PRT <213> Corynebacterium glutamicum <400> 36 Met Gin Glu Ser Ser Arg Asp Asn Phe Gin Val Asp Leu Gly Gly Val 1 5 10 Val Asp Leu Leu Ser Arg His Ile Tyr Ser Gly Pro Arg Val Tyr Val 25 WO 01/00804 W00110804PCT/IBOO/00922 Arg Glu Leu Leu Gin Asn Ala Val Asp Ala Cys Thr Ala Arg Ser Glu Gin Lys Ala Arg Ile Ser Gly 145 Pro Leu Tyr Thr Tyr 225 Leu Gin Leu Val4 Giu 305 Gly Asp Gin Asp Giy His 130 Th r Vali Leu Leu Thr 210 Ala Thr Al a ValI Glu 290 kla Glu Arg Glu Giu Leu 115 Aila Phe Gi y Thr Pro 195 Ser Gi y Giy Pro Ser 275 Cys Leu Giu Al a Ala Phe 100 Leu Glu Asn Thr Giu 180 Ile Pro Arg Pro His 260 A~sp Glu l1et Gi y Thr Arg Gly Ser Gi y Leu Thr 165 Asn Pro Val Glu Gly 245 Met Gly Ile Asp *Tyr *Phe 70 Giu Leu Cys Al a Glu 150 Val Ser Ie Phe Arg 230 Ile Ser Pro Asn Asp 310 Glu 55 Ser Leu Gin Phe Ser 135 Ile His Val3 ValI Al a 215 Leu Glu Arg Ser Se r 295 rhr 40 IPro Leu Leu Arg Met 120 Al a Leu Leu Val1 ValI 200 Lys Gly Gly Arg Thr 280 Thr2 Ala Ser Val1 Ala Glu 105 Val Ile Gly Th r Thr 185 Gin Asp Lys Val1 His 265 ValI ksp he Ile Asp Thr 90 Gly Al a Arg Asp Pro 170 Ile Gly Thr Thr Ala 250 Ser Leu Leu Ala *Arg Asn 75 Val1 Arg Asp Trp Asp 155 Arg Ala Giu Asp Pro 235 Tyr Ile Pro Giu Ala 315 I le Gi y Gly Leu Glu Thr 140 Ala Pro Ser Lys Gin 220 Phe Val1 Tyr Asn Pro 300 Thr Arg Thr Arg Gly Ile 125 Gly Thr Asp Asn Asn 205 Gin Asp Leu Val Trp 285 Thr Arg Pro Gi y Thr Gin 110 Thr His Asp Glu Tyr 190 Thr His Val1 Pro Asn 270 Al a Al a Giu Val1 Leu Ser Phe Met Ala Val Arg 175 Gly Thr Arg Ile Glu 255 Arg Phe Ser His Thr Thr Lys Gly Val Asp Ile 160 Thr Arg Ile Leu Asp 240 Ala Met Phe Arg Ile 320 Gly Giu Cys Ile Lys Ser Trp Leu Ile Asn Leu Ala Met Thr Lys Pro 335 WO 01/00804 WO 0100804PCT/IBOO/00922 His Arg Val Leu Thr Leu 385 Asp Asn His Asp Leu 465 Ala Asp Thr Ser Cys 545 Asp Leu Cys Leu 370 Ser Phe Giy Tyr Leu 450 Asp Thr Ser Thr Arg 530 Leu Th r Leu Gin 355 Giu Ile Arg Gly Pro 435 Met Ala Arg Lys Asp 515 Gin As n Al a Ser Arg 340 Ser Thr Thr Gin Tyr 420 Pro Giu Gin Val Ala 500 Arg Th r Trp Val1 S er Giu Phe Thr Ala Ile His Asp Leu Ala Asp Se r Glu Leu 405 Ile Leu Leu Val1 Phe 485 Gin Trp Ala Asn Val1 565 Lys Al a Arg Asp 390 Asn His Th r Pro Thr 470 Giu Ala Ala As n As n 550 Ser Arg Asp Gly 375 Val Thr Asp ValI Pro 455 Giu Pro Se r Asp Ile 535 Ser Arg Pro Leu 360 Arg Se r Ile Ser S er 440 Leu Se r Ala Arg Ile 520 Pro Leu Thr Leu 345 Al a Ile Leu Ala Asp 425 Thr Gin Leu Asp Asp 505 Leu Gin Vai Val1 Arg 585 Giu Ser Gin Arg 410 Leu Al a Asp Lys Val1 490 Arg Ala Asp Arg Arg 570 Val Thr Ile Leu 395 Pro Ala Asp Ile Asp 475 Pro Asn Thr Gin Lys 555 Leu Lys Met Gi y 380 Al a Asp Arg Leu Giu 460 Phe Ala Glu Val1 Gly 540 Leu Leu Glu Leu 365 G iu Thr Thr Leu Arg 445 Lys Gin Val1 Tb r Asp 525 Leu Ala Tyr Arg Leu 350 Gly Ile Thr Leu Ile 430 Giu Al a Ile Val1 Gin 510 Asn Ser Ser Val1 Ala 590 580 Asn Asp Ser Leu Ala Asp Leu Val Ser Leu Ser Leu Ser Asp Ile <210> 37 WO 01/00804 <211> 436 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> (101) (436) <223> FRXA02282 <400> 37 cgegattgcg tcatcgatcg ttgttgcttc catgcgcacc ctgatgcect gtggattcaa aactgtgctt ttataggcgt PCT/IBOO/00922 egt Arg ege Arg aat Asn tac Tyr ttt Phe gaa Giu ctg Leu aat Asn att Ile gt t Val1 ccg Pro ctg Leu ctg Leu cgg Arg caa Gin tcc Ser gct Ala att Ile gat Asp a cg Thr ggt Gly etc ggc Leu Gly agg gtg Arg Val gca cgt Ala Arg 45 cgg ceg Arg Pro acg ggc Thr Gly cgg acg Arg Thr ggg caa Gly Gin 110 gge Gi y 15 tat Tyr tct Ser gt g Val1 ct g Leu t cg Ser 95 ttt Phe acactatctt tctgcacgcc atg caa gaa tee tea Met Gin Glu Ser Ser 1 gtt gat ett ttg agt Vai Asp Leu Leu Ser egt gag ttg ctg cag Arg Glu Leu Leu Gin eag ggt gag gag gge Gin Gly Giu Glu Gly aag gat eqt gee acg Lys Asp Arg Ala Thr gcg eag gag gcg egg Ala Gin Giu Ala Arg egc gat gaa ttc ggt Arg Asp Glu Phe Gly 100 115 163 211 259 307 355 403 <210> 38 <211> 112 <212> PRT <213> Corynebacterium giutamicum <400> 38 Met Gin Giu Ser Ser Arg Asp Asn Phe Gin Val Asp Leu Gly Gly Val 1 5 10 Vai Asp Leu Leu Ser Arg His Ile Tyr Ser Gly Pro Arg Val Tyr Val 25 WO 01/00804 PCT/IBOO/00922 Arg Glu Leu Leu Gin Asn Ala Val Asp Ala Cys Thr Ala Arg Ser Glu 40 Gin Gly Glu Giu Giy Tyr Glu Pro Ser Ile Arg Ile Arg Pro Val Thr 55 Lys Asp Arg Ala Thr Phe Ser Leu Val Asp Asn Gly Thr Giy Leu Thr 70 75 Ala Gin Giu Ala Arg Glu Leu Leu Ala Thr Val Gly Arg Thr Ser Lys 90 Arg Asp Glu Phe Gly Leu Gin Arg Glu Gly Arg Leu Gly Gin Phe Gly 100 105 110 <210> 39 <211> 1269 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> (1246) <223> RXA00886 <400> 39 taagtatgtt ggtcgtgtgc tcgctggcga atagctgcgg tgattaatct gtttagasgc taaaggaagt atcacccacc ggC Gly gca Al a gag Glu ctc Leu atg Met ggC ggc Gi y sag Lys gcg Ala ccg Pro ggc 61 y ggt gt c Val1 ct t Leu gag Giu ga t Asp ggc Gly ggs ga t Asp gcc Ala aaa Lys sag, Lys 60 gga Gly ct g cgc aat Arg Asn cgc aaa Arg Lys ttC cgc Phe Arg cgc cgc Arg Arg gct ggc Ala Gly ggc gat acc Thr cac His gct Al a gt t Val1 ggt Gly 80 ttc gtatagttgg ccatttgttt gtg gca cgt gac tat Vai Ala Arg Asp Tyr 1 gsa tca gag atc as Glu Ser Giu Ile Lys ccg gac gta sac cca Pro Asp Val Asn Pro tct gtt gcg cat gag Ser Val Ala His Glu gat atg ggc ggt gac Asp Met Gly Giy Asp ggc ttc ggt gga ggc Gly Phe Gly Gly Gly gat gcc ttc ttc ggc 115 163 211 259 307 355 403 WO 01/00804 WO 0100804PCT/IBOO/00922 Phe Gly Gly Ser gg t Gly agt Ser qqc Gly t gt Cys 150 acc Thr 9gC Gi y gag Glu cg t Gly 230 ggt Gly atc Ile atg Met ggc Gly ggc Gly gac Asp gct Ala 135 cat His tgt Cys aac As n atc Ile gct Ala 215 atg Met cct Pro ttc Phe ttc Phe gaa gcg Ala acc Thr 120 aag Lys ggt GI y aat Asn gtc Val1 atc Ile 200 cgc Arg cgc Arg gcg Al a acc Tb r ga t Asp 280 gag Glu ggc Gly 105 ttg Leu aaa Lys tct Ser 9gc Gly atg Met 185 cca Pro cgc Arg atc Ile ggt Gly cgc Arg 265 gca Ala gtg Val G13 gg t Gi11 tgc Trp ga t Asp gga Gly gct Al a 170 acg Thr gat Asp gac Asp cgc Arg qac Asp 250 ga t Asp gcg Ala ~aaa tcc Ser cgc Argq ctc ILeu t ct Ser 155 ggt Gly tcc Ser C ct Pro atc Ile atg Met 235 ct c Leu ggc Gly ctt Leu att Ile cgt Arg acc '1hr acc Thr 140 gca Ala gaa Glu cgc Arg tgc Cys gt g Val1 220 gca Al a t ac Tyr gac Asp 9gC Gly acc rhr *gga Gly tcc *Ser 125 ct t Leu t cc Ser att Ile cca Pro act Th r 205 gcc Al a ggc Gly a tt Ile gat Asp acc Thr 285 atc Ile cca a tc I le gac Asp gac Asp ca g Gin tgc Cys 190 gag Glu aac Asn caa Gin gaa Glu ctg Leu 270 gaa.
Glu cct Pro cgt Arg acc Thr acc Thr aag Lys gaa.
Glu 175 cac His t gt Cys atc Ile ggt Gly gt c Va 1 255 ca c His t tg Leu gca Ala tcc S er ttg Leu gca Al a aag Lys 160 gt g Val acc Thr gca Ala cca.
Pro gag Glu 240 atg Met gcc Ala gac Asp ggt Gly cgc Arg gaa Glu gt g Val 145 cct Pro cag Gln tgc Cys gca Al a gct Ala 225 gt t Val1 gtg Val agc Ser gtg Val act Thr 305 Gly Leu Gly Asp Ile Phe Asp Ala Phe Phe Gly gtg Val1 gag Glu 130 ctg Leu gt t Val cgc Arg gat Asp gat Asp 210 ggC Gly ggc Gly cgc Arg at c Ile ga a Gi u 290 cag Gin 100 cag cca Gin Pro 115 gct tac Ala Tyr tgt acc Cys Thr acc tqt Thr Cys agc ttc Ser Phe 180 ggc acc Gly Thr 195 ggt cgt Gly Arg atc cag Ile Gin gct ggt Ala Gly ccg cac Pro His 260 aag gtt Lys Val 275 tcc ctc Ser Leu ccc aac Pro Asn ggc Gly aag Lys aag Lys 9gc Gly 165 ctg Leu ggt Gly gt g Val1 tcc Ser ggc Gly 245 gcc Ala cca Pro a cc Thr gat Asp 451 499 547 595 643 691 739 787 835 883 931 979 1027 1075 gtg atc acc ttg Val Ilie Thr Leu gat ggt gaa ggc atg ccg aag ctg cgc gca gaa ggC Asp Gly Giu Gly Met Pro Lys Leu Arg Ala Glu Gly WO 01/00804 WO 0106804PCT/IBOO/00922 310 315 cac ggc aac ctc atg gcg cat gtc His Gly Asn Leu Met Ala His Val 330 gat gac cgc acc eye gaa ttg ct Asp Asp Arg Thr Arg Glu Leu Leu 345 gac aac gct tcc gtg cat cgc gaa Asp Asn Ala Ser Val His Arg Glu 360 365 gac aag etc cga aac aag te cgc Asp Lys Leu Arg Asn Lys Phe Arg 375 380 atc <210> <211> 382 <212> PR? <213> Corynebacterium glutamicum <400> Val Ala Arg Asp Tyr Tyr Gly Ile 320 325 gat cta ttt gtg cca acc gat ttq Asp Leu Phe Val Pro Thr Asp Leu 335 340 gaa gaa ate cgc aac cat eye agc Glu Glu Ile Arg Asn His Arg Ser 350 355 ggc gga gaa gaa tcc 9gt ttc ttt Gly Gly Glu Glu Ser Gly Phe Phe 370 aaa taatgtcact gccagtattt Lys 1123 1171 1219 1266 1269 eu Gly Val Asp Arg Asn Ala Thr 1 Glu Pro Se r Asp Gly Asp Arg Glu Val1 145 Glu Val1 Al a Gi y Gly Phe Gin 115 Ala Cys Lys Gly Val1 Pro 70 Phe Gly Ser Gly Cys 150 Ala Glu Leu Met Gly Gly Asp Al a 135 His Tyr Glu Thr Glu Gly Al a Thr 120 Lys Gly 10 Arg Lys Ala Ala Asp Pro Gin Gly Ser Gly Gly Gly 105 Leu Trp Lys Asp Ser Gly Leu Glu Asp Gly Gly Ser Arg Leu Se r 155 Ala Lys Lys Gly Leu Arg Thr Thr 140 Ala Tyr Glu Ile Al a Ile Arg Thr Thr Lys Pro Gin Cys Ala Ala 225 Val Val Se r Val Thr 305 Leu Val Arg WO 01/00804 Val Thr Cys Arq Ser Phe 180 Asp Gly Thr 195 Asp Gly Arg 210 Gly Ile Gin Gly Ala Gly Arq Pro His 260 Ile Lys Val 275 Glu Ser Leu 290 Gin Pro Asn Arg Ala Giu Pro Thr Asp 340 Asn His Arg 355 Gly 165 Leu Gly Val Ser GI y 245 Ala Pro Thr Asp G1y 325 Le u Se r Th r Gly Giu Arg Gly 230 Gi y Ile Met Gly Val 310 His Asp.
Asp Cys Asn Ile Ala 215 Met Pro Phe Phe Glu 295 Ile Gly Asp Pisn As n Val1 Ile 200 Arg Arg Al a Thr Asp 280 Giu Thr Asn Arg Al a Gly Met 185 Pro Arg Ile Gi y Arg 265 Ala Val Leu Leu Thr 345 Ser Ala 170 Thr Asp Asp Arg Asp 250 Asp Ala Lys Asp Met 330 Arg Val GI y Se r Pro Ile Met 235 Leu Gly Leu Ile Giy 315 Al a Glu His Giu Arg Cys Val1 220 Ala Tyr Asp Gi y Thr 300 Giu H is Leu Arg Ile Pro Thr 205 Ala Gly Ile Asp Thr 285 Ile Gly Val Leu Gi u 365 Gin Cys 190 Gi u As n Gin Gi u Leu 270 Glu Pro Met Asp Gi u 350 Giy Vai Thr Ala Pro Glu 240 Met Al a Asp Gly Lys 320 Phe Ile Glu PCT/IBOO/00922 360 Glu Ser Gly Phe Phe Asp Lys Leu Arg Asn Lys Phe Arg Lys 370 375 380 <210> 41 <211> 1470 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> (101)..(1447) <223> RXS00568 <400> 41 gtttcggacg acgcgagaaa tcgcattaat cgtcggaaac cgggcttgtt tttgtaatat ctgaaacttt ccctttcccg atcatccagg agatttactc gtg aag agt tct gtc 115 WO 01/00804 WO 0100804PCT/IBOO/00922 Val Lys Ser Ser Val 1 gag aag ctg Giu Lys Leu tct gaa ctg Ser Giu Leu caa gtc cag Gin Val Gin atc gac gca Ilie Asp Ala gao atg ct Asp Met Leu aag gca atc Lys Aia Ile gag oto gtt Glu Leu Val ctt cct aag Leu Pro Lys 120 gac gaa gag Asp Giu Giu 135 tcc acc ttg Ser Thr Leu 150 acc aic aac Thr Ile Asn acc act gag Thr Thr Giu ggc ctg gao Gly Leu Asp 200 agc gac Ser Asp aag cca Lys Pro atc cot Ile Pro cgc tic Arg Phe cot aao Pro Asn ggc cag Gly Gin gag tic Glu Phe 105 tic gag Phe Glu gca atc Ala Ilie aag gat Lys Asp atc acc Ile Thr 170 ggt ctg t Gly Leu 185 aag gct c Lys Ala I acc cgt tca aag a Thr Arg Ser Lys I gag Glu gg t Gi y Gi y cgc Arg 75 cct Pro gt c Val ga c Asp gaa Glu cac Hjis 155 gca kia :cc e r :tg ~eu Iatc I le ttc Phe cgt Arg 60 tac Tyr aac Asn gct Aila atc Ile gca Ala 140 aac Asn agc Ser tac Tyr atc Ile gac Asp cgt Arg 45 ggt Gly gca Ala gt a Val gag Glu act Thr 125 gag Giu ca c His att Ile gaa Giu ggc Gly 205 cag Gin 30 aag Lys gcg Al a ca g Gin gag Glu gt t Vai 110 gtt Val1 ctc Le u aag Lys gac Asp atc Ile 190 gct A~la 9
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tc acc gtt ie Thr Val 15 ca tao gcc la Tyr Ala gc aag gca ly Lys Ala it ctg gag al Leu Giu ca aic gaa ia Ile Giu 80 to acc aag al Thr Lys 95 ac gtt ogc sp Val Arg ag gto oca lu Val Pro ag aco ctg Lu Thr Leu 145 :g aag aag au Lys Lys 160 ~t gag aag Ly Giu Lys 15 ja tot gac -y Ser Asp g aag gat rs Lys Asp gag~ Giu got Ala cog Pro cag Gin gct Al a at c Ile oca Pro gct Ala 130 cgt Arg ggt Gi y tt Ile ga t gaa 210 gt IVal cta Leu cgt Arg gitt Val1 gag Giu gaa Glu gag Glu 115 atc Ile goa Al a gag Giu gaa Giu cig Leu 195 acc Thr oca Pro gog Ala cag Gin gto ValI ggC Gly gao Asp 100 to Phe aag Lys ogt Arg tto Phe gag Giu 180 at Ile gta Val ttt Phe cag Gin ct Leu aac Asn atc Ile aac Asn gag Giu got Ala to Phe gic Val 165 gca Aia gao Asp gag Glu 163 211 259 307 355 403 451 499 547 595 643 691 739 to aoc tot gag ctg gca aao ggo gag aaggoaggagtoa Phe Thr Ser Glu Leu Ala Asn Gly GluHiLyGyLyGlAaGn cac aag ggc aag gaa gct caa His Lys Gly Lys Glu Ala Gin wo 01/00804 WO 0100804PCTIBOOIOO922 ate age gtt gag Ilie Ser Val Giu 230 gat gat gag ttc Asp Asp Giu Phe ctt cgt gag tee Leu Arg Giu Ser 265 cag gct get gca Gin Aia Aia Aia 280 gct gac ttc get Aia Asp Phe Aia 295 cag ctg eac eag Gin Leu His Gin 310 aac tee etc ett Asn Ser Leu Leu aag aac gte gaa Lys Asn Vai Giu 345 gac ace etc tct Asp Thr Leu Ser 360 ace gac cac ate Thr Asp His Ile 375 cag tte ate ggt Gin Phe Ilie Giy 390 tee gac gtt cge Ser Asp Val Arg aae gtg aag gac Asn Vai Lys Asp 425 atc Ile gca Ala 250 acc Thr ate Ile ctg Leu etc Leu gag Giu 330 gat Asp gag Giu etg Leu cag Gin cgt Arg 410 tee Ser ac Thi 23~ cac Gir gtg Val] cgc Arc eca Pro etc Leu 315 get Aila qet Aila gtt Vali ttC Phe ctg Leu 395 ggc Gi y gag Giu gca etg Leu tct *Ser *gac Asp cag Gin 300 ca g Gin gag Gi u gag Giu ace Thr 380 cag Gin aag Lys ggt Gly ace Thr get Ala gac Asp gaa Giu 285 tee Ser gag Giu Gi y aag Lys gag Giu 365 gea Aila eag Gin get Al a aac PAsn aag Lys t ct Ser gt t Vai 270 gt t Vali ate Ile et t Leu ace Thr get Aila 350 cc t Pro eag Gin tee Ser ctt Leu gag Gi u 430 eag Gin gag Giu 255 gag Gi u etc Leu gtt Val gca Aia act Thr 335 gt t Vali gag Giu tct Ser gge Giy gea Al a 415 ate Ile ege Arg 240 tte Phe get Ala get Aia gac Asp cac His 320 cgt Arg ege Arg gtt Val tac Tyr ca g Gin 400 cag Gin gae Asp gag Giu gae Asp aag Lys geg Aila gag Giu 305 gac Asp gaa Giu ace Thr tee Ser gge Gi y 385 ate Ile get Ala cct Pro etg Leu ace Thr eag Gin get Aia 290 cag Gin gat Asp gag Giu cag Gin cag Gin 370 atg Met geg Aia ate Ile sag ect.
Pro ate Ile aa g Lys 275 ct t Leu gea Aila get Aia tt C Phe et g Leu 355 cag Gin gac Asp aac Asn tge Cys gaa gag Giu gaa Giu 260 aac Asn gge Giy cac His gca Al a gac Asp 340 ttc Phe gag Giu eca Pro etc Leu ege Arq 420 tac etg Leu 245 gag Giu gag Giu gag Glu tee Ser et g Leu 325 aag Lys etg Leu etc Leu aae Asn tte Phe 405 gt a Vali ttC 835 883 931 979 1027 1075 1123 1171 1219 1267 1315 1363 1411 1457 Lys Giu Tyr Phe 435 ggt gaa gaa gaa gta get gag act gag tet gaa get taaaaacttt Giu Ser Giu Ala Giy Giu Giu 440 Giu Val Ala Giu WO 01/00804 PCTIIBOO/00922 aaagaaataa cgc 1470 <210> 42 <211> 449 <212> PRT <213> CorynebacteriUm glutamicum <400> 42 Val Lys Ser Ser Val Giu Lys Leu Ser 1 Val Ala Ala Giu Gi u Lys Arg Pro Leu 145 Lys Lys Asp Asp Gly 225 Giu Val Ala Leu Pro Arg Gin Val Ala Giu Ile Giu Pro Giu 115 Ala Ilie 130 Arg Ala Gly Giu Ile Giu Asp Leu 195 Glu Thr 210 Lys Glu 5 Pro Phe Ser Ala Gin Gin Gin Leu Ilie Val Asn Asp 70 Gly Ilie Lys Asp Asn Giu 100 Phe Giu Leu Lys Ala Asp Aig Phe Ser 150 Phe Val Thr 165 Giu Ala Thr 180 Ile Asp Giy Val Giu Phe Ala Gin Ile 230 Glu Val1 Asp 55 Met Ala Leu Pro Gi u 135 Thr Ile Thr Leu Thr 215 Se r Leu Gin 40 Ala Leu Ile Val1 Lys 120 Gi u Leu Asn GI u Asp 200 Se r ValI Lys 25 Ile Arg Pro Gly Giu 105 Phe Ala Lys Ile Gly 185 Lys Giu Glu Asp Pro Pro Phe Asn Gin Phe Giu Ile Asp Th r 170 Leu Al a Leu Ile Thr Arg Ser Lys Ile Thr Giu Gly Gly Arg 75 Pro ValI Asp Gi i His 155 Al a Ser Leu Ala Thr 235 Ile Phe Arg Tyr Asn Ala Ile Ala 140 As n Se r Tyr Ile Asn 220 Al a Asp Arg Gly Ala Val Glu Thr 125 Giu His Ile Giu Gly 205 Gly Thr Gin Lys Ala Gin Giu Val1 110 Val1 Leu Lys Asp Ile 190 Ala Giu Lys T yr Lys Leu Ile Thr Val1 ValI Thr Lys 160 Giu Ser Lys Lys Arg 240 Giu Leu Pro Glu Leu Asp Asp Giu Phe Ala Gin Leu Ala Ser Giu Phe WO 01/00804 Asp Thr Ile Glu 260 PCT/IBOO/00922 Glu Leu Arg Giu Ser Thr Val Ser Asp Val Giu Ala 265 270 Lys Ala Gi u 305 Asp Glu Thr Se r Gly 385 Ile Al a Asn Gly His Ala Asp 340 Phe Giu Pro Leu Arg 420 Glu Gin Giu Ala Ser Gin 310 Leu Asn 325 Lys Lys Leu Asp Leu Thr Asn Gin 390 Phe Ser 405 Val Asn Ala Asp 295 Leu Ser Asn Thr Asp 375 Phe Asp Val1 Ala Ala Ile 280 Phe Ala Leu His Gin Leu Leu Leu Glu 330 Val Glu Asp 345 Leu Ser Glu 360 His Ile Leu lie Gly Gin Vai Arg Arg 410 Lys Asp Ser 425 Arg Pro Leu 315 Ala Ala Val1 Phe Leu 395 Gly Glu Giu 285 Ser Glu Gly Lys Giu 365 Ala Gin Al a Asn Pro Lys Glu 435 Ala Tyr Phe Gly Glu Giu Glu Val Ala Glu Thr Giu Ser Giu <210> 43 <211> 826 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> (826) <223> RXN03038 <400> 43 gcgcggaaaa caccaagtaa gccttacagt ccgacagcct catagcggat ggqataagtt ccaaacacgt tcaaatccgt taaagtgcct gtttaaaact atg cat tca aag gaa 115 Met His Ser Lys Giu 1 WO 01/00804 WO 0100804PCT/IBOO/00922 gag Glu gci Ala gca Ala tac Tyr ct Leu acc Thr ccg Pro atg Met ggt Gly acc Thr 150 cca Pro aac Asn atc Ile tta aca Leu agt Ser gct Al a aac Asn ccc Pro gcc Ala cgc Arg gag Glu gat Asp 135 at Ile a cg Thr tgg Trp aac Asn Thr tca Ser caa Gin ccg Pro tac Tyr ica.
Se r tac Tyr cca Pro 120 cgc Arg cct Pro gt c Val1 gt c ValI ct C Leu 200 gig cgt Val Arg atc Ile gac Asp aic Ile tic Phe icc Ser ccc Pro 105 gaa Glu atc Ile cta Leu t ac Tyr acc Thr 185 atc Ile gga.
Gi y tct Ser gat Asp gga Gly 9gc Gi y ct C Le u gitt ValI cgc Arg gtc Val1 gca.
Al a 170 cgc Arg atg Met aaa. gga Lys Gly tic gga Phe Gly gca ttt Ala Phe gac atc Asp Ile 60 agt aaa Ser Lys 75 gtc gig Val Val ggc aaa Gly Lys cit gcg Leu Ala caa aic Gin Ile 140 tgg gt Trp Val 155 ctc gga Leu Gly acc gac Thr Asp ccg atg Pro Met ait tcc cgc gic cic icg gia gcg gti Ile Ser Arg Val Leu Ser Val Ala Val act Thr gac Asp 45 aag Lys ttg Leu acc Thr gac Asp cgc Arg 125 aac As n gt i Val1 Gly ctt Leu ct c Leu 205 gia Val1 30 tac Tyr gat Asp acc Th r icc Se r ga c Asp 110 ct i Leu gcg Al a cca Pro ggt Gly gag Glu 190 gga Gly Cig Leu ggt Gly cgt Arg agc Se r gcg Ala 95 cig Leu gag Glu i ac Tyr ga a Giu ga c Asp 175 gaa Glu tot Ser aca Thr atg Met ccc Pro i gg Trp 80 cic Leu ccc Pro cga Arg i cg Se r gac Asp 160 ggt Gly ta Leu ttt Phe ggc Gly ga t Asp gaa Giu ggc Gly ccg Pro aag Lys iic Phe cca Pro 145 aac Asn gga Gly a cc Thr agt Ser acc Thr c ca Pro gga Gly ica Ser cag Gin gca Al a gic Val1 130 ica Ser acc Th r caa Gin agi Se r itc Phe 210 ggC Gly aac As n tg Leu tca Se r tac Tyr acc Th r 115 99c di y aig Met gig Val1 Gi y ga c Asp 195 tao Tyr ato gca Ile Ala aig aac Met Asn icc aat Ser Asn tai gc Tyr Ala acc gat Thr Asp 100 aic gao Ile Asp gtt gac Val Asp gga cgc Gly Arg cct ggc Pro Gly 165 ggc cag Gly Gin 180 aac aac Asn Asn tct gac Ser Asp 163 211 259 307 355 403 451 499 547 595 643 691 739 tgg gca cgc gaa Trp Ala Arg Glu 215 ago caa icc Ser Gin Ser 220 atg ggi tgt gcg Met Giy Cys Ala caa cag tgq gaa aca Gin Gin Trp Glu Thr 225 WO 01/00804 ttg ctc atg cac gaa ctg cct gag ccg ctt gta gcg gcc Leu Leu Met His Glu Leu Pro Glu Pro Leu Val Ala Ala 230 235 240 <210> 44 <211> 242 <212> PRT <213> Corynebacterium giutamicum PCTIIBOO/00922 826 <400> 44 Met His Ser Lys Glu Glu Leu Thr Val 1 Leu Gly Asp Glu GI y Pro Lys Phe Pro 145 As n GI y Thr Ser Ser Thr Pro Gly Ser Gin Ala Val 130 Ser Thr Gin Ser Phe 210 Val Gly As n Leu Ser Tyr Thr 115 Gi y Met Val1 Gly Asp 195 Tyr Al a Ile Met Ser Tyr Thr 100 Ile Val1 Gly Pro Gly 180 As n Se r 5 Val1 Al a Asn Asn Ala Asp Asp Asp Arg Gly 165 Gin Asn Asp Ala Ala Tyr Leu 70 Thr Pro Met Gly Thr 150 Pro Asn Ile Trp Se r Ala Asn 55 Pro Ala Arg Giu Asp 135 Ile Thr T rp Asn Ala 215 Ser Gin 40 Pro Tyr Ser Tyr Pro 120 Arg Pro Val1 Val1 Leu 200 Arg Ile 25 Asp Ile Phe Ser Pro 105 Giu Ile Le u Tyr Thr 185 Ile Gi u Arg 10 Gly Ser Asp Giy Gly 90 Leu Val Arg Val1 Ala 170 Arg Met Se r Lys Phe Al a Asp Ser 75 Val Gly Leu Gin Trp 155 Leu Thr Pro Gin GI y Giy Phe Ile Lys Vai Lys Ala Ile 140 Val Gly Asp Met Se r 220 Ile Thr Asp Lys Leu Thr Asp Arg 125 Asn Val Gi y Leu Leu 205 Met Ser Val Tyr Asp Thr Ser Asp 110 Leu Al a Pro Gly Giu 190 Giy Gly Arg Val Leu Thr Gly Met Arg Pro Ser Trp Ala Leu Leu Pro Glu Arg Tyr Ser Giu Asp 160 Asp Gly 175 Giu Leu Ser Phe Cys Ala Gin Gin Trp Giu Thr Leu Leu Met His Giu Leu Pro Glu Pro Leu Vai 225 230 235 240 Ala Ala WO 01/00804 WO 0100804PCT/IBOO/00922 <210> <211> 653 <212> DNA <213> Corynebacterium giutamicum <221> CDS <223> RXN03039 <400> gca ctc ccg caa Ala Leu Pro Gin ctg ccc aaa gca Leu Pro Lys Ala gag cga ttc gtc Giu Arg Phe Val tac tcq cca tca Tyr Set Pro Ser gaa gac aac acc Giu Asp Asn Thr gac ggt ggc caa Asp Gly Gly Gin gag ttg acc agt Giu Leu Thr Ser C 100 tct ttt agt ttc t Ser Phe Set Phe T 115 ggt gcg caa cag t Gly Ala Gin Gin T 130 cta gaa gcg gcc a Leu Glu Ala Ala I 145 tac Tyr acc Thr 9gC 31 y atg 4et gtg la 1 ;aa lui :ac yr .gg rp tc le acc gac cca cgc tac ccc ctc ggc aaa Thr Asp Pro Arg Tyr Pro Leu Gly Lys 10 gac gac Asp Asp atc Ile gtt Val gga Gly cct Pro 70 ggC Gly aac Asn gct Ala gaa Giu 9gC Gi y 150 gac Asp ga c Asp cgc Arg 55 ggC Gi y caa Gin aac Asn ga c Asp aca Tb r 135 gca Ala atg Met ggt Gly 40 acc Thr c ca Pro aac Asn atc Ile tgg Trp 120 ttc Phe gac Asp gag Glu gat Asp att Ile a cg Thr tgg Trp aac Asn 105 gca Ala ctc Leu 9 Gly cca gaa Pro Giu cgc atc Arg Ile cct cta Pro Leu gtc tac Vai Tyr gtc acc Val Thr 90 ctc atc Leu Ile ggc gaa Gly Giu atg cac Met His caa cqc Gin Arg 155 gct Al a cgc Arg gt c Val1 gca Ala cgc Arg atg Met agc Set gaa Giu 140 agc Set ctt Leu ca a Gin tgg Trp ctc Leu a cc Thr ccc Pro gaa Giu 125 ctr Xaa at c Ile cgc Arg aac As n gt g Val1 ggC Gly ctt Leu ctc Leu atg Met gag Giu ggc Giy tcc atg tcc ggg gga tcr gtg Set Met Ser Gly Giy Xaa Val 165 ctg aac ttt Leu Asn Phe acg cat gac ccc aac Thr His Asp Pro Asn 175 WO 01/00804 PCTIIBOO/00922 itt iay tcc tck gic ggc tca tit tct gga tgt gcc gaa acc aac tcc 576 Phe Xaa Ser Xaa Val Gly Ser Phe Ser Gly Cys Ala Giu Thr Asn Ser 180 185 190 tgg atg ggr cgc cgn igg cat cgc agc cac tgc cia caa cgq caa tgt 624 Trp Met Xaa Arg Arg Trp His Arg Ser His Cys Leu Gin Arg Gin Cys 195 200 205 cgt gcc tgagcaaatc tttggigaag tag 653 Arg Ala 210 <210> 46 <211> 210 <212> PRT <213> Corynebacierium glutamicum <400> 46 Ala Leu Pro Gin Tyr Thr Asp Pro Arq Tyr Pro Leu Gly Lys Asp Asp 1 Leu Glu Tyr Glu Asp Giu Se r Gi y Leu 145 Ser Phe Pro Arg Ser Asp Gi y Leu Phe Ala 130 Glu Met Xaa 5 Ala Thr Val Gly Ser Met Thr Val Gin Gly Ser Giu 100 Phe Tyr Gin Trp Ala Ile Gly Gly 165 Xaa Val Ile Val Giy Pro 70 Gly Asn Ala Glu Gi y 150 Xaa Gi y Asp Asp Arg Giy Gin Asn Asp Thr 135 Ala Vali Ser Met Gly Thr Pro Asn Ile Trp 120 Phe Asp Leu Phe Giu Pro 25 Asp Arg Ile Pro Thr Vai Trp Val 90 Asn Leu 105 Ala Giy Leu Met Gly Gin Asn Phe 170 Ser Giy 185 Glu Ile Leu Tyr Thr Ile Giu His Arg 155 Ala Cys Leu Gin Trp Le u Thr Pro Giu 125 Xaa Ilie His Glu Ala Ile Val1 Giy Asp Met 110 Ser Xaa Val1 Asp Th r Arg Asn Val1 Gly Leu Leu Mei Giu Gly Pro 175 Asn 180 190 Trp, Met Xaa Arg Arg Trp His Arg Ser His Cys Leu Gin Arg Gin Cys WO 01/00804 195 PCTIIBOO/00922 Arg Ala 210 <210> 47 <211> 432 <212> DNA <213> Cory-nebacterium glutamicum <220> <221> CDS <222> (409) <223> RXN03040 <400> 47 attactctcg ctataaegat cettntgctc aacgctgcga ctctacatct tcgccggttc cggtgtgttc tctgaactag aac Asn ttt Phe gcg Ala ace Thr ttC Phe atc Ilie gtC Val1 ceog att gat gag gat geg t Pro Ile Asp Glu Asp Ala P ate gaa get atg tee aae a Ile Giu Ala Met Ser Asn T gat eaa atg gge atc gac a Asp Gin Met Gly Ile Asp A 45 ace eac gcc tgg gat tac t Thr His Ala Trp Asp Tyr T ttg atg atog eag ggc ttc g Leu Met Met Gin Gly Phe G.
75 aac ect aac ggt gtg ace to Asn Pro Asn Gly Val Thr Si tgatgtgage cttggcacen gtg aaa Lys 15 t ge Cys ate Ile aac Asn etc Leu age Ser 95 agctegaaga acaagacaac atg tea tne ggt. gac Met Ser Xaa Gly Asp 1 ege gte ttg qtt ggg Arg Val Leu Val Gly cat aac etc aag get His Asn Leu Lys Ala tac gat tte cga eca Tyr Asp Phe Arg Pro geg etc cac cgc ttc Ala Leu His Arg Phe ggt ggt ccc ate ccg Gly Gly Pro Ile Pro tet tet ntc aga act Ser Ser Xaa Arg Thr 100 115 163 211 259 307 355 403 432 <210> 48 <211> 103 <212> PRT <213> Corynebacterium glutarnicum WO 01/00804 <400> 48 Met Ser Xaa Gly Asp 1 5 Arg Val Leu Val Gly His Asn Leu Lys Ala Tyr Asp Phe Arg Pro Ala Leu His Arg Phe Gly Gly Pro Ile Pro Ser Ser Xaa Arg Thr 100 PCT/IBOO/00922 Asp Ala Met Al a Met Asn <210> 49 <211> 835 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> (101)..(835) <223> RXN03051 <400> 49 acatccagaa gtagtcgttg agtatcacga gc~ ggaactcccg ctgcctaagc gggacatagt tg aagtcaac gatagtaaag ataatgtcga ::aggggac atg cgt tca gat gtt Met Arg Ser Asp Val 1 gag aaa. gct gac cag cta gaa Glu Lys Ala Asp Gin Leu Glu 15 gca cga ctg atg gca acc acc Ala Arg Leu Met Ala Thr Thr ttc tca gtt tgt ggc cga att Phe Ser Val Cys Gly Arg Ile cag ttg tca tgg ctt ggg cca Gin Leu Ser Trp Leu Gly Pro gac ggt gtt ggc aaa aga agt a tc Ile gtt Val1 ggg Gly ct t Leu ccg gag Glu gcg Al a tgt Cys gac Asp aag gag ggg Glu Gly cga ctt Arg Leu atg tgg Met Trp cgc cag Arg Gin gag ttg aag Lys gg t GI y ggc Gly ggt Gly ccc 115 163 211 259 307 355 WO 01/00804 PCTIIBOO/00922 Pro Lys Ser Asn Glu Leu Thr Asn Pro Asp Gly Val Gly Lys Arg Ser gaa Glu gca Ala tca Se r ccc Pro cca Pro 150 gaa Glu cia Leu att Ile ca g Gin itt ttt Phe Phe gig acc Val Thr ggg cca Gly Pro 120 cit act Leu Thr 135 tig act Leu Thr cit ggc Leu Gly cct agc Pro Ser tcg igg Ser Trp 200 cgg gig Arg Val.
215 ggt gga Gly Gly 90 ttg gac Leu Asp 105 ttg ggg Leu Gly cag cga Gin Arg ggc ggt Gly Gly ggc tcg Gly Ser 170 ggi act Gly Thr 185 cga aai Arg Asn tgg gai Trp Asp gcc aic tat Ala Ile Tyr ggt ttg cga Gly Leu Arg tac cca acc Tyr Pro Thr 125 cag act ttt Gin Thr Phe 140 gct gig tgg Aia Val Trp 155 aat cat gcc Asn His Ala gag tat ttt Giu Tyr Phe gai cgi cag Asp Arg Gin 205 gcg tig ggt Ala Leu Gly 220 cac cca His Pro tgg ggg Trp Gly ggt ccg Gly Pro ggt ggt Gly Gly gat at Asp Ile 160 ggc aic Gly Ile 175 aat aai Asn Asn cgg iii Arg Phe gag acg Giu Thr gac Asp acc Th r atg Met gac Asp 145 aaa Lys ccg Pro tc Phe atg Met ggt Gi y 225 aca Thr tig Leu gati Asp 130 aac Asn cag Gin aic Ile icc Ser tat Tyr 210 cgi Arg ggc Gly aac As n 115 aca Thr tac T yr cgc Arg act Thr aa i As n 195 it g Leu ita Leu cci gaa gca gat gaa aca cci gag git ici ggt cta tic cat Pro Giu Ala Asp Glu Thr Pro Giu Vai Ser Gly Leu Phe His gig gcg Val. Ala 230 235 240 245 <210> <211> 245 <212> PRT <213> Corynebacteriun giutamicum <400> Met Arg Ser Asp Val Ile Giu Leu Pro Giu Gly Val. Ser Lys Glu Lys 1 5 10 Ala Asp Gin Leu Giu Vai Ala Giu Ala Arg Leu Asn Giu Giy Ala Arg 25 Leu Met Ala Thr Thr Gly Cys Giu Val Met Trp Pro Thr Gly Phe Ser WO 01/00804 WO 0100804PCT/IBOO/00922 Val Cys Ser Trp Val Gly Asp Thr Thr Leu Met Asp 130 Asp Asn 145 Lys Gin Pro Ile Phe Ser Met Tyr 210 Gly Arq 225 Leu Phe Arg Ile Leu Asp 55 Gly Pro Pro Lys 70 Arg Ser Giu Phe Ala Tyr Ala Val 100 Trp Giu Ser Giy Asn Tyr Pro Leu 135 Tyr Asn Pro Leu 150 Tyr Giu Giu Leu 165 Asn Giu Leu Pro 180 Gly Thr Ile Ser Ala Thr Gin Arg 215 Gly Phe Pro Giu 230 Val Ala 245 Thr Tyr Arg Gin Val Ser Asn Glu Leu Thr 75 Phe Gly Gly Ala Ile Thr Leu Asp Gly Leu 105 Pro Leu Gly Tyr Pro 120 Thr Gin Arg Gin Thr 140 Thr Gly Gly Ala Val 155 Gly Gly Ser Asn His .170 Ser Gly Thr Glu Tyr 185 Trp Arg Asn Asp Arg 200 Val Trp Asp Ala Leu 220 Ala Asp Glu Thr Pro GI y Asn Tyr Arg Thr 125 Phe Trp Ala Phe Gin 205 Gly Glu Leu Gly Pro Gly Pro Gly Ile 160 Ile Asn Phe Thr Gly 240 <210> 51 <211> 1704 <212> DNA <213> Corynebacterium giutamicum <220> <221> CDS <222> (101)..(168i) <223> RXN03054 <400> 51 ggtggaaata cgcgcacaac aattttattc acagaactta tgattttttc gggttagggt cagtttgttc acatcaacta gtaacgaaag gatcatgtga atq aaa ctg ttt tcc 115 Met Lys Leu Phe Ser WO 01/00804 aag Lys gca Al a ca a Gin gct Ala cct Pro ga t Asp ggC Gly gca Al a tat Tyr gca Ala got Ala ttc Phe ct t Leu cag Gin ca c His ggt Gi y 20 gaa Glu cca Pro PCT/IBOO/00922 ata 163 Ile gac 211 Asp cct 259 Pro gtg ValI cac His Ct c Leu att Ile caa Gln a cg Thr tat Tyr 150 ggc Gly gta Val gag Glu att Ile gat Asp tct Ser ttt Phe 135 att Ile aa ln ga -Asi gct Ali ccg Pro aaa Lys cag Gln 120 t gg Trp cag Gln acg Thr C gg9 p GI -at( IIi ggt Gl) gca Ala 1 05 cca Pro ccg Pro cag Gin tta Leu g gtg y Val *cqa Arg gag Glu gcc Ala cag Gin tca Ser ggt Gly aat c Asn P 170
GI'
ca~ G1 atc Met gc t Al a a cg Thr c~ct Pro ;cc kla 155 :ct ~ro t ggc y G1~ a gc( tgg Trp *gat *Asp cga Arg cat His 140 cag Gin ga t Asp ctac y Tyr caa Gin tca 4Ser gag Glu ggc Gly 125 cag Gin ttt Phe ggtc Gly G aci Th: ga GlI gat Asr gca Aila 110 ct t Leu gtt Val1 9gg U y ~ag ;in t gag caa gaa atc gcc gag atc Giu tct j Ser aag Lys 95 gag Glu gct Ala tgt Cys tgg Trp, ggg t Gly '1 175 act Thr C.
aat g Asn G cct g Pro V Gir Gly 80 gtg Val1 ata I le gcg Ala ggt atg det 160 a t 'yr Giu gca Ala gag Glu got Ala gct Al a gct Ala 145 ttg Leu cgt Ile cct Prc ct g Leu at Ile gog Ala 130 att Ile tt Phe cag Ala aat 4Asn cca Pro gca.
Ala 115 gcg Al a tta Leu ccg Pro Cgg Glu gaa Glu gt a Val1 100 cag Gln t gt Cys gag GI u agt Ser ttt Ile gag Giu act Th r caa Gin cag Gin cgc Arg gaa Giu 165 atg 307 355 403 451 499 547 595 643 Arg Gln Arg Phe Met 180 aat Asn aat Asn a tg Met 9gg Gi y tac Tyr ggt GI y 215 cat ccg His Pro tgg gag Trp Glu 205 ggt gaa Gly Glu 220 aca Thr 190 cgt Arg gtC Val1 gcg Ala tgg Trp aat Asn 225 WO 01/00804 att gat ggt gag Ile Asp Gly Giu 230 PCT/IBOO/00922 835 ttg agt ggg tgq gtg caa act ttc caa ggt ggg cga Leu Ser Giy Trp Vai Gin Thr Phe Gin Gly Gly Arg 235 240 245 gt g ValI ggg Gly ct t Leu a ga Arg gga Gi y 310 gga Giy tat Tyr gct Ala ttt Phe aat Asn 390 caa Gin tat Tyr ctg Leu gg t Gi y ttt Phe 295 gct Aila gct Ala aca Thr aac Asn gct.
A.la 375 tct S er L gt cgc Arg atc Ile t tt Phe 280 t ct Ser cac His gag Giu gaa Giu cta Leu 360 aat Asn cgt Arg ca a Gin agt Se r ttg Leu 265 ccc Pro gtt Val1 cct Pro agt Ser aac Asn 345 tac Tyr ctt.
Leu gta Val( tcg C Ser ccc Pro 250 ga t Asp att Ile ttc Phe at a Ile ggg Gly 330 atg Met ccc Pro gag Glu lag ;iu ~aa ;in gta Val *aaa Lys gcg *Ala ca g Gin tta Leu 315 gaa Giu gct Ala aat Asn gaa Glu gcg Aia 395 tcc Se r ttg gac *Leu Asp tgg ctt.
*Trp Leu gat gag Asp Giu 285 aac gga Asn Giy 300 ggg aat Giy Asn ttc ggt Phe Gly aat cag Asn Gin cct ctt Pro Leu 365 gca ata Ala Ile 380 aat tca Asn Ser gct aac Ala Asn cca aag ggt Gi l gaa Glu 270 gct Al a gt t Val1 ata Ile tac Tyr gta Vai 350 gag Giu gag Gi u ctt Leu at t Ile att ttc Phe 255 Ittg Leu gtg Val gt c Val tac Tyr cct Pro 335 ttc Phe gct Ala tat Tyr aac As n cat His 415 ggg Gly cag gtg Gin Val ggt ggt Gly Gly aca gct.
Thr Ala tac tgg Tyr Trp 305 agt atc Ser Ile 320 atc ggc Ile Giy gaa aaa Giu Lys ttt att.
Phe Ile ttt gag Phe Giu 385 gcc aag Ala Lys 400 gtg aga Val Arg ttt aag Phe Lys cc Ala cct Pro gac Asp 290 cat His tgg Trp, gat Asp ggc Gly gag Gi u 370 aac Asn aaa Lys acg Thr 3ct Al a agt Ser gat Asp 275 ggt Gi y ccg Pro a ga Arg cca Pro gaa Giu 355 ttt Phe gga Gly gat Asp aag Lys agg Arg 435 att, Ile 260 agt.
Se r gtg Val1 caa Gin gaa Glu gaa Giu 340 ctt.
Leu tta Leu t tg Leu t cg Ser agt Ser 420 atg Met aat Asn gac Asp ggt Gly cac His ga a Gi u 325 aaq Lys gca Ala ccc Pro tca Ser att Ile 405 gac Asp ga t Asp 883 931 979 1027 1075 1123 1171 1219 1267 .1315 1363 1411 1459 410 gga gtc Gly Val tgc gac Cys Asp ggg att Gly Ie 425 agg gtt Arg Val Pro Lys Ile 430 ctt cct gga act gtc tca Leu Pro Gly Thr Val Ser gat *gta gtg ggg Asp Val Val Gly tat gga tgg att Tyr Gly Trp Ile.
WO 01/00804 tac tac gac tat tgg gga cga tgg gct Tyr Tyr Asp Tyr Trp Gly Arg Trp Ala 455 460 ttc ttc ggt aat agg aat tct gtt gtg Phe Phe Gly Asn Arg Asn Ser Val Val 470 475 tgc agc gqg gag aag aat aca tta ttt Cys Ser Gly Giu Lys Asn Thr Leu Phe 490 gtg act tat gaa ggt cag ccg tat ttc Val Thr Tyr Glu Gly Gin Pro Tyr Phe 505 510 gct tat ctt ccg tgt acg ata gac cgt Ala Tyr Leu Pro Cys Thr Ile Asp Arg 520 525 gag <210> 52 <211> 527 <212> PRT <213> Corynebacterium giutamicum <400> 52 Met Lys Leo Phe Ser Lys Ala Ala Gly 1 5 Val Ala Gly Gly Ile Ala Pro Val Ala Val Thr Pro Glu Asp Gin Asp Ala Tyr Gly Asn Thr Pro Pro Val Vai Asp Gly 55 Glu Ilie Ala Gu Ilie His Glu Ala Ilie 70 Ala Pro Asn Glu Glu Leu Ile Pro Gly Glu Leu Pro Val Thr Ile Asp Lys Ala 100 105 Ala Ile Ala Gin Gin Gin Ser Gin Pro 115 120 Ala Ala Ala Cys Gin Thr Phe Trp Pro 130 135 Ala Ile Leu Giu Arg Tyr Ile Gin Gin PCT/IBOO/00922 gca gca tat gca caa caa 1507 Ala Ala Tyr Ala Gin Gin 465 acc aat tta gag gcg ggt 1555 Thr Asn Leo Glu Ala Gly 480 485 ggt act tca tat ttt cag 1603 Gly Thr Ser Tyr Phe Gin 500 cag tca gca act aat tac 1651 Gin Ser Ala Thr Asn Tyr 515 taacataagq aatggaatag 1701 1704 Val Ile 10 Gin Gly Val Gin Val Gly Arg Gin Glu Met 90 Ala Ala Gin Thr Ser Pro Gly Ala Al a Gin Gin Gly Ala Trp Asp Arg His 140 Gin Leu Gin His Giu Se r Lys Glu Ala Cys Trp WO 01/00804 PCTABOO/00922 145 150 155 160 Leu Phe Pro Ser Glu Gly Gin Thr Leu Asn Pro Asp Giy Gin Gly Tyr 165 170 175 Arg Gin Arg Phe Met Asn Gly Phe Vai Tyr Trp His Pro Thr Thr Gly 180 185 190 Ala His Ala Val Asn Asn Tyr Ser Ala Gin Val Trp Giu Arg Asn Gly 195 200 205 Trp Glu Ser Gly Trp Met Gly Tyr Pro Thr Gly Gly Glu Vai Pro Val 210 215 220 Asn Gly Ser Asn Pro Ile Asp Gly Glu Leu Ser Gly Trp Val Gin Thr 225 230 235 240 Phe Gin Gly Giy Arq Vai Tyr Arg Ser Pro Val Leu Asp Giy Phe Gin 245 250 255 Val Ala Ser Ile Asn Gly Leu Ile Leu Asp Lys Trp Leu Giu Leu Giy 260 265 270 Giy Pro Asp Ser Asp Leu Gly Phe Pro Ile Ala Asp Giu Ala Val Thr 275 280 285 Ala Asp Giy Val Gly Arg Phe Ser Val Phe Gin Asn Giy Vai Val Tyr 290 295 300 Trp His Pro Gin His Gly Ala His Pro Ile Leu Gly Asn Ile Tyr Ser 305 310 315 320 Ile Trp Arg Glu Giu Gly Ala Giu Ser Gly Giu Phe Gly Tyr Pro Ile 325 330 335 Gly Asp Pro Giu Lys Tyr Thr Giu Asn Met Ala Asn Gin Val Phe Glu 340 345 350 Lys Gly Giu Leu Ala Ala Asn Leu Tyr Pro Asn Pro Leu Giu Ala Phe 355 360 365 Ile Giu Phe Leu Pro Phe Ala Asn Leu Giu Giu Ala Ile Giu Tyr Phe 370 375 380 Glu Asn Gly Leu Ser Asn Ser Arg Vai Giu Ala Asn Ser Leu Asn Aia 385 390 395 400 Lys Lys Asp Ser Ilie Gin Cys Gin Ser Gin Ser Ala Asn Ile His Vai 405 410 415 Arg Thr Lys Ser Asp Gly Val Giy Ile Arg Val Pro Lys Ile Gly Phe 420 425 430 Lys Ala Arg Met Asp Cys Asp Leu Pro Giy Thr Val Ser Asp Vai Val 435 440 445 Gly Tyr Gly Trp Ilie Tyr Tyr Asp Tyr Trp Gly Arg Trp Ala Gin Ala WO 01/00804 450 455 460 Ala Tyr Ala Gin Gin Phe Phe Gly Asn Arg Asn Ser Val Val Gin Thr 465 470 475 480 Asn Leu Glu Ala Gly Cys Ser Gly Glu Lys Asn Thr Leu Phe Trp Gly 485 490 495 Thr Ser Tyr Phe Gin Val Thr Tyr Giu Gly Gin Pro Tyr Phe Gly Gin 500 505 510 Ser Ala Thr Asn Tyr Ala Tyr Leu Pro Cys Thr Ile Asp Arg Ser 515 520 525 PCT/IBOO/00922 <210> 53 <211> 456 <212> DNA <213> Corynebacterium glutamicum <2 <221> CDS <222> (101)..(433) <223> R.XN02949 <400> 53 actctcgaag gttqaacaca gggctgcgat tgtgctggat caaatgtctg cacgaaaaat tgttatcgcc cctggatgag tagtgattta gaggagtgct gtg agc gac gag cag Val Ser Asp Glu Gin a at Asn t cg Ser t ct Se r gt t Val1 t gg Trp ttc ggc Gi y gc t Al a cag Gin t ct Ser act Thr att gt a Val tcc Ser a ag Lys ttt Phe gcg Ala gt t ValI ggc Gi y act Thr aag Lys ctg Leu cgc Arg t tg gga Gly acc Thr tca Ser c ct Pro cag Gin 75 acc acg tct Thr Ser tct acc Ser Thr tcc ggt Ser Gly 45 gag gtt Glu Val atg gtc Met Val gct ttg cgc Arg t Ct Ser 30 tcg Se r gtg ValI acg Th r gt g a cg Thr tat Tyr t Ct Ser gaa Glu acc Thr ggt
I
ggt Gly gag Glu a ag Lys gtc Val ctt Leu gtg aaa Lys gct Ala cct Pro cgt Arg gtc Val1 gat cgc Arg aag Lys ggc Gly aag Lys gt t ValI ttc Phe Leu Ile Leu Thr Ala Leu Val Ser 95 Gly Val Asp Phe Leu Ala 100 ggt ctt gga gtt gag aag att ctg act ccg taggtaggat gtgtaacatc WO 01/00804 PCT/IBOO/00922 Gly Leu Gly Val Giu Lys Ile Leu Thr Pro 105 110 ttt 456 <210> 54 <211> 111 <212> PRT <213> Corynebacteriun giutamicum <400> 54 Val Ser Asp Glu Gin Asn Ser Gly Val Gly Gly Thr Ser Arg Pro Thr 1 5 10 Gly Lys Arg Gin Leu Ser Gly Ala Ser Thr Thr Ser Thr Set Ser Tyr 25 Glu Ala Lys Gin Val Ser Thr Gin Lys Lys Ser Ser Gly Ser Asp Ser 40 Lys Pro Gly Gly Gly Vai.Iie Ser Phe Leu Pro Glu Val Val Gly Giu 55 Val Arg Lys Val Ile Trp Pro Thr Ala Arg Gin Met Val Thr Tyr Thr 70 75 Leu Val Val Leu Gly Phe Leu Ile Val Leu Thr Ala Leu Val Ser Gly 90 Val Asp Phe Leu Ala Gly Leu Giy Val Glu Lys Ile Leu Thr Pro 100 105 110 <210> <211> 1941 <212> DNA <213> Corynebacterium-giutamicum <22 0> <221> CDS <222> (1918) <223> RXN02462 <400> tccatcctca tcgacgaagc ccgcacccca ctgattatct ccgggaccag tagacggcac atcgcagttc tacaacgtct tcgcacagat cgtcccacgc atg acc aag gac gtt 115 Met Thr Lys Asp Val 1 cac tac gaa gtc gac gaa cgt aaa aag acc gtc ggt gtg aaa gaa gaa 163 His Tyr Giu Val Asp Giu Arg Lys Lys Thr Val Gly Val Lys Giu Glu 15 ggc gic gaa tac gtc gaa gac caa ctc ggc atc gac aac ctc tac gca 211 Gly Val Giu Tyr Val Glu Asp Gin Leu Gly Ile Asp Asn Leu Tyr Ala wo 01/00804 WO 0100804PCT/IBOO/00922 ct Pro cag Gin gtt ValI tac Tyr ate Ile tte Phe ga a Giu cca Pro 150 aaa Lys cgc Arg cgc Arg aac Asn cag Gin gag Glu gaa Glu atg Met aae As n aaa Lys ege Arg gea Al a 135 ac Thr ace Thr acc Thr tcc Ser gte Val 215 gea Ala cac His ctg Leu ate Ile gaa Glu aac As n etc Leu 120 gca Ala aae Asn caa Gin ga a Giu ga a Gl u 200 cte Leu ggt Gly tea Ser ttc Phe gte Val gge Giy gag Glu 105 tac T yr gag Giu ega Arg gag Giu aag Lys 185 tac Tyr aat Asn ctt Leu eag Gin ac Th r gac Asp atg Met aae Asn ace Thr etc Leu eca Pro get Ala 170 gge Gly ct c Leu gcg Ala cea Pro etc Leu egc Arc Giy 75 cac His eag Gin aaa Lys aae Asn aae Asn 155 aa g Lys ca a Gin tee Ser aaq Lys ggc Giy 235 gte Val *gac Asp 60 *ttc Phe ag Gin ace Thr etc Leu cag Gin 140 eag Gin ttc Phe e ea Pro eag Gin cac His 220 gee Ala age Ser 45 aaq Lys ace Thr geg Ala ctg Leu gee Aia 125 ate Ilie cge Arg gca Ala gte ValI ct g Leu 205 cac His gt c Vtal tac Tyr gac Asp Gly ate Ile geg Ala 110 gge Gi y tac Tyr gaa Giu gca Ala etc Leu 190 ttg Leu gag Giu ace Thr etg Leu tac Tyr cgt Arg gaa Giu 95 ace Thr atg Met aag Lys gac Asp gte Val 175 gte Val1 ace Thr eaq Gin gtt Val aae Asn ate Ile gte Val1 80 gee Al a gtt Val ace Thr etc Leu ttg Leu 160 gte Val1 ggt GI y aaa Lys gaa Glu gee Ala 240 aae As n gte Val1 ctt Leu aaa Lys ace Thr ggt Gly gae Asp 145 ace Th r ga e Asp ac Thr ega Arg gea Ala 225 ace Thr gaa Glu gee Ala ege Arg gee Ala gag Giu etc Leu ace Thr 130 gte ValI gac Asp gac Asp gte Val ggc Gly 210 ca g Gin aae Asn ate aag Ile Lys aac gge Asn Gly gge ege Gly Arg ego gta Arg Val 100 cag aac Gin Asn 115 gca gag Ala Giu ate geg Ile Ala ttg gtg Leu Val ate gea Ile Ala 180 tee gte Ser Val 195 ate aag Ile Lys ate gtt Ile Val atg geg Met Ala gea Ala ga a Glu cga Arg gag Gilu tac Tyr ace Th r ate Ile tac Tyr 165 ga a Giu gag Giu cac His get Al a ggc Gly 245 259 307 355 403 451 499 547 595 643 691 739 787 835 883 egt gga ace gac ate Arg Gly Thr Asp Ile 250 gtg etc ggc gga aac eca Val Leu Gly Gly Asn Pro 255 ate etc etc gao Ile Leu Leu Asp 260 WO 01/00804 etc aaa etc cgc IlIe tac T yr gaa Giu Gly 310 cgt Arg atg Met atg Met ace Thr eac Asn 390 gaa Giu gea Ala gca Al a ctc Le u Lys ceg Gin gaa Giu 295 cc Thr tct Se r eye Arg atg Met gtc ValI 375 ttc Phe cag Gin gec Asp tec Tyr gec Asp 455 Leu gaa Giu 280 cgt Arg gaa Glu gca Ala gee Asp eec Asn 360 ace Thr gae Glu cgc Arg ate Ile gte Val 440 aaa Lys Arg 265 gee Al a ggc Gi y ego Arg cgt Arg gee Asp 345 agg Arg ac Asn atg Met aag Lys tcc Ser 425 gee Asp etc Leu gae cgt Giu Arg tgg gao Trp Asp gac aa Asp Lys eac ga His Glu 315 ceg ggc Gin. Gly 330 ctg atg Leu Met etc aac Leu Asn tec etc Ser Ile cgt eag Arg Lys 395 gtt ate Val Ile 410 egc tee Arg Tyr ggc gee Gly Ala tgg eec Trp Asn gga Gi y get Al a gtc Val1 300 tee Ser gee Asp gtt Val1 gte Val aeg Lys 380 aec Asn tee Tyr etc Ile ace Thr gee Ale 460 Leu gae Giu 285 cgc Arg ega Arg cea Pro ege Arg cc a Pro 365 ggc Gly gt t Val age Ser cee Gin gee Al a 445 ct c Leu Asp 270 ctt Leu gee Giu ege Arg gga Gi y ttc Phe 350 gee Asp gee Ala ctg Leu gag Glu eec As n 430 eec As n gee Giu Pro ecea Pro gee Al a ate Ile tee Se r 335 gte Vali get Asp cee Gin aeg Lys ega Arg 415 etg Met gge Gly gee Ala *Phe gee *Ale gge Gly gee Asp 320 ace Thr gyC Giy gtg Val get Al a tee Tyr 400 eye Arg etc Ile tee Tyr etc Leu Asp Giu 275 aeg cay Lys Gin 290 etc tee Leu Tyr cay ety Gin Leu tte tat Phe Tyr eec atg Thr Met 355 etc gee Ile Giu 370 gty gag Val Giu gee gte Giu Val etc etc Ile Leu gee ace Giu Thr 435 gee gee Giu Asp 450 gee cea Asp Pro Giu eye Arg gte ValI ego Arg etc Leu 340 gaa Giu tee Se r eec As n etg Met gee Giu 420 gte Vali t gg Trp tog Ser ott gat cot ttc gee gee gee gee age Ser t go Cys ctt Leu gyt Giy 325 tot Ser eec As n aa Lys ce g Gin eec As n 405 tee Se r aye Ser gee Asp etc Ile PCT/IB00100922 931 979 1027 1075 1123 1171 1219 1267 1315 1363 1411 1459 1507 eec tg Asn Trp 470 ace gee etc gte gea ggc age gee tao Thr Asp Leu Val Glu Gly Ser Giu Tyr 475 480 ggc aae eca gyg gag 1555 Gly Lys Pro Giy Giu 485 WO 01/00804 ct g Leu ga a Gi u cag Gin aaa Lys ggc Gly 550 gaa Glu acc Th r tcc gcc gaa gat cta Ser Ala Glu Asp Leu 490 tac gca aaa ctc gaa Tyr Ala Lys Leu Glu 505 atc cgc aac atc gaa Ile Arg Asn Ile Glu 520 tgg cgc gaa cac ctc Trp Arg Glu His Leu 535 ctg cqc gca atg qca Leu Arg Ala Met Ala 555 ggc ggc gac atg ttc Gly Gly Asp Met Phe 570 gtc cgc cag ctc ttc Val Arg Gin Leu Phe 585 cgc acc gca ctc gtc aac gac gcc cac gcc Arg Thr Ala Leu Val Asn Asp Ala his Ala gaa gcc Glu Ala cga atg Arg Met 525 tac gaa Tyr Glu 540 cag cgc Gin Arg aac ggc Asn Gi1y ctc tcc Leu Ser 495 t cc Ser ctc Leu gac Asp cc a Pro aaa Lys 575 agc Ser ggc Gly gt c Vai 530 aaa Lys gaa Giu atc Ile t ca Se r PCTIBOOIOO922 1603 1651 1699 1747 1795 1843 1891 cgg aag tcg ctg act aac tca gaa ccc Arg Lys Ser Leu Thr Asn Ser Giu Pro 600 605 atg <210> 56 <211> 606 (212> PRT <213> Corynebacteriun giutamicum <400> 56 Met Thr Lys Asp Val His Tyr Glu Val 1 Gly Val Lys Giu Glu Giy Val Giu Tyr 25 Asp Asn Leu Tyr Ala Pro Giu His Ser Asn Ala Ile Lys Ala Gin Giu Leu Phe Val Arg Asn Gly Giu Val Met Ile Val Leu Ala Gly Arg Arg Tyr Asn Giu Gly tgaaattcag catccgccac 1938 1941 Lys Leu Tyr Asp Gly Ile WO 01/00804 WO 0100804PCTIIBOO/00922 Lys Thr Gly Asp 145 Tb r Asp Thr Arg Al a 225 Thr Glu Giu Met Gi y 305 As n Arg Pro Pro Giu Leu Thr 130 Val1 Asp Asp Val Gly 210 Gin Asn Ile Asp Lys 290 Leu Gin Phe Thr Ile Arg Gin 115 Al a Ilie Leu Ile Ser 195 Ile Ile Met Leu Giu 275 Gin Tyr Leu Tyr Met 355 Giu Val 100 As n Gi u Ala Val1 Ala 180 Val1 Lys Val1 Aila Leu 260 Glu Arg Val Arg Leu 340 Gi u Ser *Glu Tyr Thr Ile Tyr 165 Giu Giu His Aila Giy 245 Asp Ser Cys Leu Gly 325 Ser Asn Lys Ile Phe Glu Pro 150 Lys Arg Arg Asn Gin 230 Arg Ile Tyr Giu Gi y 310 Arg Met Met Thr Lys Arg Ala 135 Tb r Thr Thr Ser Val 215 Al a Gi y Lys Gin Giu 295 Thr Ser Arg Met Val Asn Leu 120 Ala Asn Gin Glu Gi u 200 Leu Gly Thr Leu Glu 280 Arg Glu Al a A'sp Asn 360 rhr Giu 105 Tyr Giu Arg Gi u Lys 185 Tyr As n Leu Asp Arg 265 Al a Gly Arg Arg Asp 345 Arg Asn As n Thr Leu Pro Al a 170 Gly Leu Al a Pro Ile 250 Giu Trp Asp His Gin 330 Leu Leu Ser *Gin Lys Asn Asn 155 Lys Gin Se r Lys Gly 235 Val Arg Asp Lys Giu 315 Gly Met Asn Ile Thr Leu Gin 140 Gin Phe Pro Gin His 220 Al a Leu Gly Ala Val1 300 Ser Asp Val1 Val Lys Leu Ala 110 Ala Gly 125 Ile Tyr Arg Giu Ala Ala Val Leu 190 Leu Leu 205 His Glu Val Thr Gly Gly Leu Asp 270 Giu Leu 285 Arg Glu Arg Arg Pro Gly Arg Phe 350 Pro Asp 365 Giy Ala Thr Met Lys Asp Val1 175 Val1 Thr Gin Val1 Asn 255 Pro Pro Ala Ile Ser 335 Val Asp Gin 370 380 Gin Val Glu Asn Gin Asn Phe Glu Met Arg Lys Asn Val Leu Lys Tyr WO 01/00804 WO 0100804PCT/IBOO/00922 385 390 395 400 Asp Glu Val Met Asn Glu Gin Arg Lys Val Ile Tyr Ser Glu Arg Arg 405 410 415 Giu Ile Leu Giu Ser Ala Asp Ile Ser Arg Tyr Ile Gin Asn Met Ile 420 425 430 Giu Giu Thr Val Ser Ala Tyr Val Asp Gly Ala Thr Ala Asn Gly Tyr 435 440 445 Val Giu Asp Trp Asp Leu Asp Lys Leu Trp Asn Ala Leu Giu Ala Leu 450 455 460 Tyr Asp Pro Ser Ile Asn Trp Thr Asp Leu Val Glu Gly Ser Giu Tyr 465 470 475 480 Gly Lys Pro Gly Giu Leu Ser Ala Giu Asp Leu Arg Thr Ala Leu Val 485 490 495 Asn Asp Ala His Ala Glu Tyr Ala Lys Leu Giu Giu Ala Val Ser Ala 500 505 510 Ilie Gly Gly Giu Ala Gin Ile Arg Asn Ile Giu Arq Met Vai Leu Met 515 520 525 Pro Val Ilie Asp Thr Lys Trp Arg Giu His Leu Tyr Giu Met Asp Tyr 530 535 540 Leu Lys Giu Gly Ilie Gly Leu Arg Ala Met Ala Gin Arg Asp Pro Leu 545 550 555 560 Val Giu Tyr Gin Lys Glu Gly Gly Asp Met Phe Asn Gly Met Lys Asp 565 570 575 Gly Ilie Lys Giu Giu Thr Val Arg Gin Leu Phe Leu Ser Ala Ser Scr 580 585 590 Ser Ser Ser Lys Thr Arg Lys Ser Leu Thr Asn Ser Giu Pro 595 600 605 <210> 57 <211> 1965 <212> DNA <213> Corynebacterium giutarnicum <220> <221> CDS <222> (1942) <223> RXN0i559 <400> 57 gtctggttga ttggaattga aggagacttt cttggctcgg caaaaaaaga gtgccgctag cgcctgggaa cgatggccaa aacgcgcaat agcgttgttt gtg ctc atc gtc gtt 115 Vai Leu Ile Val Vai WO 01/00804 WO 0100804PCT/IBOO/00922 ggt Gly aaa Lys cag Gin ctg Leu got Ala Cag Gin ggt Gly gag Glu gca Al a gog Ala 150 gcg Al a cgc Arg 000 Pro gtt ValI t tg Leu 9gg Gly gaa G iu gac Asp gog Ala cag Gin at g Met aat Asn 135 gt g Val1 ace Thr cag Gin act Thr go~g Ala att Ile ga t Asp e t.
Arg aa c Asn too Ser gga Gly 105 aac Asn toe Ser qgo Gly aig Met ato Ile 185 cag Gin ttg Leu gat Asp cca Pro gt g Val1 acg Th r ct a Leu atg Met agg Arg ttg Leu ga a Gi u ga t Asp 170 acg Thr ate Ile gtg cig Val Leu ctg caa Leu Gin act cag Thr Gin aac ggc Asn Gly 60 ctg gtg Leu Val 75 gga cag Gly Gin ccc gat Pro Asp tgg gtt Trp Val gag gaa Giu Giu 140 gaa gca Glu Ala 155 gag cca Giu Pro gac atg Asp Met got gca Ala Ala ttg aca Leu Thr ggc gga Gly Gly ~30 gao cag Asp Gin atg ggc Met Gly ate act Ile Thr acc toe Thr Ser atg ace Met Thr 110 gaa tao Glu Tyr 125 atg aao Met Asn act gag Thr Giu goc aao Ala Asn otg cgo Leu Arg 190 agt tot Ser Ser 205 ggc gat Giy Asp 15 aoc oga Thr Arg otg aat Leu Asn gtt toa Val Ser gtt 000 Vai Pro oag ctg Gin Leu 95 acg ttg Thr Leu ggo gto Giy Val aec got Thr Ala oca gaa Pro Giu 160 too att Ser Ilie 175 aco gao Thr Asp ttq atg Leu Met egt tot goO aoa Arg Ser Ala Thr gtg aoo etc gtg Val Thr Leu Val oag goa ogo aco Gin Aia Arg Thr ggt goa ago gtg Gly Ala Ser Vai gqg gaa aat aoo Gly Giu Asn Thr etg tte ogt 000 Leu Phe Arg Pro 100 atg oca gag otg Met Pro Giu Leu 115 ato ace gaa gag Ile Thr Giu Giu 130 gtt gca tog aoo Val Aia Ser Thr 145 ccc gto aoc gtg Pro Val Thr Val gag goa aoa. oag Glu Ala Thr Gin 180 ogc eag too aco Arg Gin Ser Thr 195 oag tgo ace act Gin Cys Thr Thr 210 cgo ctg oca ttg gag atg gat ect ttg geo ggc aoo Giu Met Asp Pro Leu Aia Gly Thr gat gat eca Asp Asp Pro Arg 225 Leu Pro Leu gca Ala 230 ttg Leu aa t Asn tcC Ser gaa Glu cag Gin 310 cag Gin act Th r ttg Leu acc Th r atc Ile 390 tac Tyr ggC Gly WO 01/00804 tgt gat cca Cys Asp Pro ctc aac ggc Leu Asn Giy gag atc gat Giu Ile Asp 265 ggc cag atg Giy Gin Met 280 ggc tct gca Giy Ser Ala 295 aic gcc atc Ile Aia Ilie tca gca acc Ser Ala Thr caa act gaa Gin Thr Giu 345 ccc ctg agc Pro Leu Ser 360 acc gtt ccg Thr Val Pro 375 gca ggc atc C Ala Gly Ilie tac cgc gtc t Tyr Arg Vai F 4 gtg ttg gtc: t Vai Leu Val TI 425 gct Ala gaa Glu 250 acc Thr ga a Ci u act Thr acc Thr cct Pro 330 gcC Ala tC Phe :ca Pro t c al1 ;tc ~he 10 ac yr gta Val1 235 acc Thr aac As n atc Ile t gg Trp ctg Leu 315 gtg Val1 caa Gin gca Ala t ca Ser ggc Gly 395 gga Gly ggc Gi y gg t Giy ga t Asp Cgt Arg agc Ser t cc Se r 300 gac Asp ggt Gly gat Asp ggt Gly cta Leu 380 atc Ile ttc Phe ctt Leu ggc Gly gag Giu ccc Pro ttt Phe 285 tct Ser t ct Ser t ct Ser ctg Leu ga a Glu 365 ggc Gly gcg Ala gt t Val1 ctg Le u gtg Val gaa Glu atc Ile 270 gcc Ala ctg Leu cag Gin gca Ala gcg Ala 350 aac Asn gca Ala ctg Leu tcc Ser gta Val1 430 tat T yr aat Asn 255 acc Thr ttc Phe acc Th r gtg Val1 aca Thr 335 aac Asn 9gc Gly gca Al a gt C Val1 ct g Leu 415 ctg Leu g ta Val 240 ggt Giy ggt Gly aaa Lys agc Ser att Ile 320 t cc Ser aac Asn gag Glu tcC Ser gcc Ala 400 ttc Phe ctg Leu ct t Leu gcg Al a gga GI y tcc Se r cag Gin 305 tct Ser atc Ile ctg Leu cgc Arg ttg Leu 385 at c Ile acc: Thr gga Gly gat cct Asp Pro cgc cta Arg Leu ttc aac Phe Asn 275 ggc gat Gly Asp 290 tac ctg Tyr Leu gca ccc Ala Pro acc ggt Thr Gly cgc tac Arg Tyr 355 ggc gga Gly Gly 370 aag gcc Lys Ala ttc gtg Phe Val ceg ttt Leu Phe cgc tgq Arg Trp 435 PCTIBOO/00922 835 883 931 979 1027 1075 1123 1171 1219 1267 1315 1363 1411 tat tcc cta gac: ctt gct Tyr Ser Leu Asp Leu Ala 4 40 ggt atc gcc ggt Gly Ile Ala Gly 445 ttg atc atc Leu Ile Ile 450 ggt atc ggt Gly Ile Gly 1459 WO 01/00804 aec ace gcc gac Thr Thr Ala Asp 455 PCT/IBOO/00922 cgc atc aag gat gag 1507 Arg Ile Lys Asp Glu tee ttc gtg gtg ttc tat gag Ser Phe Val Val Phe Tyr Glu 460 ate cgt Ile Arg 470 agc gee Ser Ala gct atc Ala Ile ttc acc Phe Thr ate acg Ile Thr 535 aag tca Lys Ser 550 cgc ege Arg Arg cat gcc His Ala act gac Thr Asp gaa Glu aag Lys gtg Val1 ctg Leu 520 gca Ala tcg Ser gcc Ala aag Lys aat gga Gly ege Arg att Ile 505 ggt Gly cca Pro gte Val sac Asn aat Asn 585 tct aga Arg ace Th r 490 tac T yr Ct 9 Leu ct g Leu aac Asn ggt Gly 570 gcg Al a ga a tee ttt Ser Phe 475 ate gte Ile Val ttg etc Leu Leu ace ace Thr Thr gtt ate Val Ile 540 ggc atg Gly Met 555 gaa ttg Glu Leu ges get Ala Ala gca cct Ala Pro aga Arg aca Th r geg Al a gta Val 525 et g Leu gga Gly ga t Asp ga t Asp tct Ser ggC Gly gtC ValI 510 tte Phe ges Ala ega Arg gag Glu aag Lys 590 gta Val1 480 atg Met ga Glu etc Leu eqe Arg at g Met 560 gag Glu t cc Ser egt Arg act Thr sag Lys gte Val1 530 ee a Pro etc Leu etg Leu gac Asp tgg Trp etc Leu 500 ttt Phe tte Phe ttt Phe gaa.
Glu aag Lys 580 tct Se r gaa Glu 485 ggC Gly gee Ala ct g Leu gee Al a gas Glu 565 ate Ile tee Ser 1555 1603 1651 1699 1747 1795 1843 1891 1939 1965 Asn Ser Giu gge aee: Gly Thr 605 gat Asp aeg aac cas Thr Asn Gin 610 gag gag gag Glu Glu Glu 600 sag Lys tagccatgac tgattcecag set <210> 58 <211> 614 <212> PRT <213> Corynebseterium glutamicum <400> 58 Val Leu Ile Val Val Gly Val. Tyr Ala Leu Va.' Leu Leu Thr Gly Asp 1 5 10 Arg Ser Ala Thr Pro Lys Leu Gly Ile Asp Leu Gin Gly Gly Thr Arg 25 WO 01/00804 PCT/IBOO/00922 Val Thr Leu Val Pro Gin Gly Gin Asp Pro Thr Gin Asp Gln Leu Asn -is 40 Gin Ala Gly Ala Gly Glu Leu Phe Met Pro Ile Thr 130 Val Ala 145 Pro Val Glu Ala Arg Gin Gin Cys 210 Arg Leu 225 Leu Asp Ala Arg Gly Phe Ser Gly 290 Gin Tyr 305 Arg Ser Asn Arg Glu 115 Gi u Se r Thr Thr Ser 195 Thr Pro Pro Leu As n 275 Asp Leu Ile Leu Val Ala 70 Ala Gin Val Gly Glu Glu Gin Ala Thr Ala 150 Ser Ala 165 Arg Arg Asp Pro Asp Glu Val1 Ala 230 Pro Leu 245 Gly Asn Gin Ser Giu Giu Gin Gin 310 Glu Asp Ala Gin Met Asn 135 Val1 Thr Gin Th r Met 215 Cys Leu Giu Gly Gi y 295 Ile Asn Arg Gly Asn Gin Ser Ala Gly 105 Ala Asn 120 Ala Ser Glu Gly Pro Met Glu Ile 185 Val Gin 200 Asp Pro Asp Pro Asn Gly Ile Asp 265 Gin Met 280 Ser Ala Ala Ile Asn Leu Gly Pro Trp Glu Glu 155 Glu Asp Ala Al a Val1 235 Thr Asn Ile Trp Leu 315 Ser Ala Pro Val Ilie Gin Ser Ala Thr Pro Val Gly Ser Ala Thr Ser WO 01/00804 WO 0100804PCT/IBOO/00922 Ile Thr Gly Phe Thr Gin Thr Glu Ala Gin Asp Leu Ala Asn Asfl 345 350 Leu Arg Arg Gly 370 Leu Lys 385 Ilie Phe Thr Leu Gly Arg Ilie Ile 450 Arg Ile I 465 Pro Arg IZ Val Thr 1 Vai Lys G Vai Val TI 530 Asn Pro P 545 Lys Leu V Tyr Leu L Thr Asp A Asn Gin G 610 <210> 59 <211> 819 Tyr 355 Gly Al a Val1 Phe rrp 235 ;iy .ys la ~eu ;iy hr he alI ys sn 95 lu Gly Thr Gi y Phe Aila 420 Ile Ile Asp Trp Leu 500 Phe Phe Phe Glu Lys 580 Ser Giu Al a Thr Le u Ala 405 Aia Gly Gly Glu Gi u 485 Giy Aia Leu Ala Glu 565 Ile Ser Glu Leu Thr Ile 390 Tyr Gly Tyr Th r Ile 470 Ser Ala Phe Ile Lys 550 Arg His Pro Thr 375 Ala Tyr ValI Se r Thr 455 Arg Ala Ile Thr Th r 535 Ser Arg kla Leu Ser 360 Val Pro Gly Ile Arg Val Leu Val 425 Leu Asp 440 Ala Asp Glu Gly Lys Arg Va1 Ile 505 Leu Giy 520 Ala Pro Ser Vai Ala Asn Lys Asn 585 Phe Pro Val1 Phe 410 Tyr Le u Se r Arg Thr 490 Tyr Leu Leu As n Gi y 570 Ala Ala Se r Gi y 395 Giy Gi y Ala Phe Ser 475 Ile Leu Thr Val1 Giy 555 Giu Ala Giy Leu 380 Ile Phe Leu Gly Val 460 Phe Vali Leu Thr Ile 540 Met Leu Ala Giu 365 Giy Ala Val1 Leu Ile 445 Vali Arg Thr Ala Vali 525 Leu Giy Asp Asp Gly 605 As n Aila Leu Se r Val1 430 Ala Phe Ser Gly Val 510 Phe Ala Arg Giu Lys 590 Gi y Ala Val1 Leu 415 Leu Gly Tyr Ala As n 495 cay Asp Se r Val1 Pro 575 Al a Giu Ser Ala 400 Phe Leu Leu Giu Val1 480 Met Gi u Leu Arg Met 560 Glu Ser Thr Asp Lys Ser Giu Ala Pro Thr Asp Thr WO 01/00804 <212> DNA <213> Corynebacteriun glutamicum <220> <221> CDS <222> (796) <223> RXN00046 <400> 59 tggtgcccaa gcagccgtca tcgcagcagc aaaatatgcc PCTIBOOIOO922 cgcgataacg ccttttaaqc acctaaaacg ctgttctcaa cacaggagtt tccttaaata atg gac tta aat act Met Asp Leu Asn Thr caa Gin gt g Val1 cat His ggc Gi y gac Asp atc Ile act Thr acc Thr atg Met ggc GI y 150 cgc Arg caa Gin gtg Val1 ggt Gly gtt Val1 acc Thr gt a Val ttt Phe gcg Al a 135 gcg Ala aag ctc Lys Leu ccc gac Pro Asp gca gcc Ala Aia ggc ggt Giy Giy gtt ttc Vai Phe acc agg Thr Arg tgc gcg Cys Aia 105 gag ctg Glu Leu tgc gca Cys Ala ttt gtg Phe Val tac Tyr Gi y tgt Cys t tg Leu gga Gly 75 gat Asp ga t Asp gt c Val1 act Thr t cc Ser 155 cag Gin gcc Al a ga t Asp ga t Asp acc Thr gt t Val act Thr gt t Val 125 gaa Glu acg Th r ctt caa Leu Gin atg cga Met Arg ggc qgt Gly Gly atc cgt Ile Arg aaa gaa Lys Giu cga gca Arg Ala ttc cga Phe Arg 110 gcc cac Ala His gaa gtt Glu Val ctt gct Leu Ala 99c Gly gat Asp gct Ala t ca Ser ggC Gly gtg Val ct Pro gat Asp ctc Leu gga Gly 160 ct c Leu cat His gcc Al a t cc Se r gaa Glu qaa Giu cct Pro gga Gly 130 gcg Ala acc Th r gag aaa aca Glu Lys Thr ggt cca gat ttc gat tgc ctc cgc gaa gca. cgt Giy Pro Asp Phe Asp Cys Leu Arg Glu Ala Arg WO 01/00804 PCT/IBOO/00922 170 175 180 tta gtt ccc gat gcg ttc ctc att ggc gaa ggt cgc ttc tcc aac cct Leu Val Pro Asp Ala Phe Leu Ile Gly Glu Gly Arg Phe Ser Asn Pro 185 190 195 gcg gat gtg gcg cac ggt cgt ctc att ggt gcc aac gcg atc atc gtg Ala Asp Val Ala His Gly Arg Leu Ile Gly Ala Asn Ala Ile Ilie Val 200 205 2-10 ggc acc gca atc act gac cct ggt ttc atc act gga cag ttc gcg tca Gly Thr Ala Ilie Thr Asp Pro Gly Phe Ile Thr Gly Gin Phe Ala Ser 215 220 225 ctg ttg cac tagcacttag tccagcgctg cac Leu Leu His 230 <210> <211> 232 <212> PRT <213> Corynebacterium glutamicum <400> Met Asp Leu Asn Thr Gin Arg Ser Lys Leu Tyr Ala Gin Leu 1 Gin Thr Pro Ile Ser Ala Arg Se r Se r 145 Ser Th r Cys Val1 T yr Ala Ser Ilie Al a ValI His Gly Asp 70 Ile Thr Thr Met Gly 150 Gin Val Gly Val Thr Val1 Phe Al a 135 Ala Pro Ala Gly Val Thr Cys 105 GI u Cys Phe Gly Cys Leu Gly 75 Asp Asp Val Thr Ser 155 Ala Asp Asp Thr Val Thr Val 125 Gb u Thr Met Gly Ile Lys Arg Phe 110 Ala Glu Leu Gly Asp Al a Ser Gly Val1 Pro Asp Leu Gly 160 Tyr Thr Glu His Arg Glu Lys Thr Val 165 Pro Asp Phe Asp Cys Leu 175 WO 01/00804 Arg Glu Ala Arg Glu Leu Val Pro Asp Ala Phe Leu Ile Gly Glu Gly 180 185 190 Arg Phe Ser Asn Pro Ala Asp Val Ala His Gly Arg Leu Ile Gly Ala 195 200 205 Asn Ala Ile Ilie Val Gly Thr Ala Ile Thr Asp Pro Gly Phe Ile Thr 210 215 220 Gly Gin Phe Ala Ser Leu Leu His 225 230 <210> 61 <211> 1219 <212> DNA <213> Corynebacterium glutamicun <220> <221> CDS <222> (1196) <223> RXN01863 <400> 61 ggtatcatac cgatatgaac caaatagaaa gaaggaagtt taagacgatg aat agc PCT/IBOO/00922 56 104 152 200 248 296 344 392 gtc Val tat Tyr ttt Phe ggt Giy at t Ile aca Thr aaa Lys 100 caa Gin aaa Lys aa t As n caa Gin ctt Leu c ca Pro aag Lys cct Pro ga a Giu 25 ct t Leu act Thr gat Asp a tq Met tat Tyr 105 gt t Val1 cat His t gt Cys gt c Val gaa Giu ttt Phe gca Al a agc Se r qgc Gly aat Asn gac Asp att Ile tct Se r cat His att tac Ile Tyr caa tta Gin Leu atg cgt Met Arg 45 ccc gag Pro Giu cca aat Pro Asn aaa aag Lys Lys cat cga His Arg aat As n act Thr 30 tqt Cys cct Pro ctg Leu tct Se r gg t Gly 110 Met Asn Ser 1 gat cca tgg gaa tca Asp Pro Trp Giu Ser tta agt aac atc gaa Leu Ser Asn Ile Glu agc cac tgt gca gtt Ser His Cys Ala Val tta gat atg gac tta Leu Asp Met Asp Leu cga acg atg tca att Arg Thr Met Ser Ile att aga aat gtt gtt Ile Arg Asn Val Val ata tat aca caa atg Ile Tyr Thr Gin Met 115 WO 01/00804 WO 0100804PCTIIBOO/00922 aat tca aac cta aca ttg cct caa gat cgt tat tta gat att Asn Ser Asn Leu Thr Leu Pro Gin Asp Arg Tyr Leu Asp Ile tat atc Tyr Ile ttc gca Phe Ala gct aag Ala Lys 165 tca gaa Ser Glu 180 acq cta Thr Leu aaa tgt Lys Cys agt caa Ser Gin gat ata Asp Ile 245 ttg cct Leu Pro 260 tca cgt Ser Arg ggc cgt Gly Arg act gat Thr Asp aaa tta Lys Leu gat Asp aa t As n 150 tta Leu caa Gin cca Pro agc Ser tta Leu 230 ttg Leu gtg Val tta Leu agt Se r ttc Phe 310 aca Thr gt t Val 135 gt t Val aaa Lys gga Gly cat His aga Arg 215 aat As n ga t Asp ttt Phe aga Arg cgt Arg 295 gga Gly gat Asp 120 atg cat atc Met His Ile ggc ttt ggc Gly Phe Gly tta tat gaa Leu Tyr Giu 170 atg ttt gta Met Phe Val 185 tta cga aaa Leu Arg Lys 200 cac gag att His Giu Ile gtg tia act Val Leu Thr ttc aga gat Phe Arg Asp 250 cca tgc tta Pro Cys Leu 265 aat gct aac Asn Ala Asn 280 tta aat gtc Leu Asn Val gat gaa aca Asp Glu Thr gta ttt gat Val Phe Asp 330 tca Ser gca Ala 155 caa Gin t ct Ser a ta Ile cac His cta Leu 235 gaa Glu aag Lys aat As n aat Asn ggt Giy 315 aaa Lys cat His 140 atg Met atg Met gc9 Al a cat His cct Pro 220 gcg Al a ga t Asp gat Asp gta Val gt a Val 300 aca Thr t gg Trp 125 aac Asn aag Lys att Ile gaa Giu caa Gin 205 atg Met gaa Glu att Ile gat Asp acg Thr 285 ttt Phe att Ile tta Leu tgg Trp aag Lys tcg Ser a ca Thr 190 gaa Glu tat Tyr atg Met tgg Trp ga a Gi u 270 act Thr aca Thr tcg Ser t cc Ser gga Gly caa Gin aat Asn 175 atg Met gt c Val c ca Pro aaa Lys at g Met 255 ga t Asp aga Arg ggt Gly aat Asn t ct Ser aca Thr cca Pro 160 gca Ala ctc Leu gtt Val gct Al a aag Lys 240 tta Leu caa Gin aat Asn aat Asn ata Ile 320 gat Asp act Thr 145 ccg Pro cgt Arg aat Asn cat His gac Asp 225 aca Thr ttt Phe aag Lys gac Asp gta Val 305 caa Gin ct t Leu gct gaa Ala Glu 130 gat gaa Asp Giu tta aaa Leu Lys aca tta Thr Leu caa agt Gin Ser 195 gat atg Asp Met 210 ttt gca Phe Ala att cat Ile His ggt act Giy Thr tta cta Leu Leu 275 ccg gat Pro Asp 290 atc gta Ile Val aaa gat Lys Asp gct aaa Ala Lvs 440 488 536 584 632 680 728 776 824 872 920 968 1016 1064 1112 325 335 tgt tta gga cca aat gtt tca tta aat tgt cat tgt tcc gag ttt agt WO 01/00804 Ser Leu Asn Cys His Cys Ser Giu Phe Ser Cys Leu Gly Pro Asn Val 340 345 350 355 ctt gtt aaa aat atg tac tat ccg aat atg gat ttt aaa gat aat gag Leu Vai Lys Asfl Met Tyr Tyr Pro Asri Met Asp Phe Lys Asp Asn Giu 360 365 370 cgt cat atg cac aaa caa cca caa att ata caa ttt taaaaactct Arg His Met His Lys Gin Pro Gin Ile Ilie Gin Phe 375 380 taattatgcg gag <210> 62 <211> 383 <212> PRT <213> Corynebacterium giutamicui PCT/IBOO/00922 ii160 1206 1219 <400> 62 Met Asn Ser Val Lys Leu Lys Gin Pro 1 Trp As n Cys Met Met Asn Tb r Ile Thr 145 Pro Arg Glu Ser Ile Glu Ala Val Asp Leu Ser Ile Val Vai Gin Met 115 Ala Glu 130 Asp Giu Leu Lys Thr Leu Tyr Phe Gly Ile Thr Lys 100 Asn Tyr Phe Aia Se r 5 Asn Thr Tyr Tyr Gly Pro Ser Ile Ala Lys 165 Glu Asp Thr Thr Arg 70 Giy Leu Asn Asp As n 150 Leu Gin Val Thr Leu 55 Arg Glu Leu Leu Val1 135 ValI Lys Gly Lys Asn 40 Gin Leu Pro Lys Thr 120 Met Giy Leu Met Giu Leu Thr Asp Met Tyr 105 Leu His Phe Tyr Phe Ser Gly Asn Asp Ile 75 Ser His Gin Ser Al a 155 Gin Se r Ile Gin Met Pro Pro Lys His Asp His 140 Met Met Ala Tyr Leu Arg Glu Asn Lys Arg Arg 125 Asn Lys Ile Giu Asp Pro Leu Ser Ser His Leu Asp Arg Thr Ile Ar g Ile Tyr Leu Asp Giy Thr Gin Pro 160 Asn Ala 175 Met Leu 180 185 190 Asn Gin Ser Thr Leu Pro His Leu Arg Lys Ile His Gin Giu Val Val WO 01/00804 WO 0100804PCT/IBOO/00922 His Asp 225 Thr Phe Lys Asp ValI 305 Gin Leu Pro Asp 210 Phe Ile Gi y Leu Pro 290 Ile Lys Ala As n Arq 215 Asn Asp Phe Arg Arg 295 Gi y Asp Cys Asn His Val Phe Pro As n 280 Leu Asp Val1 His Met 360 Ile Thr Asp 250 Leu Asn Val Thr Asp 330 Ser Tyr Pro 220 Aia Asp Asp Val Vai 300 Thr Trp Phe Asn Tyr Met Trp Giu 270 Th r Thr Ser S er Cys 350 Asp 355 Asp Asn Giu Arg His Met His Lys Gin Pro Gin Ile Ile Gin Phe 370 375 380 <210> 63 <211> 6i8 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> (1011..(595) <223> RXN00833 <400> 63 agctttttgc atgtgtcata tcgtaccgtt tqcataggcc tgttcgcgct tggtgaacct tttctagcac caaaacaaaa ctctccctag tatggggtcc atg gct aaa aca cat 115 Met Ala Lys Thr His 1 ttt caa ggc aac gaa act gct acc tcc ggc gaa ctg cca cag gtc ggC 163 Phe Gin Gly Asn Giu Thr Aia Thr Ser Gly Giu Leu Pro Gin Val Gly 15 WO 01/00804 WO 0100804PCT/IBOO/00922 gac aac ctc gca Asp Asn Leu Ala ttc aac ctc Phe Asn Leu t cc Ser t cc Ser gca Ala ctt Leu gtc Val1 atc Ile atc Ile gag t ca Ser gt t Val1 gca Ala cca Pro ac Thr gtg Val1 gtc Vai 135 atc aag Lys ga c Asp gca Ala ttc Phe cca Pro ct C Leu 120 gt c Val1 ttc ttc cag Phe Gin ggc gtt Gly Val ctq gaa Leu Giu ctg. ggc Leu Gly tcc gca Ser Ala ggc tca Gly Ser gaa aac Giu Asn gaa cct Giu Pro ggC Gly tgt Cys 60 aac Asn cgt Arg ttc Phe cca Pro ggc Gly 140 gtc Val1 aag Lys aca Thr acc Thr tgc Cys tcc Ser 110 aag Lys gtt Val Asn Thr Glu Leu aac acc gaa ctg ggc gag qtc Gly Glu Val ctg aac Leu Asn cgc aag Arg Lys tgc atc Cys Ile qaa qgc Glu Giy gat tac gac gct gca ctt gct. ggg ctg aac Asp Tyr Asp Ala Ala Leu Ala Gly Leu Asn Glu Ilie Phe Thr 150 taatttactt cgctcagggg aat <210> 64 <211> 165 <212> PRT <213> Corynebacterium giutamicum <400> 64 Met Ala Lys Thr His Phe Gin Gly Asn Giu Thr Ala Thr Ser Gly Giu 1 5 10 Leu Pro Gin Val Gly Asp Asn Leu Ala Giu Phe Asn Leu Val Asn Thr 25 Giu Leu Gly Glu Val Ser Ser Lys Asp Phe Gin Gly Arg Lys Leu Val 40 Leu Asn Ile Phe Pro Ser Vai Asp Thr Gly Val Cys Ala Thr Ser Val 55 Arg Cys Glu Gly Leu Th r 145 Leu WO 01/00804 Lys Phe Asn Glu Ile Ser Lys Asp Gly Ile Giu Asn 100 Glu Asp Asn Gly 115 Ala Arq Ser Val 130 Gin Leu Val Asp Ala Gly Leu Asn 165 Giu Gly Al a Ser Asn Pro 155 PCT/IBOO/00922 <210> <211> 879 <212> DNA <213> Corynebacteriwn glutamicum <220> <221> COS <222> (856) <223> RXN01676 <400> aqttaeagct tttctcggtg gcacactcgc gctacttagc accageattt tttgcatcct cagtgggtgc tggcccgcgc gtt Val1 ggt Gly atc Ile t tc Phe ctg Leu gca Al a ctc Leu t cg Ser ttc Phe gCC Ala cta Leu ctg Leu ctg Leu gga Gly acc Thr ctt Leu 15 ate Ile ate Ile gca Al a ggt Gi y ccttgtgccg cactectttt atg atec tt cac ggt Met Ile Leu His Gly 1 gtg cca ctt ggc ctt Val Pro Leu Giy Leu caa cgc cag ace atc Gin Arg Gin Thr Ile gqt ttt gte cag atc Gly Phe Val Gin Ile cca gga tta gat cgt Pro Gly Leu Asp Arg gga aag agc ttt tta Gly Lys Ser Phe Leu 115 163 211 259 307 355 WO 01/00804 WO 0100804PCT/IBOO/00922 cta gga Leu Gly ggc gcc Gly Ala gca etc Ala Leu gct ati Ala Ile 135 etc cgc Leu Arg 150 tct gte Ser Val tee aeg Ser Thr cag ate Gin Ile gac ate Asp Ile 215 aac ass Asn Lys 230 atg Met gt t Val1 att Ile 120 gca Ala ggC Gly att Ile sac Asn tg Trp 200 gca Ala cga Arg ace Thr ct t Le u 105 t tg Leu gcg Ala cgg9 Arg age Se r ggc Gly 185 cta Leu ttg Leu eaa Gin agt Ser act Th r agt S er etc Leu gas Giu ggt Gi y 170 ct t Leu eag Gin ate Ile aag Lys agt S er t tg Leu get Ala tgg Trp t tc Phe 155 gcc Ala gte Val gas Gi u att Ile cga Arg 235 at t Ile get Ala tat Tyr gc Aia 140 acc Thr ct g Leu age Se r gee Ala gte Val 220 aaa Lys gee Ala gee Ala ggt Gly 125 ass Lys tte Phe ate Ile atg Met a Thr 205 gee Ala gas ggt Gly ace Th r 110 geg Ala etc Leu t tg Leu ate Ile ceg Pro 190 tte Phe get Ala gas tt t Phe 95 agt Ser gga Gly gga Gly gge Gly get Al a 175 gag Glu tea Ser ggc Gly get tgt Cys gga Gly a tg Met eag Gin agg Arg 160 gte Val1 etc Leu etc Leu t tg Leu cag tee Ser sac Asn gtg ValI cgt Arg 145 cag Gin gga Gly gtt Val ggg Gly tte Phe 225 cga ces Pro ate Ile 115 ccc Pro cag Gin eac His etc Le u atg Met 195 cca Pro tac Tyr ass ate etc Ile Leu 100 ace tea Thr Ser ctg atg Leu Met cag atg Gin Met att gtt Ile Val 165 ttt tgg Phe Trp 180 gac ace Asp Thr etc ttt Leu Phe ttc tgg Phe Trp gsa agt Glu Ser 245 Glu Giu Ala Gin Arg Pro Lys 240 tgg gtt att sac cet ege taattattag ttttggageg agg Trp Val Ile Asn Pro Arg <210> 66 <211> 252 <212> PRT <213> Corynebacterium glutamicum <400> 66 Met Ilie Leu His Gly Vai Val Phe Tyr Ala Gly Leu Leu Val Leu Leu 1 5 10 Val Pro Leu Gly Leu Gly Ala Gly Ilie Leu Gly Glu Leu Phe Ile Thr WO 01/00804 WO 0100804PCT/IBOO/00922 25 Gin Arg Gin Thr Ilie Ile Val Val Ser Ser Ile Val Le Ile Ile Leu 40 Gly Phe Val Gin Ile Phe Gly Giy Giy Phe Asp Phe Giy Lys Ala Leu 55 Pro Gly Leu Asp Arg Leu Gin Ser Lys Ala Thr Val Thr Ser Gly Leu 70 75 Gly Lys Ser Phe Leu Leu Gly Met Thr Ser Ser Ile Ala Gly Phe Cys 90 Ser Gly Pro Ile Leu Gly Ala Vai Leu Thr Leo Ala Ala Thr Ser Giy 100 105 -110 Asn Ser Ilie Thr Ser Ala Leo Ile Leu Ser Ala Tyr Giy Ala Gly Met 115 120 125 Val Leu Pro Leo Met Ala Ilie Ala Ala Leu Trp Ala Lys Leu Giy Gin 130 135 140 Arg Gly Gin Gin Met Leu Arg Gly Arg Giu Phe Thr Phe Leu Gly Arg 145 150 155 160 Gin Trp His Ile Val Ser Val Ile Ser Gly Ala Leu Ile Ile Ala Val 165 170 175 Gly Ile Leo Phe Trp Ser Thr Asn Giy Leo Vai Ser Met Pro Glu Leo 180 185 190 Val Pro Met Asp Thr Gin Ilie Trp Leu Gin Glu Ala Thr Phe Ser Leu 195 200 205 Gly Ser Pro Leo Phe Asp Ilie Ala Leo Ile Ile Vai Ala Ala Giy Leo 210 215 220 Phe Leo Tyr Phe Trp Asn Lys Arg Gin Lys Arg Lys Glu Gbu Ala Gin 225 230 235 240 Arg Pro Lys Glu Ser Gly Trp Val Ile Asn Pro Arg 245 250 <210> 67 <211> 744 <212> DNA <213> Corynebacteriom qiotamicum <22 0> <221> CDS <222> (101)..(721) <223> RXN00380 <400> 67 caggcaatgc gacctcgcct cagtgacatc cttggtgttc caagacgatc aaattgtcgg WO 01/00804 PCTIBOOIOO922 egt ttg acc aaa 115 Arg Leu Thr Lys cgtgcattae aacgaaccag cteaggagat ttgatcactc gtg Val1 1 eta gca Leu Ala gcc tgc Ala Cys gga acc Gly Thr gac gag Asp Glu atg gaa Met Giu gtc atc Val Ile ice gat Ser Asp ggc gac Gly Asp tcc cgc Ser Arg 135 cca agc Pro Ser 150 git ccc Val Pro ege ccc Arg Pro gca Ala age Ser ttC Phe 420 get Al a gag Glu etc Leu gati Asp ace Thr 120 gac Asp att Ile gca Ala gca Al a aca Thr agt S er caa Gin ga e Asp ggc Gly aat Asn etc Leu 105 cct Pro ate Ile tac Tyr tcg Se r gea Al a 185 ate Ile gac Asp tte Phe egt Arg aca Thr geg Ala cag Gin ggt Gly gee Ala gati Asp gig Val1 170 gig Val ggc tge Gly Cys agt ace Ser Thr eac tee His Ser eaa caa Gin Gin 60 cag ate Gln Ile 75 tgg gg Trp Gly ait ate Ilie Ile ggc ace Gly Thr eaa gac Gin Asp 140 eca eca Pro Pro 155 ate eca Ile Pro ttc tig Phe Leu gig aca Val Thr get ggt Aia Gly 30 eeg gat Pro Asp etc ccc Leu Pro aac ctg Asn Leu eag tgg Gin Trp cat gag His Glu 110 gig tig Val Leu 125 itt gte Phe Val itt atg Phe Met ace ace Thr Thr ege gaa Arg Glu i190 etc Leu 15 act Thr gga Gly ga e Asp tct Ser tgt Cys 95 qaa Glu ggt Gly ace Thr aea Thr ate Ile 175 gte Vali gga di y get Ala atg Met ggt Gl y tt Phe ceg Pro caa Gin aat Asn aarz As n 145 gca Al a ct g Leu tee gcg Ala get Al a at i Ile ga t Asp aac Asn ege Arg gee Al a 115 egt Arg ct Leu etc Leu aaa Lys gat eta gia Leu Val gte gge Val Gly tic tae Phe Tyr ice etc Ser Leu eaa gt Gin Val ice gaa Ser Glu 100 gga aac Gly Asn gat tac Asp Tyr gat tac Asp Tyr ggt ggt Gly Gly 165 cag cae Gin His 180 gtg ttg Val Leu Thr Ser Lys Asp 195 gat gti geg Asp Val Ala 200 ttg eca ttg gia gat Leu Pro Leu Vai Asp 205 gag gee taaatgietg agaitgtggt Glu Ala WO 01/00804 agc <210> 68 <211> 207 <212> PRT <213> Corynebacterium glutamicum (400> 68 Val Arq Leu Thr Lys Leu Ala Ala Thr PCT/IBOO/00922 744 Leu Val Phe Ser Gin Ser 100 Gly Asp Asp Gly Gin 180 Ala Gi y Asp Met Val1 Se r Gi y Ser Pro 150 Val Arg Ser Ser Phe Gin Ala Asp Glu Gly Leu Asn Asp Leu 105 Thr Pro 120 Asp Ile Ile Tyr Ala Ser Ala Ala 185 Cys Thr Se r Gin Ile GI y Ile Th r Asp 140 Pro Pro Leu Ser Lys Asp 195 Val Leu Asp Val Ala 200 Leu Pro Leu Val Asp Glu Ala 205 (210> 69 <211> 495 <212> DNA <213> Corynebacterium glutamicum <220> <221> COS <222> (472) WO 01/00804 <223> RXN00937 <400> 69 agctgccggt caatgaagaa aatccttggc cgggaataac tctatatata gaccttacaa atcttgaacg gagattctta PCT/IBOO/00922 tacagtccgc tgaaagttgg atg gca Met Ala 9ta Val1 ct c Leu cca Pro aag Lys cag Gin cgc Arg cag Gin acc gaa Thr Glu gta gac Val Asp acc tac Thr Tyr ctt gat Leu Asp tcc atc Ser Ile gaa gcc Giu Ala gtt aag Val Lys gaa Glu gca Ala gag Giu acc Thr c ca Pro ggc Gly gca Al a 105 aca ttt Thr Phe tgg gca Trp Ala aag gtt Lys Val gaa gca Giu Ala act ctg Thr Leu 75 acc atg Thr Met ctc gac Leu Asp gag GI u tcc Ser tcC Ser aac Asn 60 atg Met cca Pro a tg a gc Ser tgg Trp gaa Giu 45 cag Gin gtt Val gct Ala gat aca qtt Thr Val 15 tgc gga Cys Gly 30 acc cac Thr His ggc ctg Gly Leu ttc cgc Phe Arg cct gca Pro Ala 95 gac gtt acc Thr cct Pro acc Th r gct Ala gac Asp 80 ctg Leu cgt 1 9gC Gly tgc Cys gac Asp gca Ala ggc Gly ga t Asp cgc gac Asp cgc Arg gca Ala gca Ala atc Ile gat Asp cag acc atc gat Thr Ile Asp gga att gtc Gly Ile Val cag ttc gcc Gin Phe Ala acc ttc gcc Thr Phe Ala ctg cag atc Leu Gin Ile atg gtc tac Met Val Tyr ctg gtc aac Leu Val Asn 100 gtc gca gag Val Ala Glu 115 115 163 211 259 307 355 403 451 Met Asp Asp 110 Val Arg Arg Gin cag cag ggt tct Gin Gin Gly Ser 120 gca gag gca Ala Giu Ala taagcttcca attgtgtttt ggt <210> <211> 124 <212> PRT <213> Corynebacterium giutamicum <400> Met Ala Thr Ilie Asp Val Thr Giu Glu Thr Phe Giu Ser Thr Val Thr 1 5 10 Gly Asp Gly Ilie Val Leu Val Asp Ala Trp Ala Ser Trp Cys Gly Pro 25 Cys Arg Gin Phe Ala Pro Thr Tyr Glu Lys Val Ser Glu Thr His Thr 40 Asp Al a Gly Asp Arg WO 01/00804 Ala Thr Phe Ala Lys Leu Asp Thr Giu Ala Asn Gin Gly Leu Ala 55 Ala Leu Gin Ile Gin Ser Ile Pro Thr Leu Met Val Phe Arg Asp 70 75 Ile Met Val Tyr Arg Glu Ala Gly Thr Met Pro Ala Pro Ala Leu 90 Asp Leu Val Asn Gin Val Lys Ala Leu Asp Met Asp Asp Val Arg 100 105 110 Gin Val Ala Giu Gin Gin Gly Ser Ala Giu Ala 115 120 PCTIIBOO/00922 <210> 71 <211> 990 <212> DNA <213> Corynebacteriun giutamicum <2 <221> CDS <222> (101)..(967) <223> RXN02325 <400> 71 cagagatttg aagatggaga ccaaggctca aagggaatcc tgcacccgtc taatgaaaat cattactatt aggtgtcatg gat tce Asp Ser ctc caa Leu Gin gtt gee Val Ala acg cag Thr Gin ctg ctg Leu Leu gca ggt Ala Gly t ca Se r gag Giu ata Ile t ca Se r aca Thr aaa Lys c ca Pro aaa Lys acg Thr aaa Lys ttt Phe 9gg Gly ct g Le u gt c ValI gtg Vai aag Lys 60 gat Asp cgc Arg ga t Asp ace Thr gag Glu ttg Leu ga t Asp 15 gca Al a tea Ser gtg Val aaa Lys gcg Al a 95 atgccgtctt ggtttaatac atg gac cat gca cac Met Asp His Ala His 1 gag gte act ggc cag Giu Val Thr Gly Gin ccg cac gaa ggg aag Pro His Giu Gly Lys atg gag cae ace ate Met Giu His Thr Ile etc att ggt cac tce Leu Ile Giy His Ser att etg cac ttt eag Ilie Leu His Phe Gin gtt gat cet gat egc Val Asp Pro Asp Arg 100 115 163 211 259 307 355 403 ttt tet gta Phe Ser Val WO 01/00804 WO 0100804PCT/IBOO/00922 agt gca gat gtg Ser Ala Asp Val gtt gcc aga ttt agg cca aaa cag att ccg gtg gca Val Ala Arg Phe Arg Pro Lys Gin Ile Pro Val Ala tac T yr a ag Lys atc Ilie 150 ctg Leu ttg Leu ca c Ais gag Glu gcg Ala 230 gcg Ala cgg Arg gtg Val1 gag Gi u 135 ccc Pro tgg Trp gcg Ala gcg Ala gat Asp 215 ctg Leu ct c Leu atc Ile gtg Val1 120 ccg Pro aat Asn Cgg Arg t tg Leu gcg Al a 200 ccg Pro gcg Al a gcg Ala gtg Val 105 aaa Lys gtt Val1 gaa Giu gca Ala tat Tyr 185 gt g ValI atc Ilie gcg Ala cac His gag Glu 265 gat Asp gca Ala aaa Lys gcg Al a 170 gag Giu t cg Ser gag Giu gcg Ala ct t Leui 250 tt g Leu ggc Gly caa Gin gag Glu 155 gaa Giu cag Gin gta Val aag Lys gat Asp 235 gca Al a ctg Leu gcc Ala t gg Trp 140 ggg GI y ttg Leu ttg Leu t tg Leu tcg Ser 220 atg Met gca Al a aac Asn agc Ser 125 ctt Leu gac Asp gtg Val ccg Pro gcg Al a 205 cgc Arg tat Tyr cta Leu ttg Leu 110 att Ile gat Asp gt C Val1 aac As n cag Gin 190 C9g Arg cgg Arg g tg Val1 ttg Leu ttt Phe 270 gcg Al a cat His ga t Asp gcc Ala 175 gat Asp atg Met gat Asp ttg Leu cca Pro 255 gat Asp gag ttc Glu Phe ttt gtg Phe Val 145 aag caa Lys Gin 160 ggt gat Gly Asp gcg acg Ala Thr tct gtg Ser Vai cca gac Pro Asp 225 atg aat Met Asn 240 aaa ccg Lys Pro ccg ctg Pro Leu aac As n 130 tcg Ser ata Ile ttt Phe gtg Val1 gcg Al a 210 gat Asp cag Gin gag Glu gac ctc Leu gaa Glu ccg Pro gcg Ala 180 Cgg Arg cgg Arg aac As n gac Asp gcc Ala 260 gt C Asp Leu Val 275 ttg gaa atc agg gcg Leu Glu Ile Axg Ala 280 cag gtg ggg aat Gin Val Gly Asn 285 gca atg agc taagaaaaca Ala Met Ser ctttaaatat tct <210> 72 <211> 289 <212> PRT <213> Corynebacterium glutamicum <400> 72 WO 01/00804 WO 01/4)804PCT/IBOO/00922 Met Asp His Ala His Asp Ser Cys Ser Pro Thr Leu 1 5 10 Arg Arq Asp Leu Giu Pro Met Leu Ile Val1 Gin Phe Val1 145 Gin Asp Thr Val1 Asp 225 Asn Pro Val His Glu Ile Leu Asp Ilie Asn 130 Ser Ile Phe Val1 Ala 210 Asp Gin Glu Thr Glu His Giy His Pro Pro 115 Ser Arg Asp Arg Lys 195 Asp Val Pro Ala Gly Gin Gly Lys Thr Ile His Ser Phe Gin Asp Arg 100 Vai Ala Leu Asn Glu Thr Pro Arg 165 Ala Ala 180 Arg Ala Arg Gly Asn Lys Asp Thr 245 Aia Arg Leu Val1 Thr Leu 70 Ala Ser Tyr Lys Ile 150 Leu Le u His Glu Al a 230 Ala Irg Gin Aila Gin 55 Leu Gi y Al a Val1 Giu 135 Pro Trp Al a Ala.
Asp 215 Leu Leu Ile Pro Asn 40 Al a Pro Asn Asp Val1 120 Pro As n Arg Leu Ala 200 Pro kl a kl a fa 1 Giu 25 Ile Ser Thr Lys Val1 105 Lys Val Giu Ala Tyr 185 Val Ile Al a His Giu Lys Thr Lys Phe Gi y 90 ValI Asp Ala Lys Ala 170 Gi u Ser Giu Al a Leu 250 Leu Ala Lys Aia Gin 75 Arg Ala Gi y Gin Gi u 155 Giu Gin Val Lys Asp 235 Ala Leu ValI Val Lys Asp Phe Arg Al a Trp 140 Gly Leu Leu Leu Se r 220 Met Ala Asn *Asp *Thr Glu Leu Ser *Phe Ser 125 Leu Asp Val Pro Al a 205 krg Tyr Leu Leu Gly 285 Leu Ser Val1 Glu Val1 Arg 110 Ile Asp Val1 Asn Gin 190 Arg Arg Val1 Leu Phe Ala Se r Val1 Lys Al a Pro Ala His Asp Al a 175 Asp Met Asp Leu Pro 255 Asp Aia Asn Val Asp Ile Lys Glu Phe Lys 160 GI y Ala Se r Pro Met 240 Lys Pro 260 265 270 Asn Ala Met Leu Asp Leu Val Ala Leu Glu Ile Arg Ala Gin Vai WO 01/00804 WO 0100804PCT/IBOO/00922 <210> 73 <211> 900 <212> DNA <213> Corynebacieriun glutarnicum <220> <221> CDS <222> (877) <223> RXN01837 <400> 73 cccccatcai tccctcaagg tgtgaagata cggttaggat agaaaaqaat ttttitgacg ttggacatic tcaaaatcaa gtagcaaggg atcaaactct gaa Glu cgg Arg ctg Leu cgc Arg gca Ala cic Leu aag Lys gig Val1 gati Asp cga cgc Arg Arg gac cgc Asp Arg gci gtc Ala Val agc acc Ser Thr gag acc Giu Thr ggc gac Gly Asp gat gic Asp Val acc gtc Thr Val 120 cgc tcc Arg Ser 135 caa Gin aaa Lys aic Ile gaa C iu cct Pro tcc Se r tcc Se r 105 aac Asn gi a Val ca g Gin gaa Giu cig Leu gac Asp ga c Asp gig Val1 aag Lys cig Leu icc Ser gcg Ala aag Lys gii Vai gaa Glu iac Tyr 75 acd Thr cct Pro acc TIhr cci Pro ct i Le u acc Th r gi c Val1 gic Val1 60 cag Gin t gi Cys got Ala acc Thr tgt Cys 140 tcc Se r aag Lys gi i Val1 45 aic Ilie c ca Pro gag Gi u act Thr gcC Ala 125 acc Thr cag Gin cca Pro 30 9gc Gly acc Thr ctg Leu iac Tyr gaa Giu 110 cag Gin gic Val1 ctg Leu 15 cia Leu gg t GI y gc t Al a gcg Ala cca Pro 95 aac Asn ggc Gly aac Asn gag Giu acc Th r aic Ile gat Asp cig Leu 80 gat Asp gig Val1 aac Asn gct Ala gt g Val1 1 aaa Lys gig Vali i gg T rp, gaa Glu 65 acc Thr gci Ala cca Pro aic Ile gt Val 145 gaa Giu gi c Val1 iac Tyr 50 aca Thr cgc Arg 9gC Gly gca Ala ggC Gly 130 gag Giu aaa Lys 20 gci.
Aia gct Aia acc Thr acc Thr gci Ala 100 ggC Giy gaa Giu aig Met agi act aai aag Ser Thr Asn Lys agc Se r icc Ser acc Thr acc Thr gcg Ala icc Ser acc Thr cti Leu gci Al a 115 163 211 259 307 355 403 451 499 547 icc S er 150 gag ggc iac iac aac Giu Gly Tyr Tyr Asn gat act gic Asp Thr Val igc cac cgc atc acc acc: ict Cys His 160 Arg Ile Thr Thr WO 01/00804 ggc att tac gtt ctc cag tgc ggc Gly Ile Tyr Val Leu Gin Cys Gly 170 gqc cca ggg ttc agc ttc gcc aac Gly Pro Gly Phe Ser Phe Ala Asn 185 gac cta acc acc cca gtc atc tac Asp Leu Thr Thr Pro Val Ile Tyr 200 205 aac gct ggc gct gac acc aac ggg Asn Ala Gly Ala Asp Thr Asn Gly 215 220 gga ttc ccc act ggc acc gaa cta Gly Phe Pro Thr Gly Thr Glu Leu 230 235 aga agg cct tgc aac Cct cga cgc Arg Arg Pro Cys Asn Pro Arg Arg 250 tgaaggtgga accggcgacg gag <210> 74 <211> 259 <212> PRT <213> Corynebacterium glutamicum <400> 74 Val Ser Thr Asn Lys Glu Arg Arg 1 5 Lys Glu Ilie Lys Ser Arg Asp Arg Val Val Phe Ala Ser Leu Ala Val2 40 Trp Tyr Ala Ala Thr Arg Ser Thr C 55 Glu Thr Ser Thr Thr Ala Glu Thr E 70 Thr Arq Thr Thr Ala Leu Gly Asp S Ala Gly Glu Ala Ser Lys Asp Val S 1001 Pro Ala Thr Gly Thr Val Thr Val A 115 120 ga t Asp ga a Glu 190 gag Giu Ct C Leu cac His cat His cca Pro 175 tac Tyr cgc Arg cca Pro cta Leu cgc Arg 255 ggc Gly act Thr gcc Al a cga Arg cga Arg 245 PCT/1B00100922 643 691 739 787 835 Gln 25 Ile ;1u ~ro er :er 05 .sn Ala Lys Val Glu Tyr 75 Thr Pro Thr Leu Ser Thr Lys Val Val Val Ile Gin Pro Cys Giu Ala Thr Thr Ala 125 Gin Leu Pro Leu Gly Gly Thr Ala Leu Ala Tyr Pro Giu Asn 110 Gin Gly Gi u Thr Ile Asp Leu Asp Val1 As n Ile Val 145 Arg Ser Thr Thr Leu 225 Arg Ser WO 01/00804 Gly Met Glu 130 Glu His Met Ile Thr Thr Thr Gly Ala 180 Asp Glu Ala 195 Ile Ala Met 210 Pro Gin Leu Pro Asp His Trp His Leu Al a Ser 165 Gly Thr Al a Arg Arcj 245 Ser Gly Tyr Gi y Thr 200 Gi y Pro Pro Val1 Tyr Val1 Phe 185 Thr Ala Thr Cys :aa ;In ;ca la 25 .tc ~eu tc he cc c Ser Tyr Leu 170 Se r Pro Asp Gly As n 250 gcc Ala a G1u aac k.sn Jcc Pro Asn 155 Gin Phe Val1 Thr Thr 235 Pro atc Ile ct C Leu t gc Cys gtc Val1 ggC Cys 140 Asp Cys Ala Ile As n 220 Giu Arg gaa Glu ctc Leu a cc Thr cac His cgc Th r Thr Gi y Asn Tyr 205 Gly Leu Arg cgc Arg gca Ala acc Thr caa Gin gac PCTJIBOO/00922 Val1 Val Asp Glu 190 Giu Leu His His gaa Glu gct Ala t cc Ser atc Ile gca Asn Cys Pro 175 Tyr Arg Pro Leu Arg 255 ggC Gi y gac Asp cca Pro ctg Leu gac <210> <211> 741 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> <223> RXN01926 <400> ctg cga agc ttc tac acc cca ga Leu Arg Ser Phe Tyr Thr Pro Giu( 1 5 gtc tgg aaa gcc gcc acc gsa gaac Val Trp Lys Ala Ala Thr Glu Giu gcc gtc cac gac cag gaa ctc ttc c Ala Val His Asp Gin Glu Leu Phe L 40 atc ttc gcc tcc gcg atg ctc aac t Ile Phe Ala Ser Ala Met Leu Asn P 55 acc ctc tgc caa ctc gca cca tcc c WO 01/00804 WO 0100804PCT/IBOO/00922 Thr Leu Cys Gin Leu Ala Pro Ser Pro Ala Gly Arg Asp Ala Asp Pro 70 75 so aaa Lys ac Thr aaa Lys ttc: Phe tcC Se r 145 gaa Glu ctc Leu c ca Pro t ca Ser tcC Ser 225 ct C Leu gac Asp ca C His 115 cgc Arg aaa Lys gcc Al a cca Pro cca Pro 195 ggC Gly gg t Gly gaa gCC: Giu Ala ttC tcc Phe Ser 100 cgc gat Arg Asp ggc atg Gly Met tac gcc Tyr Ala tt cCC Phe Pro 165 ggc gac Gly Asp 180 aaa ttc Lys Phe aaa tac: Lys Tyr qtc gtC Val Val gcc acc Ala Thr ggC gtc Gly Val acc ctc Thr Leu caa gtc Gin Val 135 ctc acc Leu Thr 150 ggc gac: Gly Asp acc atc: Thr Ile gcg cca Ala Pro aaa cag Lys Gin 215 cag atc Gin Ile 230 gca Ala ttC Phe 105 ttc: Phe cac His ttC Phe gt c Val gaa Giu 185 cac His cgc Arg aag Lys aac cca ggt cat ggc cgg tgt Asn Pro Gly His Gly Arg Cys 245 <210> 76 <211> 247 <212> PRT (213> Corynebacterium giutamicun <400> 76 Leu Arg Ser Phe Tyr Thr Pro Giu Gln Ala Ile Giu Arg Giu Gly Asp 1 5 10 WO 01/00804 WO 0100804PCT/IBOO/00922 Val Trp Lys Ala Ala Thr Glu Glu Ala Glu Leu Leu Ala Ala Asp Gly 25 Ala Val Ile Phe Thr Leu Lys. Ala Thr Asp Lys Asn Phe Asp 130 Ser Thr 145 Glu Thr Leu Ala Pro Met Ser Leu 210 Ser Glu 225 Asri Pro His Ala Cys Leu Asp His 115 Arg Lys Al a Pro Pro 195 Gly Gly Gly Asp Ser Gln Glu Phe 100 Arg Gly Tyr Phe Gly 180 Lys Lys Val His Gin Giu Leu Ala Met Leu 55 Leu Ala Pro Ala Ala Thr Ser Gly Val Asp Thr Leu Met Gin Val 135 Ala Leu Thr 150 Pro Gly Asp 165 Asp Thr Ile Phe Ala Pro Tyr Lys Gin 215 Val Gln Ile 230 Gly Arg Cys 245 Phe 40 Asn Ser Ser Val1 Ala 120 Thr Val1 Ile Phe Glu 200 Phe As n Giy Al a Met Lys Met Ser Gly Gly 170 Gly Phe Lys Thr His Arg Asp Gin Val1 Ser 140 Thr Val1 Lys Ile Leu 220 Thr Gin Asp His Ala Val1 125 Gi y Arg Asn Ile Leu 205 Glu Leu Lys Asn Asp Leu Arg Gly Asp Ala <210> 77 <211> 478 <212> DNA <213> Corynebacterium giutamicum <220> <221> CDS <222> (101)..(478) <223> RXN02002 <400> 77 WO 01/00804 PCTABOO/00922 aagtggcaaa aaacgtttca agcaggcaac gccggcgtac aacttcgctg agctggggcg attatggccc agcgcccaca acccgctatt cttaataccc atg agc aac qcc aat 1 Met Ser Asn Ala Asn tcc Ser atc Ile ctg Leu ggC Gly ggc Gly ggc Gly cac His ga c Asp gca Ala cat H is cgc Arg atc Ile cac His gcc Ala acc Th r cac His gca Al a aaa Lys tcc Ser gca Ala gac Asp acc gcc qCC Thr Ala Ala ccc gac 9CC Pro Asp Ala cac atc atc His Ile Ile gcc acc gtt Ala Thr Val atc gcc tcc Ile Ala Ser 75 ggc gag ccc Gly Giu Pro ttc tcc gaa Phe Ser Giu 105 gca Ala aaa Lys ga a Glu 45 ga c Asp gca Ala atg Met a cc Thr cg c Arg 15 acc Thr ggc Giy atg Met caa Gin aac Asn 1 a ga Arg acc Thr acc Th r atg Met gag Glu gtg Vali aca Th r gag Glu cac His 50 gaa Glu t ac Tyr gac Asp gta Val1 gcg Ala gca Al1a cgc Arg gaa Glu ggc Gly ga c Asp cgc gtc ctc atg gcc gtc Arg Val Leu Met Ala Val gca gca qtc atg ctt atg cac tcc gtc Ala Ala Val Met Leu Met His Ser Val 120 125 <210> 78 <211> 126 <212> PRT <213> Corynebacteriun glutamicum <400> 78 Met Ser Asn Ala Asn Ser Asp Thr Thr Ala Ala (flu Ala His Arg Arg 1 5 10 Arg Thr Phe Aia Val Ile Ala His Pro Asp Ala Gly Lys Ser Thr Leu 25 Thr Glu Aia Leu Ala Leu His Ala His Ile Ile Ser Giu Ala Gly Ala 40 Thr His Gly Lys Ala Giy Arg Lys Ala Thr Val Ser Asp Trp Met Glu 55 WO 01/00804 Met Giu Lys Asp Arg Gly Ile Ser Ile Ala Ser Ser Ala Leu Gin Phe 70 75 Glu Tyr Ala Pro Giu Gly His Ala Gly Glu Pro Phe Met Ile Asn Leu 90 Val Asp Thr Pro Gly His Ala Asp Phe Ser Glu Asp Thr Tyr Arg Val 100 105 110 Leu Met Ala Val Asp Ala Ala Val Met Leu Met His Ser Val 115 120 125 PCT/IBOO/00922 <210> 79 <211> 1080 <212> DNA <213> Corynebacteriun giutamicun <220> <221> CDS <222> (101)..(1057) <223> RXN02736 <400> 79 cagaggatta cccagcgggt acgtggggtc caaagagcgc tgatgaaatg ctttcccgca acggtcacac ctggcgcagg ccataattta ggggcaaaaa atg atc ttt gaa ctt Met Ile Phe Giu Leu ceg Pro gaa Giu gt c Val1 gaa Glu gat Asp gac Asp gct Al a acc acc Thr Thr ggc acc Giy Thr gac tcc Asp Ser tcg cgc Ser Arg act gca Thr Ala ggt gct Gly Ala aag ctc Lys Leu 105 acc Th r ca g Gin gaa Giu gag Glu gaa Glu tcc Ser cag Gin caa Gin ace Thr gat Asp c ca Pro aaa Lys atg Met gtc Val1 att tcc Ile Ser acc ggc Thr Giy 30 gtc gct Val Ala 45 tct cgc Ser Arg qtt gac Val Asp atc ate Ile Ile gtc aca Val Thr 110 aag Lys 15 cga Arg gca Ala gtg Val1 gca Ala atg Met 95 cca Pro 1 ct a Leu ctc Leu acc Th r att Ile gtc Val ct C Leu t tg Leu act cga ctg Thr Arg Leu acc ctc atc Thr Leu Ile gag tcc acc Giu Ser Thr ttg gtg gtt Leu Val Val cgt atc ggt Arg Ile Gly aac gga cct Asn Gly Pro 100 ctt cct gac Leu Pro Asp 115 115 163 211 259 307 355 403 451 WO 01/00804 WO 0100804PCT/IBOO/00922 coo atc Pro Ile gac oca Asp Pro 135 gac cgt Asp Arg 150 gat aco Asp Thr gcc tcc Ala Ser ctg acc Leu Thr ttg gog Leu Ala 215 ccc acc: Pro Thr 230 cgC ctg Arg Leu gao got Asp Ala tog ctg Ser Leu gag ctt Glu Leu 295 gct Al a gga Gly gac Asp at g Met ttg Leu 185 gca Ala agg Arg cca Pro atc Ile acc: Th r 265 got Al a ca c His tgg tgg cca Trp Trp Pro ggt gaa Gly Giu 125 tca cca aag aat Cot tcc cag Ser Pro Lys Asn Pro Ser Gin 130 cgc Arg gca Al a a og Th r 170 gat Asp ago Ser cig Leu acc Thr gt t Val1 250 ct t Leu at Ile atg Met atc Ile cta Leu 155 tg Trp cac His ggc Gly aaa Lys gat Asp 235 ogc Arg cag Gin ggt Gly gat Asp aag Lys 315 gca Aia 140 gaa Giu gog Ala 0 ca Pro a gt Ser gt g Val1 220 gag Glu acc Thr gta Val cgt Arg cca Pro 300 ca a Gin gat Asp ogo Arg oca Pro aco Thr 205 Cc Pro ttt Phe aco Thr gag Glu cga Arg 285 gat Asp cga cgc Arg Arg ogt gtt Arg Val ctt acc Leu Thr 175 cac agc His Ser 190 tcg gig Ser Vai gig ato Val Ile ggt act Gly Thr ggc tcg Giy Ser 255 aig ccg Met Pro 270 agi gag Ser Giu tig ggc Leu Gly atc act gat Ile Thr Asp 145 gag aac tat Giu Asn Tyr 160 cag tgg cgg Gin Trp Arg gaa atc act Giu Ile Thr gat tig got Asp Leu*Ala 210 cgc gag gig Arg Giu Val 225 cca ctg cig Pro Leu Leu 240 ate ato atc Ile Ile Ile gaa tOO ggc Giu Ser Gly too: gao tgo Ser Asp Cys 290 tao cag cac Tyr Gin His got tig tac Ala Leu Tyr cac cca ggt His Pro Gly 165 gga ctt gtt Gly Leu Val 180 icc gig agg Ser Val Arg 195 goa ggC t9g Ala Gly Trp aca gat got Thr Asp Ala got ato cag Ala Ile Gin 245 aco ato tat Thr Ile Tyr 260 aat goc oca Asn Ala Pro 275 tig tot gag Leu Ser Giu gca cia too Ala Leu Ser 547 595 643 691 '739 '787 835 883 931 979 1027 1077 1080 ggo ttg too ago gte Giy Leu Ser Ser Vai 310 t gg <210> ctg gaa aco gic Leu Giu Thr Val taaggagaaa tacaacaota WO 01/00804 <211> 319 <212> PRT <213> Corynebacterium glutamicum PCT/IBOO/00922 <400> Met Ile Phe Glu Leu Pro Asp Thr Thr Thr Gin Gin Ile Ser Lys Thr 1 Leu Leu Thr Ile Val± Leu Leu Lys Thr 145 Asn Trp Ile Leu Glu 225 Leu Ile Thr Thr Glu Leu Arg Asn Leu Asn 130 Asp Tyr Arg Thr Aia 210 Val Leu Ie Arg Leu Ser Val1 Ile Gly Pro 115 Pro Ala His Gly Ser 195 Aia Thr Aia Thr Leu Ile Thr Val1 Gi y Pro 100 Asp Se r Leu Pro Leu 180 Val Gly Asp Ile Ile 5 Arg ValI Asn GI y Gi y Val1 Tb r Gin Tyr Gly 165 Val Arg Trp Ala Gin 245 Tyr IZ Git Val Giu Asp 70 Asp Ala Pro Asp Asp 150 Asp Al a Leu Leu Pro 230 krg ~sp 1Ser *Thr Ala 55 Lys *Ala Asp Ilie Pro 135 Arg Thr Se r Thr Ala 215 Thr Leu Ala Gly Asp Ser Thr cfly Lys Val1 120 Ile Asp Asp Se r Gly 200 Arg Val Glu HIis Thr 25 Ser Arg Ala Ala Leu 105 Ala Gi y Asp Met Leu 185 Ala Arg Pro Ile Thr 265 Gin Glu Gi u Gi u Ser 90 Gin Trp, Arg Ala Thr 170 Asp Ser Leu Thr ValI 250 Leu ValI Ser His Asn Giu Tyr T rp Ile Leu 155 Trp His Gly Lys Asp 235 Arg Gin Thr Asp Pro Lys Met Val1 Pro Ala 140 Glu Ala Pro S er Val1 220 Glu Thr Val1 Thr Val1 Se r ValI Ile Val1 Gly 125 Gin Asp Arg Pro Thr 205 Pro Phe Thr Glu Gly Ala Arg Asp Ile Thr 110 Glu Arg Arg Leu His 190 Se r Val1 Gly Gi y Met Arg Al a Val1 Al a Met Pro S er Arg Val1 Thr 175 Ser Val Ile Thr Se r 255 Pro 260 270 Ser Gly Asn Ala Pro Ser Leu Val Ala Ile Gly Arg Arg Ser Glu Ser WO 01/00804 275 280 285 Asp Cys Leu Ser Giu Glu Leu Arg His Met Asp Pro Asp Leu Gly Tyr 290 295 300 Gin His Ala Leu Ser Gly Leu Ser Ser Vai Lys Leu Giu Thr Val 305 310 315 <210> 81 <211> 331 <212> DNA <213> Corynebacterium glutamicun <220> <221> CDS <222> (301) <223> RXS03217 <400> 81 tctgtgaagg tagatggttt gacgaggagt tccaacgact cggacgctgg tgaatcat tggcgaacgt agcatcacct gattaggaaa aggtacaaat atg gca cag ggt act PCT/IBOO/00922 Ic 115 163 211 259 301 331 Met Ala Gin Gly Thr 1 gtg aaa tgg ttc aac ggc gaa aag gga ttt ggt ttc atc gct ccc: aac Val Lys Trp Phe Asn Gly Glu Lys Gly Phe Gly Phe Ile Ala Pro Asn 15 gat ggc tcc gca gat ctc ttc gtc cac tac tct gag att cag ggc tcc Asp Gly Ser Ala Asp Leu Phe Val His Tyr Ser Glu Ile Gin Gly Ser 30 ggt ttc cgt aat ctt gag gaa aac cag cca gtt gaa ttt gag gtc ggc Gly Phe Arg Asn Leu Giu Giu Asn Gin Pro Val Giu Phe Giu Val Gly 45 gag ggc gcc aag ggc cca cag gct cag cag gtt cgt gct ctc Giu Giy Ala Lys Gly Pro Gin Ala Gin Gin Val Arg Ala Leu 60 taagctctaa ctgctagcta aaaattccgc <210> 82 <211> 67 <212> PRT <213> Corynebacteriun giutanticum <400> 82 Met Ala Gin Gly Thr Val Lys Trp Phe Asn Gly Giu Lys Gly Phe Giy 1 5 10 Phe Ile Ala Pro Asn Asp Gly Ser Ala Asp Leu Phe Val His*Tyr Ser 25 WO 01/00804 Giu Ile Gin Gly Ser Gly Phe Arg Asn Leu Glu Glu Asn Gin Pro Val 40 Glu Phe Giu Val. Giy Giu Gly Ala Lys Gly Pro Gin Ala Gin Gin Val 55 Arg Ala Leu <210> 83 <211> 324 <212> DNA <213> Corynebacterium giutamicum <220> <221> CDS <222> (301) <223> FRx.A01917 <400> 83 tctgtgaagg tagatggttt gacgaggagt tccaacgaet eggacgctgg tgaatcat tggcgaacgt agcatcacct gattaggaaa aggtacaaat atg gca cag ggt act PCT/IBOO/00922 gc 115 163 211 259 301 324 Met Ala Gin Gly Thr 1 gtg aaa tgg ttc aac qgc gaa aaq gga ttt ggt ttc ate get ccc aac Val Lys Trp Phe Asn Gly Glu Lys Gly Phe Gly Phe Ile Ala Pro Asn 15 gat ggc tcc gca gat ctc ttc gtc cac tac tct gag att cag ggc tc Asp Gly Ser Ala Asp Leu Phe Val His Tyr Ser Giu Ile Gin Gly Ser 30 ggt ttc cgt aat ctt gag gaa aac cag cca gtt gaa ttt gag gtc ggc Gly Phe Arg Asn Leu Giu Glu Asn Gin Pro Val Glu Phe Glu Val Gly 45 gag ggc gcc aag ggc cca cag get cag eag gtt egt get etc Glu Gly Ala Lys Gly Pro Gin Ala Gin Gin Val Arg Ala Leu 60 taagctctaa ctgctageta aaa <210> 84 <211> 67 <212> PRT <213> Corynebacterium giutamicum <400> 84 Met Ala Gin Gly Thr Val Lys Trp Phe Asn Gly Giu Lys Gly Phe Gly 1 5 10 Phe Ile Ala Pro Asn Asp Gly Ser Ala Asp Leu Phe Val His Tyr Ser 25 WO 01/00804 Giu Ile Gin Gly Ser Gly Phe Arg Asn Leu Giu Giu Asn Gin Pro Val 40 Giu Phe Giu Val Gly Glu Gly Ala Lys Gly Pro Gin Ala Gin Gin Val 55 Arg Ala Leu PCT/IBOO/00922 <210> <211> 504 <212> DNA <213> Corynebacterium giutamicum <220> <221> CDS <222> (481) <223> RXA02184 <400> tttaccgcga tgcttgcggt gtataataat ttcttctggt caaaaatagt tgatcaattt gaatcagcat atgaattagg aatgaaagtg gtgaggacaa gtg cct gtc gga aca Val Pro Val Gly Thr gtg Val1 ggt Gi y acc Thr cgt Arg agg Arg tct Se r aaa aag Lys ggt GI y ga a Glu a ag Lys Cot Arg ga c Asp ggg tgg Trp ga a Giu t tg Leu goc Gi y cca Pro Ct C Leu caa tac Tyr Oat Asp cac His cct Pro cag Gin atc Ile tac gac Asp tgc Cys aag Lys ca a Gin cac His acg Thr ccg Oco Al a ttc Phe gga Gly gca.
Ala aaa Lys 75 ct Leu gag gag Giu gt a Val1 cag Gin Ct t Leu 60 tac Tyr cta Leu cac cot Arg ggt Gly cga Arg 45 cga Arg a ag Lys gaa.
Glu aaa got Giy aag Lys 30 at c Ile ata.
Ile cca Pro agi Se r Oct t tc Phe 15 ca a Gin oat Asp aag Lys ga a Giu gga Gly 95 qga goc Gly gta Val1 ttt Phe att Ile gag Giu 80 gtg Vai
I
tt Phe ct t Leu gac Asp cti Leu ctc Leu caa Gin cag gic Val
CCC
Pro tc Phe gaa Glu aac Asn cca Pro gt a icc aat Ser Asn 20 aag gga Lys Gly 35 gCC gca Ala Ala act cca Thr Pro gga atg Gly Met goc ct Gly Leu 100 gca gaa cca Pro gtc Val goc Gly CgC Arg atc Ile gcc Ala at t 163 211 259 307 355 403 451 Lys Gly Gin Tyr 105 Pro Giu His Lys Ala Gly Aia Gin Val Ala Giu Ile 110 115 cit cgc gtt gtt gc aag gag ctt gao tct. taaaacaata aggagaggat WO 01/00804 Leu Arg Val Val Ala Lys Giu Leu Giu Ser 120 125 ccg <210> 86 <211> 127 <212> PRT <213> Corynebacterium glutamicum <400> 86 Val Pro Val Gly Thr Val Lys Trp, Tyr Asp 1 5 Phe Val Ser Asn Pro Giy Gly Giu Asp Cys Leu Pro Lys Gly Val Thr Glu Leu His Lys Asp Phe Ala Ala C-iy Arg Lys Gly Pro Gin Leu Glu Thr Pro Arg Arg Arg Pro Gin His Leu Asn Gly Met Ile Ser Asp Leu Ile Thr Gin Pro Gly Leu Ala Lys Gly Gin Tyr Pro 100 105 Gin Val Ala Giu Ile Leu Arg Val Vai Ala 115 120 PCT/1B00100922 504 <210> 87 <211> 324 <212> DNA <213> Corynebacterium giutamicum <220> <221> CDS <222> (301) <223> RXA00810 <400> 87 tcggcgttcg ttcaagaaac ggccagatgt tgctgttcga gctcatgcaa gagtggaaca tcgaacccgg tagtaattcc aatcagtaaa ggtaagacaa atg gca cag ggc act 115 Met Ala Gin Gly Thr 1 gtt aag tgg ttc aac cca gag aag ggc ttc ggc ttc atc get cct tcc 163 Val Lys Trp Phe Asn Pro Glu Lys Gly Phe Gly Phe Ile Ala Pro Ser 15 WO 01/00804 gac gga tcc get gac gtt ttc gte cac tac tce gag atc gag ggc aac Asp Giy Ser Ala Asp Val Phe Val His Tyr Ser Glu Ile Giu Gly Asn 30 ggc tte egt ace etc gag gag aac eag etc gtc gag tte gaa ate ggc Gly Phe Arg Thr Leu Giu Glu Asn Gin Leu Vai Glu Phe Giu Ile Gly 45 gag ggc get aag ggc ctt cag get cag gct gtt cgt gca atc Giu Gly Ala Lys Gly Leu Gin Ala Gin Ala Val Arg Ala Ile 60 taattgeatc tgagttcgaa ace <210> 88 <211> 67 <212> PRT <213> Corynebacterium glutamicum <400> 88 Met Aia Gin Gly Thr Val Lys Trp Phe Asn Pro Giu Lys Gly Phe Gly 1 5 10 Phe Ilie Ala Pro Ser Asp Gly Ser Ala Asp Val Phe Val His Tyr Ser 25 Giu Ile Giu Gly Asn Giy Phe Azg Thr Leu Giu Glu Asn Gin Leu Val 40 Glu Phe Giu Ile Gly Glu Gly Ala Lys Gly Leu Gin Ala Gin Ala Val 55 Arg Ala Ile PCT/IBOO/00922 211 259 301 324 <210> 89 <211> 1017 <212> DNA <213> Corynebacterium glutamiewn <22 0> <221> CDS <222> (994) <223> RXA01674 <400> 89 eggcgtcgat tccagaaggt ttgtagacat gcttcaaggt tgcgctaatt gaaaagaaeg cggtagacgg tactttcata tecacecata taatgttgat atg gat aat ggg tgg 115 Met Asp Asn Gly Trp 1 ceg aac etg eaa act etc gca etc ttt gtg geg att gtg gaa gag ggg 163 Pro Asn Leu Gin Thr Leu Ala Leu Phe Val Ala Ile Val Giu Glu Gly WO 01/00804 WO 0100804PCT/IBOO/00922 aqc otc ggt gec Ser Leu Gly agt cgg gct Ser Arg Ala gta cgt cat Val Arg His gtt gag cat Val Giu His tgg gtg aca Trp Val Thr gcc agt atg Ala Ser Met atg cgo acg Met Arg Thr 120 tct tct caa Ser Ser Gin 135 ttt att gaa Phe Ile Giu 150 caa gag gac Gin Giu Asp aat cgc acg Asn Arg Thr ata qtg agg Ile Val Arg 200 Al a at c Ile cot Pro t cg Ser gag Giu acc Thr 105 cgt Arg gta ValI aca Thr aag Lys ggt Gi y 185 gaa Glu *ggt Gly *gca Aia cga *Arg cgc Arg gga Gly att Ile ttt Phe att Ile cog Pro ctg Le u 170 agg Arg gtc Val gct cga aaa gtc Al a gag Giu gga Gly gat Asp 75 cga Arg gcc Al a ct Pro gaa Giu cat His 155 att.
Ile atc Ile 9gC Arg ctt Leu tca Se r 60 ctg Leu act Thr gag Glu gc Ala gcc Al a 140 gtt ValI gtg Val a gt Ser tea Ser pLys gag Giu 45 cat His ott Leu gag Glu got Al a tgo Cys 125 gte Val1 cc Pro gtg Val Ott Leu ggt Gi y 205 gag Glu Val gea Ala cca Pro caa Gin cag Gin eta Leu 110 cgt Arg cag Gln gta Val1 att Ile Arg 190 ace Thr ceg Pro gga Gly, ga c Asp aca Th r tot Se r cg Pro 95 Ott Leu gte Val1 aaa Lys egg Arg tot Ser 175 gag Glu cga Arg at t Ile atg goc caa ect aat Met Ala Gln Pro Asn atg Met got Ala gta Vai
BO
ctg Leu e ca Pro ga c Asp ggg Gly ctt Leu 160 oct Pro ttg Leu ga a Giu caa Gin gca Ala 240 aaa Lys got Ala oaa Gin aaa Lys get Al a gte Val1 ca e His 145 oat His aat Asn tog Ser gca Al a gtg Val1 225 gee Ala gga Gly gaa Glu ttg Leu tgg Trp tot Ser 130 ttg Leu gct Ala oat His gaa Giu tta Le u 210 t ta Leu gaa Glu ott Leu ttt Phe cat His gt t Val 115 gtg Vai oaa Gin ogt Arg gag Gi u act Thr 195 caa Gin aac Asn ttg Leu gcg Al a act Thr gtt Val1 100 geg Ala atg Met ota Leu gt g Val1 tgg Trp 180 cog Pro ga a Glu agc Ser gco Ala ttg Leu ctt Leu gaa Glu ggg Gly ga c Asp aat Asn gg t Gly gtg Val 165 got Ala etg Leu tta Le u aa t As n ctt Leu 245 211 259 307 355 403 451 499 547 595 643 691 739 787 835 ctt gcg gat tat gao atg got Leu Ala Asp Tyr Asp Met Ala 215 220 got geg Ala Ala 230 gta cgt gtt Val Arg Val gt t ValI 235 gtt gaa gca ggg Val Glu Ala Gly ggt oct gca gta Gly Pro Ala Val WO 01/00804 ggt gaa tta gcc ttg cgt gat cat ctt gcg ctc ggc agg ctg ttg agt Gly Giu Leu Ala Leu Arg Asp His Leu Ala Leu Gly Arg Leu Leu Ser 250 255 260 gtg cca ttt gaa ggc agt gga gtt act cgt cct ctt aca gct gig tgg Vai Pro Phe Glu Gly Ser Gly Val Thr Axg Pro Leu Thr Ala Val Trp 265 270 275 agt gga ccc cgc aga ttg ccg att cta gcg gga gaa tta gtg icc atc Ser Gly Pro Arg Arg Leu Pro Ile Leu Ala Gly Giu Leu Val Ser Ile 280 285 290 gca icg aac cac aic igattttgag ccciggciaa cgg Ala Ser Asn His Ile 295 <210> <211> 298 <212> PRT <213> Corynebacterium gluiaxnicum PCT/IBOO/00922 883 931 979 1017 <400> Met Asp Asn Gly 1 Ile Al a Lys Ala Gin Lys Ala Val1 His 145 Giu Asn Leu Ala Thr Val 100 Alai Met Leu Trp 5 Gi y Ala Leu Leu Giu Gly Asp Asn Gi y Pro Asn Leu Gin Se r Ser ValI Val1 70 Trp Aia Met Ser Phe 150 Leu Gly Arg Ala Arg His Giu His Val Thr Ser Met Arg Thr 120 Ser Gin 135 Ile Giu Ala 25 Ile Pro Ser Glu Thr 105 Arg Val1 Thr Thr Gly Ala Arg Arg Gi y Ile Phe Ile Pro Leu Al a Gi u Gi y Asp Arg Al a Pro Giu H is 155 Ala Arg Le u Ser Leu Thr Glu Ala Ala 140 Val1 Phe ValI Ala Pro Gin Gin Leu 110 Arg Gin Val1 His Ala Arg Val Val Gin Giu Asp Lys Leu Ile Val Val Ile Ser Pro 175 WO 01/00804 PCTIBOOIOO922 Asn His Glu Trp Ala Asn Arg Thr Gly Arg Ile Ser Leu Arg Giu Leu 180 185 190 Ser Giu Thr Pro Leu Ile Val Arg Giu Val Gly Ser Gly Thr Arg Giu 195 200 205 Ala Leu Gin Giu Leu Leu Ala Asp Tyr Asp Met Ala Glu Pro Ile Gin 210 215 220 Val Leu Asn Ser Asn Ala Aia Vai Arg Val Val Val Giu Ala Gly Ala 225 230 235 240 Gly Pro Ala Val Leu Gly Giu Leu Ala Leu Arg Asp His Leu Ala Leu 245 250 255 Gly Arg Leu Leu Ser Val Pro Phe Giu Gly Ser Gly Val Thr Arg Pro 260 -265 270 Leu Thr Ala Val Trp Ser Gly Pro Arg Arg Leu Pro Ile Leu Ala Gly 275 280 285 *Giu Leu Val Ser Ile Ala Ser Asn His Ile 290 295 <210> 91 <211> 1214 <212> DNA <213> Corynebacteriui giutamicui <220> <221> CDS <222> (1191) <223> RXA02431 <400> 91 gtg gtg gtg aca ccc cgt cat atc gtt tac tcc gca. gcc tcg cgc cgg 48 Val Val Val Thr Pro Arg His Ile Val Tyr Ser Ala Ala Ser Arg Arg 1 5 10 gtg ttc caa atc gtg gaa aaa cgc gcc gga att gtc gaa cgc ctc agc 96 Val Phe Gin Ile Val Giu Lys Arg Ala Gly Ile Val Giu Arg Leu Ser 25 atc gat gaa ggc ttc atg gaa cca gag gct ctc gtt gga gcc acc cca 144 Ile Asp Glu Gly Phe Met Glu Pro Giu Ala Leu Val Giy Ala Thr Pro 40 gaa gag gtg aaa cag tgg gcg gaa qaa tta cgc gcg gaa att aaa gaa 192 Giu Glu Val Lys Gin Trp Ala Giu Giu Leu Arg Ala Giu Ile Lys Giu 55 gtt act ggc tta ccc tcc tcg gtt ggt gct ggc tee ggt aag cag ate 240 Val Thr Gly Leu Pro Ser Ser Vai Giy Ala Gly Ser Gly Lys Gin Ile 70 75 gcc aaa att ggt tca ggc gaa gea aag eca gat ggt gtg ttt gtc gtg 288 WO 01/00804 WO 0100804PCT/IBOO/00922 Ala Lys Ile Gly Ser Gly Glu Ala Lys Pro Asp Gly Val Phe Val Val cca Pro ct t Le u gt g ValI atc Ile 145 gga Giy t cc Ser gat Asp aaa Lys gao Asp 225 gat Asp gga Gi y gaa Glu atc Ile gta Val1 t gg Trp gaa Giu 130 agc Ser atc Ile caa Gin got Ala gac Asp 210 t tt Phe t ac Tyr ga a Giu gaa Giu gta ValI gac Asp gga Giy 115 aca Thr ctc Leu gac Asp gag Giu gcc Ala 195 gga Gly cgt Arg gca Ala gta Val tcc Ser 275 cca Pro aag Lys 100 gtg Val1 att Ile ggt Gly gac Asp cac His 180 atc Ilie cgc Arg at t Ile act Thr ggc Gly 260 cgc Arg cca Pro ca a Gir gg t Gly ggt Gly gca Al a cgc Arg 165 acc Th r att Ile ggt Gly gag Glu ctt Leu 245 ccc Pro caa Gin gca cat His ct *Pro gat Asp a cc Thr 150 ct Pro tat Tyr cga Arg gc Ala tct Ser 230 gag Glu etc Ile gao Asp ccc *gao IAsp gtg Val cta *Leu 135 atc Ile gtg Val1 geaa Giu toa Ser a ga Arg 215 cgt Arg gca Ala cgc Arg atc Ilie gao ttc Let a oa Thi 120 gca Ala gga Gi y ga a GI u aaa Lys gcc Ala 200 act Thr t cc Ser aca Thr ct t Leu ctc Leu 280 3oo ott Leu 105 ggc *Gly gog Ala ata Ile ccc *Pro gao Asp 185 gaa Glu gt c Val1 tao Tyr gca Ala gtc Val 265 ttc Phe gat Asp ga t Asp too Ser ota Leu toe Ser ogo Arg 170 ot 0 Leu ggc Gly ago Ser aco Thr ttc Phe 250 gga Gly cog Pro t at Tyr oca Pro aag Lys aco Tb r otg Leu 155 gc Ala oto Leu gca Ala gt g Val1 ttg Leu 235 cga Arg gta ValI gaa Glu gag Glu Ott Leu ott Leu Gin 140 t gg Trp gaa Glu acc Thr ceo His aaa Lys 220 too Ser ott Leu a gt Ser ott Leu gta Val 300 ct Pro gcc Al a 125 aaa Lys aac Asn gca Ala agg Arg cga Axg 205 otg Leu tat Tyr gc Ala ttt Phe gao Asp 285 ggc Gly gtq Val 110 toe Ser gaa Glu Ott Leu aaa Lys oaa Gin 190 cgg Arg cgg Arg gc Ala ogo Arg tot Ser 270 caa Gin gtg ValI ggC Gly atg Met gt a Val1 goo Ala ca g Gin 175 caa Gin oto Leu atg Met a cc Thr tao Tyr 255 ggt Giy caa Gin cae Gin gca Al a ggg Gly gaa Giu oge Arg 160 etc Ile gta Val oto Leu gc Ala ga t Asp 240 coo Pro ttg Leu etc Ile too Ser 336 384 432 480 528 576 624 672 720 768 816 864 912 Ala Pro Asp Thr 295 290 tot tot aqt too gaa Ser Ser Ser Ser Glu agt act cee gtt gae gcg cog cea get gto gog Ser Thr Gin Val Giu Ala Pro Gin Asp Val Ala WO 01/00804 WO 0100804PCT/IBOO/00922 305 310 ttg agt atg tgg tgc gca acg caa gat Leu Ser Met Trp Cys Ala Thr Gin Asp 325 cac ggt tgg gta caa ggt gcc ggt cac His Giy Trp Val Gin Giy Ala Gly His 340 345 gaa acc cgc agc ace aca aaa qgg cga Giu Thr Arg Ser Thr Thr Lys Gly Arg 355 360 gac ccg gac etc ace ccg gca gac cct Asp Pro Asp Leu Thr Pro Ala Asp Pro 370 375 gac tgg ttt gct gaa aat ggt gaa acg Asp Trp Phe Ala Glu Asn Gly Giu Thr 385 390 tcgggttteg ggg <210> 92 <211> 397 <212> PRT <213> Corynebacteriun giutamieun <400> 92 Val Val Val Thr Pro Arg His Ile Val 1 5 Val Phe Gin Ilie Val Glu Lys Arg Ala 25 Ile Asp Glu Gly Phe Met Glu Pro Glu 40 Glu Glu Val Lys Gin Trp, Ala Giu Glu 55 Val Thr Gly Leu Pro Ser Ser Val Gly 70 Ala Lys Ile Giy Ser Giy Glu Ala Lys Pro Val Asp Lys Gin His Asp Leu Leu 100 105 Leu Trp Giy Val Gly Pro Val Thr Giy 115 120 Val Glu Thr Ile Gly Asp Leu Aia Ala 130 135 gtc Val1 330 ggt Gi y act Th r eta Leu ggg Giy Tyr Gly Ala Leu Alia Pro ksp Ser 'eu 315 tac Tyr gt t Val aaa Lys gat Asp ga t Asp 395 Ser Ile Leu Arg Giy Asp Pro Lys Thr eac His gta Val agt Ser agt Ser 380 gac Asp Aila Val Vali Ala Ser Gly Leu Leu Gin 140 cca Pro t ca Se r ttt Phe 365 ttg Leu gaa Glu Al a Glu Gly Glu Gly Val1 Pro Al~a 125 Lys 320 gaa. tat ggc Glu Tyr Gly 335 gta cgt ttt Val Arg Phe 350 tcc atg gat Ser Met Asp gat tgg get Asp Trp Ala tagggtttca 1008 1056 1104 1152 1201 1214 Ser Arg Ala Ile Lys Phe Val1 110 Ser Glu WO 01/00804 Ile Ser Leu Gly PCT/IBOO/00922 Ala Thr Ile Gly Ile Ser Leu Trp Asn Leu Ala Arq 145 Giy Ser Asp Lys Asp 225 Asp Gly Giu Ile Ser 305 Leu His Giu Asp Ile Gin Al a Asp 210 Phe Tyr Glu Giu Val1 290 Ser Ser Gly rhr Pro Asp Giu Al a 195 Gly Arg Al a Val1 Se r 275 Pro Ser Met Trp Arg 355 Asp 150 *Asp His 180 Ile Arg Ile Thr Gi y 260 Arg Pro Ser Trp Val 340 Ser Leu I] Arg i165 Th z Ile Gly Giu Leu 245 Pro Gin Ala Gl u 325 Gin rhr [hr Pro Tyr Arg Ala Ser 230 Giu Ile Asp Pro Se r 310 Al a Giy Thr Pro Val1 Giu Se r Arg 215 Arg Ala Arg Ile Asp 295 Thr Thr Ala Lys kl a 375 Gi u Lys Ala 200 Thr Ser Thr Leu Leu 280 Thr Gin Gin Gly Gi y 360 Asp Pro Asp 185 Giu Val Tyr Al a Val1 265 Phe Asp Vali Asp His 345 Arg Pro Arg 170 ILeu Gly Se r Tb r Phe 250 Gly Pro Tyr Glu Val 330 Gly Thr Leu Al a Leu Ala Val Leu 235 Arg Vai Giu Glu Al a 315 Tyr Val1 Lys ksp IGiu Thr His Lys 220 Ser Le u Se r Leu Val1 300 Pro His Val1 Ser Ser 380 Ala Arg Arg 205 Leu Tyr Ala Phe Asp 285 Gly Gin Pro Se r Phe 365 Leu Lys Gin 190 Arg Arg Al a Arg Ser 270 Gin Val1 Asp Giu Val 350 Ser Asp Gin 175 Gin Leu Met Thr Tyr 255 Gly Gin Gin Val Tyr 335 Arg Met Trp 160 Ile Val Leu Ala Asp 240 Pro Leu Ile Ser Al a 320 Gly Phe Asp Al a 370 Asp Trp Phe Aia Glu Asn Gly Giu Thr Giy 385 390 <210> 93 <211> 558 <212> DNA <213> Corynebacteriui giutamicum <220> <221> CDS Asp Asp Giu 395 WO 01/00804 PCT/IBOO/00922 <222> (535) <223> RXA02446 <400> 93 caggaaatct tgctgtctaa tgcacaacgg aaaactgctc acggacgaac tagttgtaqc gagcgtattc tttgtgttct ctcacgacag gaatactgct atg gcg atc gag tcc 115 Met Ala Ile Glu Ser 1 atc gcg tac acc agt g~a gca ctc tca acc ggc agt ggc cgg ctg ggg 163 Ile Ala Tyr Thr Ser Glu Ala Leu Ser Thr Gly Ser Gly Arg Leu Gly 15 cat gtg cgc tcc aca gat ggt gcg ctc gaa ttt gaa atg aca ccg cca 211 His Val Arg Ser Thr Asp Gly Ala Leu Glu Phe Glu Met Thr Pro Pro 30 aag gct ttg qgc gga tcc gqt gaa ggc acc aat cca gaa cag ctg tic 259 Lys Ala Leu Gly Gly Ser Giy Glu Gly Thr Asn Pro Glu Gin Leu Phe 45 gcg gta ggt tac gca gcc tgt ttc cac tct gcc atg cac tct gtc gca 307 Ala Vai Gly Tyr Ala Ala Cys Phe His Ser Ala Met His Ser Val Ala 60 cgc agc cgc aag atc act cit gaa gac aca gcg gtt ggt gcc cga gtt 355 Arg Ser Arg Lys Ile Thr Leu Giu Asp Thr Ala Val Gly Ala Arg Val 75 80 agc atc ggg cca aac ggc gct ggt gga ttt gag att gcc gta gaa ctc 403 Ser Ile Gly Pro Asn Gly Ala Gly Gly Phe Glu Ile Ala Val Glu 1.eu 95 100 gaa gta tcg ait cct caa ttg cca caa gca gaa gcc cag gaa cit gct 451 Glu Val Ser Ile Pro Gin Leu Pro Gin Ala Giu Ala Gin Giu Leu Ala 105 110 115 gat gcc gcg cac cag gig tgc ccg tat tcc aac gcc aca cga ggc aat 499 Asp Ala Ala His Gin Val Cys Pro Tyr Ser Asn Ala Thr Azg Gly Asn 120 125 130 atc tcg gta act gig tca gtc atc gac gaa gag gct taaaaccaca 545 Ile Ser Val Thr Val Ser Val Ile Asp Giu Glu Ala 135 140 145 ggattaacaa aac 558 <210> 94 <211> 145 <212> PRT <213> Corynebacterium glutamicun <400> 94 Met Ala Ile Glu Ser Ile Ala Tyr Thr Ser Glu Ala Leu Ser Thr Gly 1 5 10 WO 01/00804 Ser Gly Arg Leu Gly His Vai Arg Ser Thr Asp Giu Met Thr Pro Pro Lys Ala Leu Gly Gly Ser Pro Giu Gin Leu Phe Ala Val Gly Tyr Ala Ala 55 Met His Ser Val Ala Arg Ser Arg Lys Ile Thr 70 75 Val Gly Ala Arg Val Ser Ile Giy Pro Asn Giy Ile Ala Val Glu Leu Giu Val Ser Ile Pro Gin 100 105 Ala Gin Glu Leu Ala Asp Ala Ala His Gin Val 115 120 Ala Thr Arg Gly Asn Ile Ser Val Thr Val Ser 130 135 Al a 145 <210> <211> 1206 <212> DNA <213> Corynebacteriwn qiutamicun <220> <221> CDS <222> (1183) <223> RXA02861 <400> ccctcgatta ttacaatccg gctacttcgg aagcgtttgt gaaggtatta atacttcttt aagggtcqga ggattttcgt PCT/IBOO/00922 Gly Giy Cys Leu Ala Leu Cys Val1 140 Phe Asn Al a Ala Glu Glu Asn Glu ggccggattt ttctatcctg atg ict act aga aca Met Ser Thr Arg Thr 1 acg cca caa gac cgt tat acc gac gaa tac ggc atc gaa cgc gtc aac Thr Pro Gin Asp Arg Tyr Thr Asp Glu Tyr Gly Ile Glu Arg Val Asn 15 aag gat gaa ccc qgc ctg gtg gac aaa ctc cgg gac aag cac gac tgg Lys Asp Giu Pro Gly Leu Val Asp Lys Leu Arg Asp Lys His Asp Trp 30 ttt gat cat ctc atg cgc atg aat gaa cgt ttc ggc gca aaa ggt ggc Phe Asp His Leu Met Arq Met Asn Giu Arg Phe Gly Ala Lys Gly Gly 45 115 163 211 259 WO 01/00804 aac caa ttg tcg gcg gqt att acg tat ttc tcc gtg ctg tcg Asn Gin Leu Ser Ala Gly Ile Thr Tyr Phe Ser Val Leu Ser PCT/IBOO/00922 atc ttc 307 Ile Phe ccg Pro aac Asn gaa Glu gcg Ala tct Ser tgg Trp 150 gac Asp ggt Gi y ttt Phe gtc Val ct g Le u 230 cag Gin gga Gly att Ile cct Pro ggc Giy cag Gin gga Gi y 135 gcc Ala t tg Leu atc Ile gtg Vai gca Al a 215 att Ile gca Ala gCC Ala gaa Giu gag Glu cg t Arg 120 ctg Leu att Ile gtc Val1 a cg Thr ggc Gly 200 gca Ala ttc Phe gca Ala atg Met gt t Vali atc Ile 105 ggt Gly g gg Gly gac Asp gcg Ala gcg Ala 185 ctg Leu ctt Leu tc Se r ctg Leu ctt Le.
ct c Leu ggt G1y gct Ala tgg Trp cc a Pro ct g Leu 170 ctc Leu ggg Gi y gt t Val1 ctg Leu ctt Leu 250 gtc aVal 75 aca aThr aac Asn gtg Val1 atg Met act Thr 155 atc Ile ggt Gly gag Glu ggt Gly cca Pro 235 9qc Gly ttc Phe gat Asp acc Th r t tg Leu 9 cg Ala 140 gaa Giu gtc Vali gct Ala att Ile gtc VJal 220 cgt bArg gca kla ggt Gly att Ile gtc Val1 Gi y 125 aac Asn ggc Gi y ttg Leu tcc Ser ccg Pro 205 t tg Leu acc Thr atc Ile *att Ile *caa *Gin aac Asn 110 at t Ilie ctg Leu aac Asn ctg Leu gga Gly 190 99C Gly gct Al a aaa Lys ggt Gly gca Ala aat As n 95 ggc Gi y gg t Gi y cgc Arg ttc Phe ctg Leu 175 cta Leu att Ile aac Asn gt t Val I:ttt Phe 255 ggt Gly 80 cga Arg atc Ile gg t Giy ttt Phe att Ile 160 gcc Ala acc Thr agc Ser ttc Phe ccc Pro 240 gag Glu gt c Val1 atc Ile att Ile gta Val1 gga Giy 145 ca a Gin atg Met aaa Lys tac Tyr ctg Leu 225 at g Met gtg Val1 atc Ile aac Asn gat Asp act Th r 130 gt t Val1 aag Lys ggC Gly aac Asn atc Ile 210 gtg Val1 aaa Lys gtc Val ct t Leu ga t Asp t cc Se r 115 gcc Ala tcc Ser a ag Lys gta Val1 ct g Leu 195 acc Th r ttc Phe ccg Pro a ag Lys gcc Ala gct Ala 100 gcg Ala ctg Leu cgc Arg ctc Leu gcc Ala 180 ct g Leu tgg Trp atg Met ggt Gly cag Gin 260 gga Giy tta Leu att Ile t gg T rp a tg Met acc Th r 165 tt c Phe gac Asp gtg Val1 t gg Trp ctt Leu 245 gtt ValI 355 403 451 499 547 595 643 691 739 787 835 883 931 tcg ctg ttg gct tca aat gca ttg agt aac ccc gcg ggt gca gca Ser Leu Leu Ala Ser Asn Ala Leu Ser Asn Pro Ala Gly Ala Ala ttc Phe atc Ile cg t Arg 310 cat His ggC Gly t tg Leu WO 01/00804 ggt ccg atc atc ggc ate atg gtt qtg ctg Gly Pro Ile Ile Gly Ile Met Val Val Leu 280 285 ctc atg tat tgc tct gcg tgg get gcc acc Leu Met Tyr Cys Ser Ala Trp Ala Ala Thr 295 300 ctt gcg act gtt cca gca cca gag ect gcg Leu Ala Thr Val Pro Ala Pro Glu Pro Ala 315 320 gaa att gat eca ggt gaa qaa gtc tcc caa Gin Ilie Asp Pro Gly Giu Gin Val Ser Gin 330 335 att gga gtg gee gtg ggt gcc gcg act gcg Ilie Gly Val Ala Val Gly Ala Ala Thr Ala 345 350 cgt aaa aaa tagtttttat taagggcatt ccc Arg Lys Lys 360 PCT/IBOO/00922 979 1027 1075 1123 1171 1206 <210> 96 <211> 361 <212> PRT <213> Corynebacterium giutamicum <400> 96 Met Ser Thr Arg Thr Thr Pro Gin 1 5 Ile Gin Arg Val Asn Lys Asp Gin Asp Lys His Asp Trp Phe Asp His 40 Gly Ala Lys Gly Gly Asn Gin Len S 55 Val Len Ser Ilie Phe Pro Ile Ala M 70 Vai Ile Len Ala Gly Asn Pro Gin V Ile Asn Asp Ala Leu Giu Gly Gin I 100 1 Ilie Asp Ser Ala Ilie Ala Gin Arg G 115 120 Val Thr Ala Leu Trp Ser Gly Leu G 130 135 Nsp Arg Tyr Thr Asp 10 Pro Gly Len Val Asp 25 ,eu Met Arg Met Asn ,er Ala Gly Ile Thr let Len Val Phe Gly ~al Len Thr Asp Ile 90 le Gly Asn Thr Val 05 ly Ala Vai Leu Giy 125 ly Trp Met Ala Asn 140 Gin Lys Gin Tyr Ile Gin As n 110 Ile Len Tyr Len Arg Phe Ala As n Gly Gly Arg Gly 145 Gin Met Lys Tyr Leu 225 Met Val1 Pro Tyr Ser 305 Ile Ser Gi y WO 01/00804 Val Ser Arg Lys Lys Leu Gly Val Ala 180 Asn Leu Leu 195 Ile Thr Trp 210 Val Phe Met Lys Pro Gly Val Lys Gin 260 Ala Gly Ala 275 Leu Ile Trp 290 Glu Glu Ala Ile Arq Val Ala Arg Lys 340 Ala Phe Ala I 355 Met Trp 150 Thr Asp 165 Phe Gly Asp Phe Val Val Trp Leu 230 Leu Gin 245 Val Gly Akla Phe 'Arg Ilie Leu Arg 310 ),rg His 325 fai Gly ~eu Leu PCTIBOO/00922 Ala Ilie Asp Pro Thr Giu Gly Asn Phe Ile Leu Ile Val Ala 215 Ile Al a Ser Gi y Leu 295 Leu Glu Ile Arg Val1 Thr Gi y 200 Al a Phe Ala Leu Pro 280 Met Ala Ile Gly Lys 360 Al a Al a 185 Leu Leu Ser Leu Leu 265 Ile Tyr Thr Asp Val 345 Lys Leu 170 Leu Gly Val1 Leu Leu 250 Al a Ile Cys Val Pro 330 Ala Ile Gly Glu Gly Pro 235 Gly Ser Gly Ser Pro 315 Gly Val ValI Ala Ile Val1 220 Arg Al a Asn Ile Ala 300 Ala Glu Gly Leu Leu Ser Gly 190 Pro Giy 205 Leu Ala Thr Lys Ile Gly Ala Leu 270 Met Val 285 Trp Ala Pro Giu Glu Val Ala Ala 350 <210> 97 <211> 753 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <223> RXA00981 <400> 97 aaccaatggc tgggtactga tgtggtgatc agtgcccagt ttcttctttc tactagtgtc WO 01/00804 ggatagaagt acccccagtc cagaatgaag gtcaccacca PCTIIBOO/00922 atg tca gag aat ttq 115 Met Ser Giu Asn Leu cca Pro aac Asn att Ile ca g Gin aca Th r t cc Ser atc Ile acc Thr aac As n cct Pro 150 atc Ile tac 9g Ala ttc Ph e ga t Asp ct g Leu cca Pro ctc Leu gt c Val aac As n cca Pro 135 gtc Vali Cqc Arg tac Iccc gag Pro Glu cgc aac Arg Asn gag atc Giu Ile cac gaa His Giu gaa agc Giu Ser gca gct Aia Aia tgc agt Cys Ser 105 caa aaa Gin Lys 120 aag ccg Lys Pro tto otg Phe Leu acc attC Thr Ile I aaa ttt g aat As r gaa ci u ct g Leu tao Tyr atc Ile atc Ile ttc Phe gao Asp aac sAsn :ct 3er Jcc lia raa *ct' SLet tta ILeu a cc Thr gca Aia gt c Vali 75 aaa Lys ct C Leu gtc Val ggo Gly aac Asn 155 atg Met caa -ctg gac Leu Asp acg ggg Thr Gly aag atc Lys Ile 45 cot ato Pro Ile 60 aaa aag Lys Lys gac aca Asp Thr aaa gat Lys Asp acg gtc Thr Val 125 tao aag Tyr Lys 140 too gtg Ser Vai gao ttc Asp Phe gaa gtt gc Ala ttc Phe 30 aac As n gag Giu gt 0 Vali gtg Val gcc Ala 110 ato Ile agt Ser gaa Giu t gg 1'rp C.ot gag Giu 15 atg Met atc Ile cac His ato Ile ttt Phe 95 tac Tyr gag Giu ttg Leu aag Lys gca Ala 175 cag t aga A-rg ctc Leu ctg Leu gta Vali cga Arg 80 ga t Asp gca Ala gcc Alia cao His gto lai 160 ~gc er :ca att Ile aac Asn aaa Lys tot Ser aaa Lys atc Ile atc Ile aaa Lys ott Leu 145 sat A.sn ct o .Leu Ito ca~ GlT tac Tyz act Thr t ca Ser gga Giy gca Al a gco Al a gao Asp 130 atc Ile gtt Val gag Giu ott Leu I atg atc Met Ile caa ttt Gin Phe gaa ttc Giu Phe c ga ttg Arg Leu gao gag Asp Giu ggc att Gly Ile 100 gat atg Asp Met 115 tao ato Tyr Ile oto caa Leu Gin gaa gto Giu Val cac aaa His Lys 180 gat gag Asp Giu 195 aag Lys ggC Gly agc Se r aa g Lys ctc Leu cga Arg ctg Leu got Ala gt g ValI ca g Gin 165 ato Ile cto Leu 163 211 259 307 355 403 451 499 547 595 643 691 Tyr Tyr Lys Phe Giu Gin Giu Val Pro Gin Ser Ilie 185 190 agt gaa gat gga Ser Giu Asp Gly 200 gttgaaaoca ctg aag aat cca cgg Lys Asn Pro Arg gga agt gaa gtc Gly Ser Giu Val act taaacctcca Thr 210 WO 01/00804 WO 0100804PCTIBOO/00922 <210> 9B <211> 210 <212> PRT <213> Corynebacterium giutamicun <400> 98 Met Ser Giu Asn Leu Pro Ala Pro Glu Asn Leu Leu Asp Ala Giu Arg 1 Ile Asn Lys Ser Lys Ile Ile Lys Leu 145 Asn Leu Gin T yr Thr Ser Gly Al a Al a Asp 130 Ile Val Glu 5 Ile Lys Phe Gly Phe Ser Leu Lys Glu Leu Ile Arg 100 Met Leu Ile Ala Gin Val Val Gin 165 Lys Ilie 160 Asn Ile Gin Thr 70 Ser Ii. e Thr Asn Pro 150 Ile Tyr Phe Asp Leu Pro Leu Val Asn Pro 135 Val1 Arg Tyr Arg Glu His Glu Al a Cys Gin 120 Lys Phe Thr Lys Asn 25 Ile Glu Ser Al a Se r 105 Lys Pro Leu Ile Phe 10 Glu Leu Leu Thr Tyr Ala Ilie Val 75 Ile Lys 90 Phe Leu Asp Val Asn Gly Ser Asn 155 Ala Met 170 Giu Gin Gly Ile Ile Lys Thr Asp Val 125 Lys Val Phe Val Phe Met Asn Ile Giu His Val Ile Val Phe Ala Tyr 110 Ile Giu Ser Leu Glu Lys Trp Ala 175 Pro Gin 190 Leu Leu Val1 Arg Asp Al a Al a His Val1 160 Se r Ser 185 Ile Leu Asp Giu Leu Ser Giu Asp Gly Lys Asn Pro 195 200 Val Thr 210 <210> 99 <211> 1098 <212> DNA <213> Corynebacterium glutamicum <220> Gly Ser Giu WO 01/00804 <221> CDS <222> (1075) <223> RXN00786 <400> 99 tccttcttcc accagctaaa agtgaattac eccgcctttg PCTIBOOIOO922 teqgggtggt tgcattecca gtctaggtgt ttagcetcaa cgttggatac getgggaggc atg age tca ect gtt Met Ser Ser Pro Val atc Ile cgc Arg geg Ala cac His gte Val1 gca Al a at c Ile gaa Glu cac His aaa Lys 150 ttc Phe ec Pro tac Tyr gag Glu cgt Arg gaa Glu ggc Gi y get Al a cag Gin 120 gge Gi y cac His aac Asn gaa ace Glu Thr tgt gee Cys Ala gaa tac Glu Tyr tac gt Tyr Val gca tct Ala Ser gig age Val Ser att gac Ile Asp 105 cge ttt Arg Phe eat gaa His Glu etq gtt Leu Val gat gaa Asp Glu 170 a aa Lys ggC Gly ggc GI y gig ValI gaa Giu 75 eca Pro 9g Ala gat Asp ga a Glu gac Asp 155 cca Pro ace Th r gt a Val1 gee Ala gac Asp gca Ala atg Met gee Ala aag Lys gta ValI 140 qge Gly aae Asn gga Gly gac Asp cca Pro 45 ace Thr eca Pro gte Val1 tge Cys eag Gin 125 gag Glu gitt Val1 Ct g Leu aag aag Lys Lys egt gea Arg Ala att tat Ile *Tyr ctg gea Leu Ala gaa ggt Giu Gly eac gaa His Glu ceg ctg Pro Leu 110 gga tte Gly Phe gge acc Gly Thr get gge Ala Gly ate tgg Ile Trp 175 ate Ile gtg Val1 gte ValI gaa Glu gee Al a ga a GI u gte Val1 ca c His atg Met at Ile 160 ctg Leu ctt Leu ace Thr aaa Lys ggc Gly atg Met gca Ala aaa Lys etc Leu 130 cat His ace Thr cag Gin tet gtg gac gag Ser Val Asp Giu ace atg gag ate gte ege gag ctg aag Thr Met Glu Ile Val Arg Giu Leu Lys gtg aag tte Val Lys Phe ect c.
Pro G.
aac ci Asn A.
2.
att gi Ile V~ 230 gtc gc Val A cgc g~ Arg GI tec t( Ser SE cgc ct Arg L 2S WO 01/00804 185 ag ctg cag ln Leu Gin 200 gc cag gtt rg Gin Val 15 tg gte ggt al Vai Gly ct aag caa La Lys Gin ia atc gac Lu Ile Asp 265 :c ggc get 3r Gly Ala 280 :g gct gag !u Ala Glu 55 gat Asp gee Ala tee Ser aac Asn 250 cca Pro tcc Ser ttc Phe cca Pro gtC Va1 cgc Arg 235 ggt Gly gca Ala gtg Val ggc Gi y ccg Pro aag Lys 220 aac Asn gee Ala tgg Trp cct Pro tac Tyr 300 tea Ser 205 gct Ala tee Ser gat Asp ttc Phe gag Glu 285 gac Asp 190 gat Asp atc Ile tec Ser aac Asn gaa Glu 270 ate Ile gac Asp tge Cys cgc Arg 225 gtt Val ctg Leu gag Glu cag Gin gaa Glu 305 PCTIBOO/00922 acg Thr etg Leu gtt Vai tac Tyr 260 ggt Gly ati Ile tCe Ser 739 787 835 8B3 931 979 1027 1075 1098 gct gag aag att Ala Giu Lys Ile 310 gtt Val ttc gcg ctg cct cge gtg ctg cgc cac aag aat Phe Ala Leu Pro Arg Vai Leu Arg His Lys Asn 315 taattgeaag aatgaaaaat ccc <210> 100 <211> 325 <212> PRT <213> Corynebacterium giutanicum <400> 100 Met Ser Ser Pro Val Ile Ser Pro Glu Thr Lys Thr Gly Lys Lys Ile 1 5 10 Leu Leu Ala Ala Pro Arg Gly Tyr Cys Aia Gly Vai Asp Arg Ala Vai 25 Glu Thr Val Giu Arg Ala Leu Giu Glu Tyr Gly Ala Pro Ile Tyr Vai 40 Arg Lys Giu Ile Val His Asn Arg Tyr Vai Val Asp Thr Leu Ala Glu 55 Lys Gly Ala Ile Phe Val Asn Giu Ala Ser Giu Ala Pro Glu Gly Ala 70 75 WO 01/00804 PCT/IBOO/00922 Asn Met Val Phe Ser Ala His Giy Val Ser Pro Met Val His Glu Glu 90 Ala Ala Ala Lys Asn Ile Lys Ala Ile Asp Ala Ala Cys Pro Leu Val 100 105 110 Thr Lys Val His Lys Giu Val Gin Arg Phe Asp Lys Gin Gly Phe His 115 120 125 Ilie Leu Phe Ile Gly His Glu Gly His Giu Glu Val Giu Gly Thr Met 130 135 140 Gly His Ser Val Giu Lys Thr His Leu Val Asp Gly Val Ala Gly Ile 145 150 155 160 Ala Thr Leu Pro Glu Phe Leu Asn Asp Giu Pro Asn Leu Ile Trp Leu 165 170 175 Ser Gin Thr Thr Leu Ser Val Asp Giu Thr Met Giu Ile Val Arg Glu 180 185 190 Leu Lys Val Lys Phe Pro Gin Leu Gin Asp Pro Pro Ser Asp Asp Ile 195 200 205 Cys Tyr Ala Thr Gin Asn Arg Gin Val Ala Val Lys Ala Ile Ala Giu 210 215 220 Arg Cys Giu Leu Met Ilie Val Val Gly Ser Arg Asn Ser Ser Asn Ser 225 230 235 240 Val Arg Leu Val Giu Val Ala Lys Gin Asn Gly Ala Asp Asn Ala Tyr 245 250 255 Leu Val Asp Tyr Ala Arg Giu Ile Asp Pro Ala Trp Phe Glu Gly Val 260 265 270 Giu Thr Ilie Gly Ilie Ser Ser Gly Ala Ser Val Pro Giu Ile Leu Val 275 280 285 Gin Gly Val Ile Glu Arg Leu Ala Glu Phe Gly Tyr Asp Asp Vai Giu 290 295 300 Glu Val Thr Ser Ala Ala Glu Lys Ile Val Phe Ala Leu Pro Arg Val 305 310 315 320 Leu Arg His Lys Asn 325 <210> 101 <211> 1131 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS WO 01/00804 <222> (101)..-(1108) <223> RXS01027 <400> 101 aatagatgqa agtagttttt cattcactta. tgtgcgcgtt PCT/IBOO/00922 tttaatctgg tttctaccaa gaactgtgtg caccacaacg cggaaggtga atcgcaccca atg qca aat aag aac Met Ala Asn Lys Asn aat Asn aac Asn cgc Arg aac Asn ga c Asp aca Thr ctg Leu aaa Lys ccc Pro t gc Cys 150 gca Ala a ag Lys ggt Gi y cca Pro ccg Pro tgg Trp acc Thr ggc Gly qtg Val1 aac As n 135 gag Glu aag Lys cct Pro cgc Arg act Thr gac Asp t cc Ser gcg Al a aag Lys gt c Val1 120 gat Asp ttg Leu cgt Arg cat Hisa ctg' Leu ctt Leu agc Ser ct g Leu gcc Ala ctg Leu 105 tac Tyr gaa.
Glu ctc Leu ttc Phe *gag *Glu caa Gin gca *Ala atc Ile gcc Ala cgt Arg atc Ile tac Tyr gtt Val agc Ser cgc Arg 170 gtg ValI cag Gin gca Al a gag Giu aag Lys 75 ga Giu ggc Gi y t gg Trp ga t Asp t ac Tyr 155 act rhr gac Asp atc Ile ggt Gly gtc Val 60 9gc Gly atc Ile aag Lys act Thr ga Giu 140 caa Gin cct Pro aaa Lys ccg Pro gca Al a 45 gct Ala ass.
Lys Ct t Leu gtt Val1 gcc Ala 125 atc Ie gta.
Val1 tcc Se r gac Asp gcg Ala 30 gta Val gt c Val gt c ValI ga Glu act Thr 110 cag Gin cgt Arg gat Asp acc Thr caa Gin 15 cgt Arg ct g Leu stc Ile gat Asp ga Glu 95 tac Tyr gt t Val1 tgg Trp acc Thr act rhr 175 gat Asp ccc Pro tgg Trp cac His ccc Pro 80 act Thr cct Pro ctt Leu ct g Leu ga a Giu 160 c9g Arg 1 tca Ser act Thr cgc Arg cgc Arg gqc Gi y Gly gtg Vai ggt Gly t ct Ser 145 gt t Vali gt g Val1 gcc Ala gag Giu Gly ccg Pro gag Gi u tac Tyr ctc Leu gga Gly 130 gtt Val1 ct g Leu ctg Leu at g Met ga Giu gac Asp cac His tct Ser gac Asp ga c Asp 115 gag Gi u ga t Asp gcc Al a tat Tyr ctg Leu 20 ttc Phe atc Ile tat Tyr att Ile atc Ile 100 cga.
Arg ttt Phe gas Glu aag Lys gtt Val1 180 atc Ile acc Thr scc Thr ga t Asp ccg Pro cgt Arg acc Thr gt c Val gca Ala gca Ala 165 cgC Arg 115 163 211 259 307 355 403 451 499 547 595 643 cat gct cat ga cat His Ala His Ala His 185 cgc caa acc tgg Arg Gln Thr Trp 190 ggt ggc gac Gly Gly Asp gac aat aag Asp Asn Lys 195 WO 01/00804 WO 0100804PCT/IBOO/00922 ggg Gly ccc Pro 220 ctc Leu ttc Phe ttc Phe ggC Gly ctc Leu 300 t tg Leu cgt Arg 205 acc Thr ccc Pro ggC Gly acc Thr gac Asp 285 cct Pro a gc Sex ccc Pro ga t Asp gac Asp 245 ccc Pro gt g ValI tgg T rp aaa Lys ggC Gly 739 787 835 883 931 979 1027 1075 Gly Val Phe Thr gct gat tac ctg Ala Asp Tyr Leu agt tcc ctg ccg gtt aaa taggagcgcg tttaaggcct 1128 Ser Ser Leu Pro Val Lys cca <210> 102 <211> 336 <212> PRT <213> Corynebacterium giutamicum~ <400> 102 Met Ala Asn Lys Asn Asn Lys Pro His Giu Val Asp Lys Asp Gin Asp 1 5 10 Ser Ala Met Leu lie Asn Gly Arg Leu Gin Gin Ile Pro Ala Arg Pro 25 Thr Glu Glu Phe Thr Arg Pro Thr Leu Ala Ala Gly Ala Val Leu Trp 40 Arg Gly Asp Ilie Thr Asn Pro Asp Ser Ile Glu Val Ala Val Ile His 55 1131 wo 01/00804 WO 0100804PCTIIBOO/00922 Arq Pro His Tyr Asp Asp Trp, Ser Leu Ala Lys Gly Lys Val Asp Pro Gly Gly Val1 Gl y Ser 145 Val ValI Gly Glu Ser 225 Glu Trp Ala Glu Lys 305 75 Glu Tyr Leu Gly 130 ValI Leu Leu Asp Met 210 Al a Leu Glu Gln Met 290 Ser Asp Asp Glu Asp Al a Tyr Asp 195 Leu Val Gly Thr Gly 275 Ile I le Ile 100 Arg Phe Glu Lys Val 180 Asn Val1 Pro Leu Asp 260 Gi y Lys Pro *Arg Th r Val1 Al a Al a 165 Arg Lys Pro Asp Asp 245 Pro Val Trp Thr Leu Lys Pro Cys 150 Al a His Arg Met Arg 230 ValI Glu Pro Phe Lys 310 *Thr Gly Val Asn 135 Glu Lys Al a Pro Leu 215 Cys Ser Al a Met Ser 295 Gly Ala Lys Val1 120 Asp Leu Arg His Leu 200 Leu Gln Val1 Cys Ile 280 Glu Ser Ala Leu 105 Tyr Glu Leu Phe Ala 185 Asp Pro Ala Asn Lys 265 ValI Asn Val *Arg 90 Ile Tyr Val S er Arg 170 His Lys Phe Thr Arg 250 Lys Gly Gly Trp Glu Gly Trp Asp Tyr 155 Thr Gl y Lys Lys Ala 235 Leu Arg Gln Thr Val 315 Ile Lys Th r Glu 140 Gln Pro Arg Gly Pro 220 Leu Phe Phe Gl y Leu 300 Leu Leu Val1 Al a 125 I le Val Ser G In Arg 205 Th r Pro Gly Thr Asp 285 Pro Se r Glu Thr 110 Gin Arg Asp Thr Thr 190 Arg Ala Leu Asp Asp 270 Ile Ile Phe Glu Thr Tyr Pro Val Leu Trp Leu Thr Glu 160 Thr Arg 175 Trp Gly Gln Ala Ile Tyr Ala Asp 240 Asp Ala 255 Val Val Ile Pro Asp Glu His Asp 320 Ile Lys Ala Lys Gly Val Phe Thr Ala Asp Tyr Leu Ser Ser Leu Pro Val Lys 335 <210> 103 WO 01/00804 <211> 651 <212> DNA <213> Coryriebacterium giutamicum <220> <221> CDS <222> (101)..(628) <223> RXS01528 <400> 103 cacccaaacc caaacctctc agtcgaataa gcagaagtct PCT/IBOO/00922 caggacaacc gcaggggtaa gggtcgtagg tctccaacca ggaggcgttc caacacgagg gtg aat cag gcg tgg Val Asn Gin Ala Trp cag Gin gtg Val1 ctg Leu cgt Arg aag Lys ggt Gi y gaa Glu gt t Val t gg Trp cgg Arg 150 cag Gin gt g Val1 tcg Se r ttg Leu gc t Al a gag Glu ggg Gly gat Asp att Ile 135 aa g Lys tce Ser t ca Ser aag Lys t tg Leu gcg Ala gtg Val1 aag Lys ggc Gi y 120 ccg Pro ttg Leu cgt Arg ggt Gi y att Ile t gg T rp act Thr ttc Phe Cgg Arg 105 ga t Asp gcg Ala gct Ala t tg Leu ttg Leu tat Tyr tcg Ser get Al a act Th r ate Ile ttg Leu aat Asn agg Arg gtt Val1 gct Ala gt t Val1 atg Met gag Glu 75 gag Glu cat Hi s aat As n ca g Gin cag Gin act Thr gag Glu gcg Ala ccg Pro 60 cgt Arg ttg Leu aag Lys ga t Asp ttg Leu 140 gcg Ala t ct Ser gcg Ala ttg Leu 45 aag Lys gag Glu ggt Gly acq Thr gag Glu 125 att Ile cat His gat Asp gtc Val1 30 att Ile Gi y gtg Val1 gtg ValI gtg Val 110 gat Asp gag Glu ga t Asp gag Glu 15 aac Asn ggt Gly cat His tgg Trp att Ile 95 cat His cca Pro cat His ttg Leo act Tb r gct Al a cgc Arg gtt ValI gag Glu 80 gat Asp cat His gaa Glu ttg Leo ttg Leu 1 tcc gca Ser Ala aac aat Asn Asn ctt gat Leo Asp gag cct Glu Pro gag acc Glu Thr tat tgg Tyr Trp cat ttg His Leu gtc act Val Thr 130 gct ttt Ala Phe 145 cct gag Pro Glu ggt ggt ctc Gly Gly Leu gag gtt gat Glu Val Asp cgt cgt ggt Arg Arg Gly ggt gag gat Gly Glu Asp ggc atc cac Gly Ile His ttc gtt tcg Phe Val Ser 100 ttg cgt tat Leo Arg Tyr 115 gag gtg gcg Glu Val Ala gcg gat gag Ala Asp Glu ttt gct ttg Phe Ala Leo 163 211 259 307 355 403 451 499 547 595 155 aag gaa aag gcg gag gga agg tcc acc cca agg tgattccgaa ccccaacccg 648 WO 01/00804 Lys Glu Lys Ala Glu Gly Arg Ser Thr Pro Arg 170 175 aac <210> 104 <211> 176 <212> PRT <213> Corynebacteriun glutamicum PCT/IBOO/00922 651 <400> 104 Val Asn Gln Ala 1 Ser Asn Leu Glu Glu Tyr His Val1 Al a 145 Pro Ala Asn Asp Pro Thr Trp Leu Th r 130 Pbe Glu GI y Val1 Arg Glu Ile Val 100 Arg Val Asp Al a Trp 5 Leu Asp Gly Asp His Ser Tyr Ala Glu Leu 165 Gin Gin Ser Arg Val Val Ser Gly 25 Leu Ser Lys Ile Arg Leu Leu Trp Lys Ala Ala Thr Gly Glu Val Phe- Glu Gly Lys Arg 105 Val Asp Gly Asp 120 Trp Ile Pro Ala 135 Arg Lys Leu Ala 150 Lvs Glu Lvs Ala Leu Leu Tyr Ser Ala Thr Ile Leu Asn Arg Glu 170 Asp Val Ile Gly ValI Val1 Val1 110 Asp Glu Asp Thr <210> 105 <211> 509 <212> DNA <213> Corynebacterium glutamicum <22 0> <221> CDS <222> (486) WO 01/00804 WO 0100804PCT/IBOO/00922 <223> RXS01716 <400> 105 gaa gtc act Chi Val Thr 1 gtt cgc ctg Val Arg Leu gca atc gag Ala Ile Glu gaa acc cat Glu Thr His cgc gat gcg Arg Asp Ala ctg tcc aag Leu Ser Lys gag gaa gct Glu Glu Ala gac caa ggt Asp Gin Gly 115 ttc atc gtt Phe Ile Val 130 caa atg gga Gin Met Gly 145 cct Pro ggc Gly cgc Arg ggg Gi y tcc Ser atc Ile ctg Leu 100 cct Pro ggc Gly tgc Cys gag Giu 5 aaa Lys act Th r gta Val aac Asn cgt Arg ctg Leu ttc Phe acc Thr gtg Val gga Gly ggc Gly cgt Arg gag Glu cgc Arg 70 cct Pro tcc Se r tgt Cys tac Tyr cgc ttc Phe gtc ValI gtc Val gcc Al a ga t Asp gga Gi y ttc Phe gt t Val gac Asp 135 ctg aaa Lys gac Asp gct Ala 40 gt a Val1 gaa Glu tac Tyr cga Arg atc Ile 120 ggt Gly acc gag Giu gcc Al a ttg Leu cga Arg ttc Phe caa Gin ggt Gly 105 gac Asp ga a Giu ga a Glu atc Ile 10 acc Thr gaa Glu a tg Met ttt Phe gct Al a 90 gca Ala Ct t Leu atc Ile a cc Thr ggt Gly aac Asn gtt ValI t cg Se r ga a Glu atc Ile 99c Giy cta Leu ga a Glu ct a Leu gtt Val1 acc Thr acc Thr att Ile gac Asp gga GI y 125 tcc Se r a cc Thr ccc Pro ct c Leu gca Al a cag Gin Gi y cct Pro act Thr t ca Ser cga atc atg cgc agc gac cca Arg Ile Met Arg Ser Asp Pro Arg Leu Thr 150 ccc gac Pro Asp tgaaaccgaa gtggaaatcg ccc <210> 106 <211> 162 <212> PRT <213> Corynebacterium glutamicum <400> 106 Giu Val Thr Pro Giu Gly Phe Lys Glu Ilie Thr Arg Giu Asn Thr Ile 1 5 10 Val1 Ala Gi u Arg Leu Giu Asp Phe Gin 145 Pro WO 01/00804 Arg Leu Gly Ile Glu Arg Thr His Giy Asp Ala Ser Ser Lys Ile Giu Ala Leu 100 Gin Gly Pro 115 Ile Vai Gly 'J 130 Met Gly Cys N Asp Lys Thr ValI As n Arg Lieu Phe ~hr ~al Gly Val Arg Val Glu Ala Arg Asp 70 Pro Gly Ser Phe Cys Val Tyr Asp 135 Arg Leu 150 Ala Thr 25 Leu Giu Axg Met Phe Phe Gin Ala Gly Ala 105 Asp Leu Giu Ile Giu Arg PCT/IBOO/00922 Gly Asn Val Se r Giu Ile Giy Leu Ile 155 Asp Giu Ser Arq Ser Leu 110 Ser His Se r <210> 107 <211> 654 <212> DNA <213> Corynebacterium giutamicum <220> <221> CDS <222> (631) <223> RXS01835 <400> 107 tcaacatcta ttcctcctgc gatttgcatg ggatatatat ttcctgcgtg aatacacttt ccccgcgcct tcgcaaagct tgg gca cac cgc cac cac qta cgc aaa ggc ggt Trp Ala His Arg His His Val Arg Lys Giy Gly 15 agc cat ctt tat tca gtg atg tac ttg ctg qcc Ser His Leu Tyr Ser Val Met Tyr Leu Leu Ala 30 gaa gat gtg ctc atc gcc ggg ctg ctc cac gac taaaaattct agccgaaagt atg aat act gcc gcg Met Asn Thr Ala Ala 1 gga att ccg tat gtc Gly Ile Pro Tyr Val agc gtc act aat gat Ser Val Thr Asn Asp acc ctc gaa gac gta 115 163 211 259 WO 01/00804 WO 0100804PCT/IBOO/00922 Giu Asp Val Leu Ile Ala Gly Leu Leu His Asp Thr Leu Glu Asp Val ccc gag Pro Glu gtg cgc Val Arg aaa gcg Lys Ala tta gag Leu Giu tcc atc Ser Ile ttt aac Phe Asn 135 cag ata Gin Ile 150 gaa tac Glu Tyr gag ttg Glu Leu cgt gcc Arg Ala gct gtc Ala Val 105 ttg gat Leu Asp 120 gct ggc Ala Gly tct ctc Ser Leu aa t Asn gtg Val1 gac Asp tta Leu gac Asp aaa Lys cag Gin tct gcc Ser Ala 60 gaa gag Giu Glu 75 gct tac Ala Tyr atc tcc Ile Ser ctt gaa Leu Giu gag cag Giu Gin 140 cgc tta Arg Leu 155 ca a Gin ct C Leu ctc Leu a cc Thr ata Ile 125 caa Gin ggg Gly gaa gct Glu Ala aaa cag Lys Gin cac ctc His Leu 95 gat aaa Asp Lys ggt gaa Gly Glu tgg tgg Trp Trp aat gag Asn Giu 160 gat Asp ccc Pro agc Ser ctg Leu gat Asp tat Tyr 145 ttg Leu ggt Gly aaa Lys ggt Gly aat As n 115 tgg Trp gag Giu aaa ccg Pro agc Se r gcc Ala 100 ctc Leu caa Gin gt t Val caa Asn Lys Gin Leu ggg ttg tgc gtc gaa aag etc tta aag caa agc gee taggcgctcg Giy Leu Cys Val Giu Lys Leu Leu Lys Gin Ser Ala 170 175 gcggcgtcga taa <210> 108 <211> 177 <212> PRT <213> Corynebacterium giutamicum <400> 108 Met Asn Thr Ala Ala Trp Ala His Arg His His Val Arg Lys Gly*Gly 1 5 10 Gly Ilie Pro Tyr Val Ser His Leu Tyr Ser Vai Met Tyr Leu Leu Ala 25 Ser Val Thr Asn Asp Giu Asp Val Leu Ile Ala Gly Leu Leu His Asp 40 Thr Leu Giu Asp Val Pro Glu Glu Tyr Asn Ser Ala Gin Leu Giu Ala 55 Asp Phe Gly Pro Arg Val Arg Giu Leu Val Giu Glu Leu Thr Lys Gin WO 01/00804 WO 0100804PCT/IBOO/00922 Pro S er Leu Asp Tyr 145 Leu Trp Ser Met Arg Tyr Leu 165 Asp 90 Leu Asp Lys Gin Glu 170 His Asp Gly Trp As n Gin 175 <210> 109 <211> 1050 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> (101)..(1027) <223> RXS02497 <400> 109 tcgatgccgc cgctggcgaa. gactcgggga aacctaaaaa gattcacact ttgccaccct agaccgtcta acctttaggt tta Leu ccc Pro ct Leu aac Asn agc aat Ser Asn ccc acc Pro Thr ctt gat Leu Asp tca gca Ser Ala act gtc Thr Val ccg atq Pro Met gac icc Asp Ser gtc ggg Val Gly cac cta His Leu 15 aqc aat Ser Asn ggg gcg Gly Ala gaa gca Glu Ala taccgaagaa gaatttgacc gtg aga tta ggt gta.
Val Arg Leu Gly Val 1 gca qta gac gcg cgt Ala Val Asp Ala Arg cgt acc cca ctg cgc Arg Thr Pro Leu Arg tcc gaa aag ggc atc Ser Glu Lys Gly Ile gac cta gcg aaa acg Asp Leu Ala Lys Thr WO 01/00804 WO 0100804PCT/IBOO/00922 etc ggc tge get gaa ctg atg cca ttt Leu Gly Cys Ala Glu Leu Met Pro Phe get aca tcg gca gtc cgc Ala Thr Ser Ala Val Arg gcC Ala gt C Val1 etc Leu etc Leu t cc Ser 150 cac His ct g Leu cgc Arg cyc Arg cac His 230 ttt Phe aqe Ser gct acc Thr cgc Arg gca Ala gac Asp 135 cc a Pro aac As n cg C Arg acc Thr acc Thr 215 gt C V/al atc Ile tcg 3er ;cg aac Asn ctg Leu gtt Val1 120 ate Ile gac Asp tgg Trp gat Asp eta Leu 200 ct g Leu ace Thr tca Ser gat Asp atg agc Sei tec Ser 105 cga Arc gt Gly ct c Leu ttc: Phe tat Tryr 185 gyg GI y gca Al a cga Arg cga Arg Cgg krg 2 65 :gt -gac *Git -atc Sle cgt Arg ggc Gly *gcg Ala gac Asp 170 atc Ile ccc Pro ega Arg acc Thr a tg Met 250 tca Ser gcg Ala 75 gca gtg Ala Val ctt tee Leu Ser tgg tat Trp Tyr ggc tcc Gly Ser 140 ttc tea Phe Ser 155 acc gat Thr Asp gat gcg Asp Ala gcg cgc Ala Arg ctg act Leu Thr 220 etc ac Leu Thr 235 act geg Thr Ala cat cag His Gin ttg gat Leu Asp etc Leu gt GI y gga Gly 125 ctg Leu ctg Leu c ca Pro gaa Glu ct g Leu 205 ggt Gly y cg Ala gcg ate Ile att Ile gac As: ga a Git 110 t gg T rp gaa Glu ga t Asp ccg Pro ct t Leu 190 yea Al a gct Ala ecg Pro gac Asp gtg Val1 270 gac Asp eac His 95 gae Asp tee Ser cta Leu et g Leu gca AJla 175 gca Ala gtg Val1 gcy Ala gg t Gly eye Arg 255 gea Ala aag Lys 80 gtg Val gaa Glu gca Ala tee Ser gt Gly 160 cg t Arg gaa Glu gga Gly ccc Pro ct g Leu 240 get Ala Gly gta la 1 gag Glu gca Al a gyg Gly tee Se r 145 gcg Ala aag Lys ccc Pro aca Thr tea Ser 225 eye Arg gag Glu geg Al a gaa Glu aag Lys Icqc Arg ege Arg 130 gga Gly gge Gly aaa Lys gc Ala tee Ser 210 tee Ser cay Gin etg Leu eta Leu att Ile gaa Glu C aa Gln 115 ata Ile ace Th r ege Arg ate Ile eye Arg 195 aaa Lys gca Ala ctg Leu ga a Glu gt t V/al 275 tgt :ys ace Thr 100 act Thr act Thr gae Asp ttg Leu aac Asn 180 cay Gin act Thr gga Gly ate Ile ggt Gi y 260 geg Ala ceg Pro tee Ser 99C Gly tte Phe aac Asn gaa Glu ac Th r 165 etc Leu aty Met tte Phe cc a Pro yea Al a 245 ate Ile gaa Giu t gg Trp 355 403 451 499 547 595 643 691 739 787 835 883 931 979 1027 Ala Ala Met Arg 280 285 290 gea ctt cyt yaa ggt ytg ate etc ace agg ate yae aaa gga etc gag WO 01/00804 Ala Leu Arg Glu Gly Val Ile Leu Thr Arg Ile Asp Lys Gly Leu Glu 295 300 305 taacatttac ccggaaagga gtt <210> 110 <211> 309 <212> PRT <213> Corynebacterium glutarnicum <400> 110 Val Arg Leu Gly Val Leu Asp Val Gly Ser Asn Thr Val His Leu Val PC T/ BOO/00922 1050 1 Ala Vai Arg Thr Ser Glu Asp Leu Ser Ala Giu Lys Ala Arg Gly Arg 130 Ser Gly 145 Ala Gly Lys Lys Pro Ala Thr Ser 210 Asp Ala Pro Leu Lys Gly Ala Lys Val Arg Giu Thr 100 Gin Thr 115 Ile Thr Thr Asp Arg Leu Ile Asn 180 Arg Gin 195 Lys Thr 5 Arg Pro Arg Leu Ilie Asn Thr Leu 70 Ser Ala Gly Val Phe Leu Asn Leu Glu Ser 150 Thr His 165 Leu Leu Met Arg Phe Arg Gly Val Lys 55 Gly Thr Arg Al a Asp 135 Pro Asn Arg Thr Thr Gly Glu Leu Cys Asn Leu Val1 120 Ile Asp T rp Asp Leu 200 Leu His 25 Leu Th r Al a Ser Ser 105 Arg Gly Leu Phe Tyr 185 Gly Al a Pro Leu Ser Giu G iu Ile Arg Gly Al a Asp 170 Ile Pro Arg Thr Asp Ala Leu Ala Leu Trp GI y Phe 155 Thr Asp Ala Leu Pro
ASP
Val1 Met Val1 Ser Tyr Ser 140 Ser Asp Ala Arg Thr 220 Ser Gly Glu Phe Asp Giu 110 Trp Gi u Asp Pro Leu 190 A1a Al a Ser Ser Ala Gly Pro His Val Thr Arg Thr Leu Thr Ala Pro Gly Leu WO 01/00804 Arq Gin Leu Ile Giu Leu Glu Gly 260 Ala Leu Val Ala 275 Giu Ilie Cys Pro 290 Asp Lys Gly Leu 305 <210> 111 <211> 534 <212> DNA <213> Corynebact <220> <221> CDS <222> (101)..(51 <223> RXS02972 <400> 111 acctacgacg gtgaa gaacgaatca tgcgc PCT/1B00i00922 Ala Phe Ile Ser Arg Met Thr Ala Ala Asp Arg Ala 245 250 255 Ile Ser Ser Asp Arg Ser His Gin Ile Val Ala Gly 265 270 Giu Ala Ala Met Arg Ala Leu Asp Ile Asp Lys Val 280 285 Trp Ala Leu Arg Giu Gly Val Ilie Leu Thr Arg Ile 295 300 Glu erium giutamicum 1 atcct aggctcccac tcaacccaaa tgggatgcgt gcgcctgacc agcga cccacccqac tgaaaccgaa gtg gaa atc gcc cgc Val Giu Ile Ala Arg 1 gaa cgc atc cag gaa gta aaa gcc atc gtc cca att Giu Arg Ile Gin Glu Val Lys Ala Ile Val Pro Ile is acc ttt gtg gga tgc gca ggc acc ttc acc aca. atc Thr Phe Val Giy Cys Ala Gly Thr Phe Thr Thr Ile caa ggc cta gaa agc tac gac cgc gac gcg atc cac Sin Gly Leu Glu Ser Tyr Asp Arg Asp Ala Ile His s0 3ac ttc gat gca ctg cga gtt gtc acc gat gag atc ksn Phe Asp Ala Leu Arg Val Vai Thr Asp Giu Ile catca cag cgc gcc agc aac cca gtt qtt gatca 3er Ser Gin Arq Ala Ser Asn Pro Vai Val Asp Pro 75 80 Itc atc ggt ggc gga tcc gtt gtt gtc caa gca gcg fal Ile Gly Gly Gly Ser Val Val Val Gin Ala Ala qn 91;100 gac Asp t ca Ser tcc Ser ctc Leu att Ilie ggt Gly 115 163 211 259 307 355 403 WO 01/00804 atc gac tta qcc tcc aaa gaa gcc ggt gta gac tac atc att att tcc Ile Asp Leu Ala Ser Lys Glu Ala Gly Val Asp Tyr Ile Ile Ile Ser 105 110 115 gaa aaa gac atc ctc gac ggc ctc atc ctt ggc ctg gta gaa gcc gac Giu Lys Asp Ilie Leu Asp Gly Leu Ile Leu Giy Leu Val Giu Ala Asp 120 125 130 tct ttg aag aaa tagqacccta gttttaaacc act Ser Leu Lys Lys 135 <210> 112 <211> 137 <212> PRT <213> Corynebacterium giutamicun <400> 112 Val Glu Ile Ala Arg Asp Tyr Val Ala Giu Arg Ile Gin Giu Val Lys 1 5 10 Ala Ile Val Pro Ile Ser Lys Ala Lys Thr Phe Vai Gly Cys Ala Gly 25 Thr Phe Thr Thr Ile Ser Ala Trp Val Gin Gly Leu Glu Ser Tyr Asp 40 Arg Asp Ala Ile His Leu Ser Ala Leu Asn Phe Asp Ala Leu Arg Val 55 Val Thr Asp Glu Ilie Ile Ser Glu Ser Ser Ser Gin Arg Ala Ser Asn 70 75 Pro Val Vai Asp Pro Giy Arg Ala Asp Val Ile Gly Gly Gly Ser Val 90 Val Val Gin Ala Ala Ile Asp Leu Ala Ser Lys Giu Ala Gly Vai Asp 100 105 110 Tyr Ilie Ile Ile Ser Glu Lys Asp Ile Leu Asp Gly Leu Ile Leu Gly 115 120 125 Leu Val Giu Ala Asp Ser Leu Lys Lys 130 135 <210> 113 <211> 636 <212> DNA <213> Corynebacteriun giutamicum <2 <221> CDS <222> (613) <223> RXA02159 PCTJIBOO/00922 451 499 534 WO 01/00804 <400> 1.13 tgatggaeca gegtccaaag ttttcgatga, agcagaaaac PCTIIBOO/00922 cgcctccacg ctcagaaagc actgctggtg tggctgctgg ccaaccagcc gaggtaagac atg tcc ctt Met Ser Leu ace Thr caa Gi~n gt a ValI gce Ala ccc Pro gce Ala gat Asp ege Arg gtg Val1 ttc Phe 150 tea Ser c tc Leu ctg Leu ttg Leu ggg Gi y gaa Gi u ctg Leu ccg Pro 120 ctg Leu ctc Leu ceg gaa.
Pro Glu ttg cag Leu Gin gaa ttg Glu Leu cga gat Arg Asp ege gee Arg Ala 75 ctc cgg Leu Arg gtt tct Val Ser gga gct Gly Ala gaa gtc Giu Val cgt gat Arg Asp 155 aac Asn at t Ile ctg Le u etc Leu tac Tyr ggt Gly aca Thr gc Al a gt t Val1 140 ccg tta.
Leu ttg Leu at g Leu 45 gat Asp t ac Tyr ccg Pro gat Asp cag Gin 125 ggc Gi y ctc aat Asn ga c Asp ga t Asp ga Giu gcg Al a t cg Ser cat His 110 tac Tyr ace Thr a ca ccc Pro 15 aaa Lys gas Glu c te Leu gte Val1 gag Glu 95 tea Ser atg Leu ate Ile ggt Gly 1 gtg act cgc Val Thr Arg esa ass. gtc Gin Lys Val gga ate gat Giy Ile Asp ggt gca ege Gly Ala Arg ggc eca. gta Gly Pro Val 80 sag ctg ega Lys Leu Arg gge sac ate Gly Asn Ile ga agt ttc Ala Ser Phe 130 get ggt gat Ala Gly Asp 145 aaa gas cta Lys Glu Leu 160 act Thr ace Thr ate Ile aag Lys ga t Asp age Arg gag Al a 115 ate Ile gac Asp ggt Gly gge tea Gly Ser ges. ega Ala Arg age eag Ser Gln ace cag Thr Gln gtt ege Val Arg age ate Ser Ile atg ctt Met Leu 100 atg ctg Met Leu gat agg Asp Arg ace gtt Thr Val gsa tta Glu Leu Pro Leu Thr etc age ggg Leu Ser Gly ege ace act tasagegce etagtteaag get Arg Thr Thr 170 <210> 114 <211> 171 <212> PRT <213> Corynebacterium glutalnicum WO 01/00804 <400> 114 Met Ser Leu Gly Ser Thr Pro Ser Thr Pro Glu Asn Leu Asn Pro Val PCT/IBOO/00922 1 Thr Lys Ile Al a Pro Leu Asn Ser Gly 145 Glu 5 Ala Arg Ser Gin Thr Gin Vai Arg Ser Ile Met Leu 100 Met Leu Asp Arg Thr Val Glu Leu 165 10 Leu Glu Arg Arg Leu Val Gly Glu Arq Thr 170 Gin Leu Asp Al a Arg Ser Al a Val1 Asp 155 Thr <210> 115 <211> 486 <212> DNA <213> Corynebacteriun glutamicum <2 <221> CDS <222> (101)..(463) <223> RXA02201 <400> 115 tctaccagcc aaatcatcaa ctcatagcga aggaatcaac ttcatgaata atcaaccatc agtacttttc gtttgcgtcg gcaatggtgg aaaatctcaa atg gcc gca gcg cta 115 Met Ala Ala Ala Leu 1 gcc aaa aaa cat gcC ggg gac gct ctc aaa gtt tat tca gct ggc aca 163 Ala Lys Lys His Ala Gly Asp Ala Leu Lys Val Tyr Ser Ala Gly Thr 15 aag cca ggt acg aaa tta aat caa cag tcc ctt gat tcc att gct gaa 211 Lys qtt Val tta Leu cta Leu gac Asp gtc Val1 acc Thr WO 01/00804 Pro Giy Thr Lys Leu Asn Gin Gin Ser Leu 30 qgc gca gat atg tct caa ggg ttt cca aaq Gly Ala Asp Met Ser Gin Gly Phe Pro Lys 40 att aag cga gta gac cgc gtg gtc att ctt Ile Lys Arg Val Asp Arg Vai Val Ile Leu 55 60 gaa aig cct atc gat gca aac ggc ata cta Glu Met Pro Ile Asp Ala Asn Gly Ile Leu 75 gaa ccc tct gaa cgt gga att gaa ggt atg Glu Pro Ser Glu Arg Gly Ile Giu Gly Met cga gat gat att gac gcc cga gtc caa aac Arg Asp Asp Ile Asp Ala Arg Val Gin Asn 105 110 caa aac gca tagcagtttt ctaatctcac aca Gin Asn Ala 120 Asp ggC Gi y ggt Gi y cag Gin gaa Giu ctc Leu Asp Asn Gin Ax g Ala Gly Ala Ile gac Asp gaa Giu tgg Trp atg Met gct Al a 115 PCT/IBOO/00922 <210> 116 <211> 121 <212> PRT <213> Coryriebacterium glutamicum <400> 116 Met Ala Ala Ala Leu Ala Lys Lys His 1 Tyr Ser Ala Gly Thr Lys Pro Gly Thr 25 Asp Ser Ile Ala Glu Val Gly Ala Asp Gly Ilie Asp Gin Giu Leu Ile Lys Arg 55 Gly Ala Giu Ala Gin Leu Glu Met Pro Gin Arg Trp Val Thr Asp Glu Pro Ser Giu Arg Met Arg Leu Val Arg Asp Asp 100 105 Leu Val Ala Giu Leu Thr Gin Asn Ala 115 120 Leu Gin Phe Val Gly Glu Vai 110 WO 01/00804 WO 0100804PCT/IBOO/00922 <210> 117 <211> 510 <212> DNA <213> Corynebacteriun giutamicum <220> <221> CDS <222> (101)..('287) <223> RXA00599 <400> 117 gaacgatcgg ccctttgatt gaagtcccag tattagtcgg attggtttat gtcatgttgt ggcttggacc aaaaatcttt aaaaaggaga atgcaggatc atg aaa tca gtt ttg Met Lys Ser Val Leu 1 ttt gtg tgc gtc ggt aat ggc gga aaa tca cag atg gcg gcg gcg ctg Phe Val Cys Val Gly Asn Gly Gly Lys Ser Gin Met Ala Ala Ala Leu 15 gca cag aag tat gca tca gat tca gta gag atc cat tct gct gga ace Ala Gin Lys Tyr Ala Ser Asp Ser Val Glu Ile His Ser Ala Gly Thr 30 aag cct gca cag ggg cta aac caa ttg tct gtg gaa tcc atc gct gag Lys Pro Ala Gin Gly Leu Asn Gln Leu Ser Val Giu Ser Ile Ala Glu 45 gtg ggc gct gat atg tcg caa gga att ccc aaa gcg ate gat ccg gag Val Gly Ala Asp Met Ser Gin Gly Ile Pro Lys Ala Ile Asp Pro Glu 60 ctg ctg cgc act gtc: gat cgt gtg gtt att ttg ggc: gat gac gca cag Leu Leu Arg Thr Val Asp Arg Val Val Ile Leu Gly Asp Asp Ala Gin 75 80 gta gat atg cct gaa tct gca cag ggc gct ctt gag cgt tgg tca att Val Asp Met Pro Glu Ser Ala Gin Gly Ala Leu Giu Arg Trp Ser Ile 95 100 gag gaa ccg gat gct caa ggt atg gaa cgt atg cgt att gtg cgg gat Giu Giu Pro Asp Ala Gin Gly Met Giu Arg Met Arg Ile Val Arg Asp 110 115 115 163 211 259 307 355 403 451 cag atc gat aac Gin Ilie Asp Asn 120 aaaaggggca tgt <210> 118 <211> 129 <212> PRT cga gtc caa Arg Vai Gin gct ttg cta gcg gga Ala Leu Leu Ala Gly taagcgccga WO 01/00804 <213> Corynebacteriun giutamicwn <400> 118 Met Lys Ser Val Leu Phe Val Cys 1 Met Ala Ala Ala Leu Ala Gin Lys His Ser Ala Gly Thr Lys Pro Ala Giu Ser Ilie Ala Glu Val Gly AlaJ 55 Ala Ile Asp Pro Giu Leu Leu Arq Gly Asp Asp Ala Gin Val Asp Met 1 Glu Axrg Trp Set lie Giu Glu Pro I 100 Arg Ile Val Arg Asp Gin Ile Asp 115 120 Gi y PCTIIBOO/00922 Gly Asp As n Gin Arg Ala GI y Gin <210> 119 <211> 1221 <212> DNA <213> Corynebacterium glutamicun <220> <221> CDS <222> (101)..(1198) <223> RXA00600 <400> 119 cggagttaat gagcggtagg tggatgggtg cggtcatgtc catcgatatt gaaggtattt ttatatcggc aaacatcaat ctc atg acc ctt act aaa gag cat tcg aca cct Leu Met Thr Leu Thr Lys Giu His Ser Thr Pro 15 atg tcg ttt ctt gac cgc tgg tta gct gcc tgg Met Ser Phe Leu Asp Arg Trp Leu Ala Ala Trp 30 gct gct ggg ttg tta atc ggc aag gte ttt cca cgtcattata tattgacgca atg att gaa ggc tgg Met Ile Giu Gly Trp 1 cga gcg gct ggc tea Arg Ala Ala Gly Ser att ttc ttg get atg Ile Phe Leu Ala Met gga att ggg gcg ctt WO 01/00804 WO 0100804PCTIBOO/00922 Ala Ala Gly Leu Leu Ile Gly t tg Leu t tg Leu act Thr tig Leu ttt Phe ct t Leu ggt Gi y 150 cag Gin ccc Pro tea Ser gga Gly tac Tyr 230 ttg Leu age Ser atc Ile aaa Lys aac Asn ct t Leu geg Ala 135 gac Asp ate Ile teg Ser ate Ile gtt Val 215 gag G lu cta Leu geg Ala gte ValI gaa Glu tgg Trp cca Pro 120 cge Arg egg Arg ctt Leu tgg Trp gtg Val 200 tta Leu gac Asp tac Tyr gtg ValI atg Met ate Ile atc Ile 105 ga t Asp tgt Cys gaa Glu atg Met ctg Leu 185 act Thr tet Ser aeg Thr a ca Thr gaa Giu atg Met age Ser gtt Val1 caa Gin atc Ile gea Ala ttc Phe 170 gga GI y tee Ser ege Arg ttc Phe att Ile 250 att Ile tat Tyr 75 aca Th r gga Gly c ca Pro geg Ala act Thr 155 ggt Giy tta Leu gtt Val Val1 ct g Leu 235 ;t t fa 1 ggt GI y 60 cca Pro gac Asp cca Pro gag Glu atg Met 140 get Al a gtg ValI gac Asp ete Leu att Ile 220 cct Pro et g Leu Lys 45 gga Gly cct Pro ege Arg gca Aila et t Leu 125 gtt Val1 gt g Val1 ett Leu ace Thr gtg Val 205 ggt Giy aag Lys etg Leu Val Phe Pro Gly Ile Gly Ala Leu att Ile ttc Leu get Al a ct t Leu 110 ege Arg t tg Leu etg Leu ggt Gly aeg Thr 190 tte Phe gaa Glu att Ile ttt Phe tee Ser gee Ala tc *Leu 95 a tg *Met act Thr gta Val gtt Val tgg Trp 175 teg Se r t tg Leu aaa Lys tea Ser tcg Ser 255 att Ile aag Lys 80 atg Met ttt Phe 99g Gly tgg Trp gca Al a 160 ttt Phe gtg ValI Gly aea Thr ccc Pro 240 ttg Leu cca Pro gtg Val1 gtg Val1 age Ser eta Leu agt Ser 145 ate Ile t ac Tyr act Thr at a Ile aag Lys 225 ttg Leu cag Gin att get Ile Ala egc tac Arg Tyr gtg tcg Val Ser ctg geg Leu Ala 115 att ate Ile Ile 130 gat etc Asp Leu aac teg Asn Ser etg cag Leu Gin ttc tet Phe Ser 195 eca ctt Pro Leu 210 gga egg Gly Arg geg etg Ala Leu ggg gat Gly Asp ate Ile gae Asp at t Ile 100 tgg T rp, gtg Val1 get Al a gtg Val1 att Ile 180 gtg Val gta Val ege Arg att Ile ga a Glu 260 ggt Gly aaa Lys atg Met ct g Leu gg e Gly t gt Cys t te Phe 165 ctt Leu gta Val1 get Ala tgg Trp gge Gly 245 ate Ile 307 355 403 451 499 547 595 643 691 739 787 835 883 aca geg eag ect tgg aca gta get egt ctt gca ttg Thr Ala Gin Pro Trp Thr Val Ala Arg Leu Ala Leu eeg etg ctg atg Pro Leu Leu Met WO 01/00804 265 270 tac ttt gtg ggc atg ttt ttc att tcc Tyr Phe Val Giy Met Phe Phe Ilie Ser 280 285 ggg tta act tat gag cga gct gct tcc Gly Leu Thr Tyr Glu Arg Ala Ala Ser 295 300 aac aac ttt gaa tta gcg att gcg gta Asn Asn Phe Giu Leu Ala Ile Ala Val 310 315 aca tca ccg cag gca tta gct gga acg Thr Ser Pro Gin Ala Leu Aia Gly Thr 330 cca gta tta gtc gga ttg gtt tat gtc Pro Val Leu Val Gly Leu Val Tyr Val 345 350 atc ttt aaa aag gag aat gca gga tca Ile Phe Lys Lys Glu Asn Ala Gly Ser 360 365 tgc <210> 120 <211> 366 <212> PRT <213> Corynebacterium giutarnicum <400> 120 Met Ilie Giu Gly Trp Leu Met Thr Leu 1 Arg Ala Ala Gly Ser Met Ser Phe Leu Ile Phe Leu Ala Met Ala Ala Gly Leu 40 Giy Ile Gly Ala Leu Leu Ser Ala Val Pro Ilie Ala Ilie Gly Leu Ile Val Met 70 Val Arg Tyr Asp Lys Thr Lys Glu Ile Val Val Ser Ile Met Leu Asn Trp Ile 100 105 Ser Leu Ala Trp Leu Phe Leu Pro Asp PCTIBOO/00922 275 ctg gtg gta tcc aaa ctg Leu Val Val Ser Lys Leu 290 gtg tct ttt act gca gca Val Ser Phe Thr Ala Ala 305 tcg atc gga acc ttt ggt Ser Ile Giy Thr Phe Gly 320 atc ggc cct ttg att gaa Ile Gly Pro Leu Ile Glu 335 340 atg ttg tgg ctt gga cca Met Leu Trp Leu Gly Pro 355 tgaaatcagt tttgtttgtg 979 1027 1075 1123 1171 1218 1221 Lys Arg Ilie Ile Tyr Thr Gly Pro His Leu Lys Gly Pro Arg Al a Leu WO 01/00804 WO 0100804PCTIIBOO/00922 115 120 125 Leu Ile Ile Val Gly Leu Ala Arg Cys Ile Ala Met Val Leu Val Trp 130 135 140 Ser Asp Leu Ala Cys Gly Asp Arg Glu Ala Thr Ala Val Leu Val Ala 145 150 155 160 Ile Asn Ser Val Phe Gin Ile Leu Met Phe Giy Val Leu Gly Trp Phe 165 170 175 Tyr Leu Gin Ile Leu Pro Ser Trp Leu Gly Leu Asp Thr Thr Ser Val 180 185 190 Thr Phe Ser Val Val Ser Ile Val Thr Ser Val Leu Val Phe Leu Gly 195 200 205 Ile Pro Leu Val Ala Giy Val Leu Ser Arg Val Ile Gly Giu Lys Thr 210 215 220 Lys Giy Arg Arg Trp Tyr Glu Asp Thr Phe Leu Pro Lys Ile Ser Pro 225 230 235 240 Leu Ala Leu Ile Gly Leu Leu Tyr Thr Ile Vai Leu Leu Phe Ser Leu 245 250 255 Gin Gly Asp Giu Ile Thr Ala Gin Pro Trp Thr Val Ala Arg Leu Ala 260 265 270 Leu Pro Leu Leu Met Tyr Phe Vai Gly Met Phe Phe Ile Ser Leu Val 275 280 285 Val Ser Lys Leu Ser Gly Leu Thr Tyr Giu Arg Ala Ala Ser Val Ser 290 295 300 Phe Thr Ala Ala Gly Asn Asn Phe Giu Leu Ala Ile Ala Val Ser Ile 305 310 315 320 Giy Thr Phe Gly Ala Thr Ser Pro Gin Ala Leu Ala Gly Thr Ile Gly 325 330 335 Pro Leu Ile Glu Val Pro Val Leu Val Gly Leu Val Tyr Val Met Leu 340 345 350 Trp Leu Gly Pro Lys Ile Phe Lys Lys Glu Asn Ala Gly Ser 355 360 365 <210> 121 <211> 1233 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> (1210) <223> RXA02200 WO 01/00804 <400> 121 attgtgtgga gagtggtcat aaatccacta tatattgacg PCTIIBOO/00922 aatgtcgata ttgaaagtat tttgaatatc gacaggtatc aatataccqa aaggtgtcgc atg aca aac tca act Met Thr Asn Ser Thr cag Gin cca Pro agc Ser atc Ile t tg Leu cat His tta Leu cga Arg ttg Leu ctc Leu 150 9gC Gi y acc Thr acg cgg Thr Arg ctt tgg Leu Trp gtt tcg Val Ser tcc ttg Ser Leu gcc aaa Ala Lys ttg atg Leu Met atg ttc Met Phe acc ggc Thr Gly 120 gtt tgg Val Trp 135 gta gcc Val Ala tgg ttc Trp Phe acc gct Thr Ala gcc Ala att Ile gga Gi y cc a Pro gtt Val ggc Gly gcg Al a 105 ctg Leu tct Se r att Ile tat Tyr caa Gin 185 aag Lys att Ile ctc Leu atc Ile Arg gtg Val1 ct a Leu att Ile gat Asp aat Asn ctg Leu 170 ttcI Phe cca Pro ttg Leu t ca Ser gct Ala tat Tyr 75 tca Se r gct Al a at Ile a tg Met tca Ser 155 :aa Gln tct 3er 9CC Ala gcg Ala ggc Gi y ta Leu 60 gac Asp ctc Leu t gg Trp gta Val1 t cc Ser 140 gt t Val gt t Val tc Phe cga Arg atg Met ttt Phe 45 ggc Gly aaa Lys att Ile ttg Leu gga Gly 125 i gt Cys ttt Phe tta Leu Lgg rrp at c Ile gcg Ala 30 cta Leu ci c Leu act Thr ctc Leu ttc Phe 110 ci c Leu gga Gly caa Gin cca Pro tca Ser 190 t ca Ser 15 ttt Phe ggc Gly ctt Leu aaa Lys aat Asn 95 ci c Leu gca Ala gac Asp gtc Val1 icc Se r 175 at Ile tt Phe 9gg Gly gca Al a gt a Val1 caa Gin 80 t gg Trp cca Pro cga Arg cgc Arg gca Al a 160 tgg Trp gtg Val 1 ctt Leu cia Leu atg Met atg Met at Ile gtg Val gac Asp tgt Cys gag Glu 145 atg Met cta Leu act Thr ga t Asp ttt Phe gaa Glu atg Met gcc Ala gtg Val caa Gin at t Ile 130 gct Al a ttt Phe gga Gly t cg Ser aaa Lys tta Leu gtc Val1 tac Tyr act Thr ggt Gly ccg Pro 115 gcg Al a aca Thr ggt Gly tta Leu gii Val1 195 i ac T yr ggc Gly gga Gly cca Pro ga t Asp cct Pro 100 gaa Glu atg Met gca Ala gca Ala c ca Pro 180 tig Leu att Ile Arg 9gg Gly ccg Pro aag Lys gcc Ala tta Leu gtc Val1 gt Val ct t Leu 165 act Thr gt g Val1 163 211 259 307 355 403 451 499 547 595 643 691 739 ttc ctc gga ata cct Cta ctt gct gga gtt tic tcg cga att att ggc WO 01/00804 WO 0100804PCTJIBOO/00922 Phe Leu Gly Ilie Pro Leu Leu Ala Gly Val Phe Ser 200 gaa aag atc Glu Lys Ilie 215 atc tct cca Ile Ser Pro 230 ttt tca ttg Phe Ser Leu cgt ctc gcg Arg Leu Ala tca ctc att Ser Leu Ilie 280 tcc gtc tct Ser Val Ser 295 gtg tcg atc Vai Ser Ilie 310 acg att ggt Thr Ilie Gly gcc atg ctg Ala Met Leu 205 aag Lys ttt Phe caa Gin ata Ile 265 9g Ala ttc Phe gga Gly ccc Pro tgg Trp 345 gga cgt Giy Arg gca cta Aia Leu 235 ggt gat Giy Asp 250 cca ttg Pro Leu ica aaa Ser Lys act gca Thr Ala acg ttt Thr Phe 315 ttg att Leu Ile 330 cta ggc Leu Gly gag Giu 220 atc Ile ca g Gin gt t Val1 ct a Leu gct Ala 300 9gc Gly gaa Giu ccc Pro tgg Trp ggt Gi y atc Ile atc Ile tct Ser 285 ggc Giy gca Ala att.
Ile aag Lys tat Tyr ct g Leu gt C Val tat Tyr 270 ggc Giy aac Asn act Th r cca Pro ttg Leu 350 gaa Glu ctt Leu t ct Ser 255 ttc Phe at g Met aat Asn t ct Ser gta Val 335 ttc Phe Arg 210 ttc Phe atc Ile t gg Trp atg Met gca Al a 290 ct t Leu gct Gly gac Asp Ile Ile Gly ct t Leu gt c Val1 gct Al a ttt Phe 275 aag Lys gcg Ala atg Met t tg Leu Ccc Pro 355 787 835 883 931 979 1027 1075 1123 1171 1220 1233 cca tca tca gct cgt tct acc agc caa atc atc aac tca tagcgaagga Pro Ser Ser Ala Arg Ser Thr Ser Gin Ile Ile Asn Ser 360 365 370 atcaacttca tga <210> 122 <211> 370 <212> PRT <213> Corynebacterium giutamicum <400> 122 Met Thr Asn Ser Thr Gin Thr Arg Aia Lys Pro Ala Arg Ile Ser Phe 1 5 10 Leu Asp Lys Tyr Ile Pro Leu Trp Ile Ile Lea Ala Met Ala Phe Gly 25 WO 01/00804 WO 0100804PCTIBOOIOO922 Leu Met Met Ile Val Asp Cys Giu 145 Met Leu Thr Ser Lys 225 Thr Pro Gly Tyr Glu 305 Phe Leu Gly Arg Ser Val Ser Gly Leu Ser Gly Phe Leu Gly Ala Gi u Met Ala Val1 Gin Ile 130 Ala Phe Gi y Ser Arg 210 Phe Ile Trp Met Al a 290 Leu Gly Pro Asp Pro 100 G lu Met Ala Al a Pro 180 Leu Ile Pro Leu Val 260 Phe Ser Ile Gly Pro Lys Ala Leu Val1 Val1 Leu 165 Thr Val Gly Ala Leu 245 Val Ile Al a A-1a Ile Leu 70 His Leu Arg Leu Leu 150 Gly Thr Phe Giu Ile 230 Phe Arg Se r Ser Val 310 Ser Leu Ala Lys Leu Met Met Phe Thr Gly 120 Val Trp 135 Val Ala Trp Phe Thr Ala Leu Gly 200 Lys Ile 215 Ser Pro Ser Leu Leu Ala Leu Ilie 280 Val Ser 295 Ser Ile Pro Ile Val Arg Giy Val Ala Leu 105 Leu Ile Ser Asp Ile Asn Tyr Leu 170 Gin Phe 185 Ile Pro Lys Gly Phe Ala Gin Gly 250 Ile Pro 265 Ala Ser Phe Thr Giy Thr Ala Tyr Ser Ala Ile Met S er 155 Gin Ser Leu Arg Leu 235 Asp Leu Lys Ala Phe 315 Gly Lys Ile Leu Gly 125 Cys Phe Leu Trp Al a 205 Trp Gly Ile Ile Ser 285 Gly Al a Gin Ala Met Ala Gly 325 Thr Ile Gly Pro Ile Glu Ile Pro Val Leu 335 WO 01/00804 Val. Gly Leu Val Tyr Ala Met Leu Trp Leu Gly Pro Lys Leu Phe Pro 340 345 350 Asn Asp Pro Thr Leu Pro Ser Ser Ala Arg Ser Thr Ser Gin Ile Ile 355 360 365 Asn Ser 370 <210> 123 <211> 762 <212> DNA <213> Corynebacteriun giutamicum <220> <221> CDS <222> (101) (739) <223> RXA02202 <400> 123 cgctgaacta acccaaaacg catagcagtt. ttctaatctc acacatcttc aacaccgtt aatctattgg tttccccgta aaatcttcga aaggaagaac atg acc ggg caa gct Met Thr Gly Gin Aia PCT/IBOO/00922 :a gca cca aac ttg Ala Pro Asn Leu gcg ttg acc tat Ala Leu Thr Tyr att ttt gaa tcg Ile Phe Glu Ser cac ctg cca att.
His Leu Pro Ile ctt gcg gta gct Leu Ala Val Ala ttt att tgc gtc Phe Ile Cys Val.
ttg tct cac tat Leu Ser His Tyr 105 cat His caa Gin tat Tyr ttg Leu gaa Glu cac His gcc Al a acc aat Thr Asn gga gtt Gly Val gtg tcg Val Ser gca gaa Ala Giu 60 ggt aag Gly Lys 75 aac gos Asn Ala ggt agt Gly Ser ttg Leu tct.
Ser 30 gcq Ala ttt Phe gct Ala cg t Arg gta ValI 110 aac As n 15 gca Ala aga Arg qct Al a t ca Se r tca Se r 95 gag Glu 1 atc Ile act Thr gca Ala gac Asp gtg Val1 att Ile cgt Arg gaa Giu 20 cgc Arg cat His cac His gt c Val gcg Al a 100 ggt Gly ctg Leu tat Tyr acg Thr gca Al a ct a Leu ttg Leu tct Ser 115 163 211 259 307 355 403 451 115 tta cct gct. tct gsa ati cac ccs ctg gtg ttg gsa att ttg tca gag WO 01/00804 Leu Pro Ala Ser Giu Ile His Pro Leu 120 125 cga gga gtg aac att tct gat gca ttt Arg Gly Vai Asn Ile Ser Asp Ala Phe 135 140 gtt att cgc gca tct gac tat gtc ata Val Ile Arg Ala Ser Asp Tyr Val Ilie 150 155 tgc cca atg tat cca gga aag cac tat Cys Pro Met Tyr Pro Gly Lys His Tyr 170 ccg tca gat gaa ggt gag gac aag ata Pro Ser Asp Giu Gly Glu Asp Lys Ile 185 190 gac ggt cga atc cgc gag ctt tgg aaa Asp Gly Arg Ilie Arg Glu Leu Trp Lys 200 205 taggcagtca aaggtctggc acc <210> 124 <211> 213 <212> PRT <213> Corynebacterium glutamicum <400> 124 Met Thr Gly Gin Ala Ala Pro Asn Leu 1 5 Ile Ala Asn Glu Leu Ala Leu Thr Tyr 25 Thr Ilie Asn Arg Tyr Ilie Phe Giu Ser 40 Ala Lys Ile His Thr His Leu Pro Ile 55 Asp Arg Leu His Ala Leu Ala Val Ala 70 Val Pro Gin Val Leu Phe Ile Cys Val1 Ilie Ala Ser Ala Leu Leu Ser His Tyr I 100 105 Arg Ser Ala Gly Ser Leu Pro Ala SerC 115 120 Giu Ilie Leu Ser Giu Arg Gly Val Asn I PCT/IBOO/00922 Thr Asn Ilie Gly Val Phe Val Ser Leu Ala Glu Gly Gly Lys Val Asn Ala Gly Gly Ser Ser Ile His Pro 125 Ser Asp Ala Leu Ser Ala Phe Al a Arg Val1 110 Leu Phe Asn Ala Arg Ala Ser Se r Glu Val1 Pro WO 01/00804 130 Pro Leu Thr Asp 145 Gly Cys Gly Asp Trp Glu Leu Ala 180 Ile Ile Glu Giu 195 Gin Leu Ser Gin 210 <210> 125 <211> 1002 <212> DNA <213> Corynebact <220> <221> CDS <222> (101) (97 <223> RXA02205 <400> 125 gcccaaaccg agcctt caccacacta ctgag( PCT/IBOO/00922 135 140 Asp Val Ile Arg Ala Ser Asp Tyr Val Ile Thr Met 150 155 160 Val Cys Pro Met Tyr Pro Gly Lys His Tyr Leu Asp 165 170 175 Asp Pro Ser Asp Glu Gly Glu Asp Lys Ile Gin Giu 185 190 Ile Asp Giy Arg Ile Arg Giu Leu Trp Lys Ser Ile 200 205 Asn eriun giutamicum 9) ggata cccgcaaacc acttgaaccg accattcgct gtttcacgcc gtcat aaggtaqtac ggtagatcgg gtg aat gaa gag ata Val Asn Giu Giu Ile 1 Tca qca gca gat cct gcc gca act gaa aat att ggc kla Ala Ala Asp Pro Ala Ala Thr Giu Asn Ile Gly 15 ttt gtg ctc tcc atc gtt caa gqc ctc aca gag ttc le Val Leu Ser Ile Val Gin Gly Leu Thr Glu Phe 30 cc agc gga cac ctc cga atc atc tct gag ctg ttc er Ser Gly His Leu Arg Ile Ile Ser Giu Leu Phe 45 cc ggc gcg tcc ttt acc gcc gtg gtt cag ctt ggt la Gly Ala Ser Phe Thr Ala Val Val Gin Leu Gly 60 tg ctg gtg ttt ttt gcc aag gaa atc tgg caa atc al Leu Val Phe Phe Ala Lys Giu Ile Trp Gin Ile 75 80 tc gct ggc gta ttc aat aag gaa cgc cgc gga ttt he Ala Gly Val Phe Asn Lys Giu Arg Arg Gly Phe acc ctc Thr Leu tgg gta Trp Val ctg ccg Leu Pro tgg ggt Trp Gly acc gaa Thr Giu atc aca Ile Thr cta gcc Leu Ala caa acc Gin Thr atc agc Ile Ser gcc gat Ala Asp gcc qca Ala Ala ggt tgg Gly Trp a
I
t
S
9
A
g
V
t 115 163 211 259 307 355 403 WO 01/00804 WO 0100804PCT/IBOO/00922 gaa Glu a tc Ile atg Met tig Leu 150 at g Met cci Pro ggi Gly cci Pro cca Pro 230 ctg Leu t Phe gca tac Tyr ttig Leu igg Trp 135 gcc Ala aaa Lys ggC Gi y ctc Leu gca Ala 215 a gc Ser gitt Val1 gt g Val ggi cgc Arg ggi Gly 120 aic Ile gag Glu gat Asp gig Val aag Lys 200 gig Val1 icc Ser gcc Ala gca Ala ctg at g Met 105 gt q ValI act Tb r a ag Lys gcc Ala ict Ser 185 cgt Arg ct Leu gga Gly tc Phe aac Asn 265 ctc ggc Gly ttg Leu gca Al a atg Met aic Ile 170 cgc Arg ga a Glu ggc Gly caa Gin gta Val 250 cac His gtg Val t gg Trp qgc Gly icc Ser 9gC Gly 155 aic Ile icc Se r gi a Val1 icc Ser gci Ala 235 gt Val tcc Ser atg Met aag Lys gig Val1 140 aag Lys atg Met ggc Gly gcc Ala ggi Gly 220 gcc Ala 9gc tic Phe aic Ile ga c Asp 125 ci g Leu aag Lys ggi Giy Gly acc Thr 205 tig Leu icc S er tac Tyr agc Ser ati Ile 110 ct g Leu a tc Ile gaa Giu ct Leu acc Thr 190 aag Lys tac Tyr ggc Giy at i Ile tg Trp 270 gt Val1 aic Ile ci g Leu cgc Arg gca Ala 175 atc Ile ttc Phe icc Ser cia Leu icc Se r 255 ttt Phe gcc acc aii ccc Al a cgi Arg ttc Phe gac Asp 160 cag Gin i ct Ser icc Ser ci g Leu ca g Gin 240 att Ile gci Ala Tb r gag Glu icc Ser 145 iac Tyr i gi Cys gci Aila tic Phe cci Pro 225 ci c Leu gcg Aia gca Al a ggc Gly Ile gcg Ala 130 cig Leu g ac Asp cii Leu ggi Gly cig Leu 210 ga c Asp acc Thr i gg T rp tac Tyr Pro 115 cig Leu gig Val1 aaa Lys gcg Ala tig Leu 195 cig Leu gci Ala gig Val ctg Leu cgi Arg 275 gic gig Val Val cga aai Arg Asn tic aii Phe Ile ctg acc Leu Thr 165 ctg aic Leu Ile 180 tic ct Phe Leu gca aic Ala Ilie iii gcg Phe Ala ggi acc Gly Thr 245 aig aag Met Lys 260 ati cci Ile Pro 451 499 547 595 643 691 739 787 835 883 931 979 Ala Gly Leu Leu 280 atg ctg ctg cic gca ctg M1et Leu Leu Leu Ala Leu 285 aig cic aac cca M1et Leu Asn Pro 290 taaaattcct giacaicita aaa 1002 <210> 126 <211> 293 <212> PRT <213> Corynebacieriui glutamicum WO 01/00804 WO 0100804PCTIIBOO/00922 <400> 126 Val Asn Glu Giu Ile 1 5 Thr Giu Asn Ilie Giy Gly Leu Thr Giu Phe Ile Ser Giu Leu Phe Val Val Gin Leu Gly Giu Ile Trp Gin Ile Giu Arg Arg Gly Phe 100 Thr Ile Pro Val Val 115 Giu Ala Leu Arg Asn 130 Ser Leu Val Phe Ile 145 Tyr Asp Lys Leu Thr 165 Cys Leu Aia Leu Ile 180 Ala Gly Leu Phe Leu 195 Phe Leu Leu Ala Ile 210 Pro Asp Aia Phe Ala 225 Leu Thr Val Gly Thr 245 Ala Trp Leu Met Lys 260 Ala Tyr Arg Ile Pro 275 Giy Met Leu Asn Pro Thr Trp Leu Trp Thr 70 Ile Giu Ilie Met Leu 150 Met Pro Giy Pro Pro 230 Leu Phe Leu Val Pro Gly 55 Giu Th r Tyr Leu Trp 135 Ala Lys Gly Leu Al a 215 Se r Val1 Val1 Leu Gin Ile 40 Al a Al a Gly Arg Gly 120 Ilie Glu Asp Val1 Lys 200 Val1 Ser Al a Ala Al a Th r 25 Ser Asp Ala T rp Met 105 Val1 Thr Lys Al a Ser 185 Arg Leu Gly Phe As n 265 Ala Ile Ser Ala Val1 Phe Gi y Leu Ala Met Ile 170 Arg Giu Gly Gin Val 250 His Ala Val1 Ser Giy Leu Al a Trp Gly Ser Gly 155 Ile Se r Val1 Se r Ala 235 Val1 Ser Ala Leu Gi y Al a Val Gly Met Lys Val 140 Lys Met Gly Ala Gi y 220 Ala Gly Phe Asp Ser His Ser Phe Val Ile Asp 125 Leu Lys GI y Gly Thr 205 Leu Ser T yr Ser Pro Ile Leu Phe Phe Phe Ile 110 Leu Ilie Gi u Leu Th r 190 Lys Tyr Gly Ile Trp 270 Alia Gly Leu Leu Val Met Leu Leu Leu Ala Leu WO 01/00804 WOOI/0804PCT/IBOO/00922 290 <210> 127 <211> 975 <212> DNA <213> Corynebacterium giutamicun <220> <221> CDS <222> (952) <223> RXA00900 <400> 127 gtgcggtggc tgcgctggtc gctagtgtgg tgtgcgcgct ggcgccgtcg ataagcgtat tagtgatcgc acgcctggtg caggggcttg gcggcggtgc gtg cgt ggt att gcg Val Arg Gly Ile Ala cgc Arg ttt Phe ct C Leu t gg Trp cag Gin ggc Gly t tg Leu tac Tyr gta g cg Ala gca Al a at t Ilie gca Al a att Ile gga Gly gca Al a att Ilie ct 9 atc Ile ctg Leu ggt Gly ctt Leu aag Lys atg Met tat Tyr tcg Ser 120 ctg gtg Val1 Ctg Leu ggt Giy gca Ala gag Giu ctg Leu gta Val 105 geg Al a tat c ca Pro atg Met gtg Val1 ctg Leu tcg Ser tcc Se r ttc Phe tcg Ser tcc gac Asp at t Ile ctg Leu gtg Vali aag Lys 75 aac Asn aca Thr zcg Pro att *Ctt Leu att Sle gt C Val1 aat Asn 60 cca Pro tat Tyr ttg Leu ttc Phe att gaa.
Glu cag Gin ggg Gly 45 ttt Phe gt t Val gtc Val ggg Giy gtg Val1 125 tC cgc Arg gga Gly 30 cct Pro gcg Al a gaa Giu ttt Phe ct g Leu 110 ct g Leu gga gga 15 att.
Ile ttt Phe cag Gin gag Giu gtg Val1 95 tct Ser cag Gin gtg caa Gin gct Ala ggc Giy ctg Leu cgt Arg 80 ctg Leu ttt Phe aat Asn aat Asn aag Lys
CCC
Pro t gg Trp ctt Leu 65 acc Thr aag Lys ggg Gly ca a Gin gct Aia 145 gct Al a gtg Val cgg Arg 50 gtt Val1 gca Ala aat Asn gcg Al a atg Met 130 ttt gcg Al a gt a ValI 35 gga.
Gi y gct Aila gca Ala cct Pro atg Met 115 ggc Gly ggt ca c His 20 gct Ala att Ile t tg Leu gga.
GI y ca a Gin 100 ttc Phe att Ile t tg gcc Ala ccg Pro ttc Phe ctg Leu Ct t Leu ttt Phe t~c Ser ccg Pro att 163 211 259 307 355 403 451 499 547 Vai Leu Leu Tyr Ser Ile Ile Phe Gly Vai 135 140 Phe Gly Leu Ile gtg ggc gga atg gtc aat agg cga, ctt ctg cag cgg att cat cca. cac Val1 150 cgc Arg ttg Leu ctg Leu aca Thr gca Ala 230 ctg Leu act Thr WO 01/00804 Gly Gly Met atc atg caa Ile Met Gin ctg att gaa Leu Ile Glu 185 ctg ttt ctt Leu Phe Leu 200 gct ctg gga Ala Leu Gly 215 att ttg ggt Ile Leu Gly gtc gga tta Val Gly Leu gct tgt gca Ala Cys Ala Val1 act Thr 170 gt q Val1 atc Ile act Th r ttc Phe 9gC 250 t g ,e u PCT/IBOO/00922 Asn 155 gt g Val ctg Leu gtt Val gaa Gi u gtg ValI 235 t ct Ser ctg Leu Arg Arg ctq gcc Leu Ala ttt att Phe Ile tcc cat Ser His 205 gtg gtg Val Val 220 caa ttc Gin Phe gat aag Asp Lys gcg tgt Ala Cys Leu agt Ser aat Asn 190 at t Ile cga Arg acg Thr gct Ala ggg Giy 270 Leu ttt Phe 175 t gq Trp ccg Pro agc Ser atg Met ttg Leu 255 tgt Gin 160 act Thr ata Ile atg Met agg Arg ggt Gly 240 act Thr gcg Arg gtg Val1 ccg Pro gtt Val1 gcg Al a 225 gct Al a at g Met tac His tgt Cys ttc Phe 195 gct Ala t cg Se r gtg Val1 a tc Ile gca Cys Ala Tyr Leu Ala 275 265 aaa ggt att cca gaa atg aag tagctctagg tggcgtttta agg Lys Gly Ilie Pro Giu Met Lys 280 <210> 128 <211> 284 <212> PRT <213> Corynebacterium giutamicun <400> 128 Val Arg Gly Ilie Ala Arg Ala Ile Val Pro Asp Leu Glu Arg Gly Gin 1 5 10 Lys Ala Ala His Ala Phe Ala Leu Leu Met Ilie Ile Gin Gly Ile Ala 25 Pro Val Val Ala Pro Leu Ile Gly Giy Val Leu Val Gly Pro Phe Gly 40 Trp Arg Gly Ile Phe Trp Ala Leu Ala Leu Val Asn Phe Ala Gin Leu 55 Leu Val Ala Leu Leu Gin Ile Lys Giu Ser Lys Pro Val Glu Glu Arg 70 75 wo 01/00804 WO 0100804PCT/IBOO/00922 Thr Ala Ala Gly Leu Gly Gly Met Leu Ser Asn Tyr Val Phe Val Leu 90 Lys Gly Gin Ala 145 Arg Val Pro Val1 Al a 225 Al a Met Pro Gin 100 Met Phe 115 Gly Ile Gly Leu His Pro Cys Ala 180 Phe Leu 195 Ala Asn Ser Gly Val Ser Ile Ala 260 Leu Tyr Val1 Val1 150 Arg Leu Leu Th r Al a 230 Leu Thr Tyr Vai Phe 105 Ser Ala Ser 120 Leu Tyr Ser Gly Met Val Met Gin Thr 170 Ile Glu Val 185 Phe Leu Ile 200 Leu Gly Thr Leu Giy Phe Gly Leu Gly 250 Cys Ala Leu 265 Thr Pro Ile Asn 1.55 Val1 Leu Val1 Glu Val1 235 Ser Leu Tyr Leu Ala 275 Gly Arg Lys Gly Pro Glu Met Lys <210> 129 <211> 537 <212> DNA <213> Corynebacterium giutamicum <220> <221> CDS <222> (101)..(514) <223> RXN00901 <400> 129 ttttaagtat tggtgctatc ttccqgtgct gatggtacct gaatgaaaat ttctaattaa aaataccccc aaatcttcga tatagataca cgagacagtg atg cag aaa. aaa caa 115 Met Gin Lys Lys Gin 1 WO 01/00804 WO 0100804PCT/IBOO/00922 cag ctg agc acc gcc ctg att atg gga ttg gca tta ttg tca gcc Gin Leu Ser Thr Ala Leu Il~e Miet tcc gcg cta gcg act gat atg tat Ser Ala Leu Ala Thr Asp Met Tyr gaa gat ttg ggg aca act gca ccg Glu Asp Leu Gly Thr Thr Ala Pro ttt atg gct gga atg gcg att ggc Phe Met Ala Gly Met Ala Ile Gly gat caa ttg gga agg aaa ggc ctg Asp Gin Leu Gly Arg Lys Gly Leu ctg gtc qct agt gtg gtg tgc gcg Leu Val Ala Ser Val Val Cys Ala gtg atc qca cgc ctg gtg cag ggg Val Ilie Ala Arg Leu Val Gin Gly 105 ttg cgc gcg cga tcg tgc cag acc Leu Arg Ala Arg Ser Cys Gin Thr 120 125 acg cct ttg cac tgc tgatgattat Thr Pro Leu His Cys 135 <210> 130 <211> 138 <212> PRT <213> Corynebacterium glutamicur <400> 130 Met Gin Lys Lys Gin Gin Leu Ser 1 5 Leu Leu Ser Ala Ser Ser Ala Leu Met Pro Giy Ilie Ala Giu Asp Leu 40 Leu Thr Leu Ser Ser Phe Met Ala 55 Ile Giy Pro Leu Ser Asp Gin Leu 70 15 211 259 307 355 403 451 499 Leu Asn Ala Asp tcagggaatt gct Thr Ala Leu Ile Met Gly Leu Ala 10 Ala Thr Asp Met Tyr Leu Pro Al1a 25 Gly Thr Thr Ala Pro Met Val Gin Gly Met Ala Ile Gly Gin Leu Ile Gly Arg Lys Gly Leu Leu Val Ala 75 WO 01/00804 Gly Ala Val Ala Ala Leu Val Ala Ser Val Val Cys Ala Leu Ala Pro 90 Ser Ile Ser Val Leu Val Ile Ala Arg Leu Val Gin Giy Leu Gly Gly 100 105 110 Giy Ala Cys Val Val Leu Arg Ala Arg Ser Cys Gin Thr Leu Asn Ala 115 120 125 Asp Lys Arg Leu Arg Thr Pro Leu His Cys 130 135 <210> 131 <211> 501 <212> DNA <213> Corynebacterium glutamicum <220> <221> COS <222> (478) <223> FRXA00901 <400> 131 acctgaatga aaatttctaa ttaaaaatac ccccaaatct tcgatataga tacacgaga agtqatgcag aaaaaacaac agctgagcac cgccctgatt atg gga ttg gca tta Met Gly Leu Ala Leu PCTIBOO/00922 ic ttg Leu cct Pro act Thr ggt Gly gcg Ala ata Ilie gcg Ala tca Ser ggt Gly ct t Leu cct Pro gt g Val1 agc Se r t gc Cys agc Ser gcg Ala tcc Ser tcg Ser gcg Al a tta Leu gt a Val1 gcg Ala ga t Asp atg Met caa Gin gtc Val1 atc Ile cgc Arg gcg Ala ggg Gly gga Gly gga Gly agt Ser cg C Arg cga Arg act Thr aca Thr 30 atg Met agg Arg gt g Val1 ctg Leu tcg Ser ccg Pro gtg Val1 ttg Leu gt t Val1 geg Al a 99C Gly aac Asn WNO 01/00804 PCTIIBOO/00922 105 110 115 aaa agg ctg cgc acg cct ttg cac tgc tgatgattat tcagggaatt 498 Lys Arg Leu Arg Thr Pro Leu His Cys 120 125 gct 501 <210> 132 <211> 126 <212> PRT <213> Corynebacterium glutamicum <400> 132 Met Gly Leu Ala Leu Leu Ser Ala Ser Ser Ala Leu Ala Thr Asp Met 1 5 10 Tyr Leu Pro Ala Met Pro Gly Ile Ala Glu Asp Leu Gly Thr Thr Ala 25 Pro Met Val Gln Leu Thr Leu Ser Ser Phe Met Ala Gly Met Ala Ile 40 Gly Gin Leu Ile Ile Gly Pro Leu Ser Asp Gin Leu Gly Arg Lys Gly 55 Leu Leu Val Ala Gly Ala Val Ala Ala Leu Val Ala Ser Val Val Cys 70 75 Ala Leu Ala Pro Ser Ilie Ser Val Leu Val Ile Ala Arg Leu Val Gin 90 Gly Leu Gly Gly Gly Ala Cys Val Val Leu Arg Ala Arg Ser Cys Gin 100 105 110 Thr Leu Asn Ala Asp Lys Arg Leu Arg Thr Pro Leu His Cys 115 120 125 <210> 133 <211> 1299 <212> DNA <213> Corynebacterium giutamicum <22 0> <221> CDS <222> (101)..(1276) <223> RXA00289 <400> 133 cctccccata agttcactca agcaagttct cccgaacaga ttcacccgag aagtcgacag accccattaa acagcccgat tcaagaaagg cttcgcagcc atg agc acc acc acc 115 Met Ser Thr Thr Thr 1 WO 01/00804 WO 0100804PCT/IBOO/00922 gcg Ala gcg Ala aag Lys ttg Leu atg Met ct~g Leu tat Tyr gtg Val1 cac His ctg Leu 150 tgg Trp gc t Al a gaa Glu ct g Leu ccc Pro gca Ala ccg Pro atg Met t ig Leu gca Al a gga Gly ttt Phe act Th r 135 gt c Val1 cgt Arg gta Val tca Ser gtC Val 215 ga a Glu ttt Phe atg Met act Thr t gq Trp t tt Phe atg Met tgg Trp 120 ggt Gly gtt ValI cct Pro ctc Leu gag Glu 200 att Ile gca Al a gtt ValI gcc Al a qtg Val1 gtt Val1 ttg Leu cta Leu 105 gca Ala cgt Arg ggt Gly gcc Ala att Ile 185 tcc Ser ttc Phe cgg ttt cct gtc gtc cct ttg acc gcc atg agt ttc Arg tat T yr agc Ser tat Tyr t ct Se r gCC Ala gcc Ala ctt Leu gca Al a tct Ser acc Thr 170 cca Pro aaa Lys ct t Leu Phe Pro Val Val Pro Leu Thr Ala Met Ser Phe 15 gtc Val1 ga t Asp gcg Ala cga Arg 75 acg Thr atc Ile gt t Val1 gta Val1 ccg Pro 155 tgg Trp acc Thr gaa Glu ct C Leu acg Thr ctt Leu act Thr 60 tt Phe ggC Gl y qgC Gly qgg Gly 9gC Gly 140 ctg Leu att Ile gt t Val1 a ag Lys ctt Leu 220 ttc Phe gga Gl y 45 gt c Val1 aac Asn att Ile cgc Arg cca Pro 125 gt t Val gca Al a ct t Leu cca Pro aaa Lys 205 gcc Al a gag Glu 30 gt g ValI gt t Val1 aag Lys gtt Val1 act Thr 110 atg Met gt g Val1 aca Thr gg t Gly tca Ser 190 tcc Ser gt C Val1 atg Met t ca Se r gcc Ala cgc Arg gt t Val1 95 atc I le gca Al a t cg Ser tgg Trp qcg Ala 175 ctg Leu ctt Leu acc Thr ttt Phe qaa Glu gtg Val a ca Thr cag Gin gca Ala gcg Al a att Ile atc Ile 160 ctg Leu cca Pro cca Pro ggt Gly gca Ala t CC Ser gt g Val1 gt t Val1 gca Ala gca Ala cgt Arg gga Gly 145 ggt Gly acc Thr cca Pro tgg Trp gtt Val gtt ggc Val Gly agc atc Ser Ile acg atc Thr Ile ttc ctg Phe Leu ctg acc Leu Thr ttg act Leu Thr 115 atg tcc Met Ser 130 tca acc Ser Thr gaa ctc Giu Leu att gcg Ile Ala ctt cca Leu Pro 195 ggt ctc Gly Leu 210 ttt gct Phe Ala ct c Leu ggc Gi y cct Pro att Ile gt t Val1 100 cac His cc a Pro atg Met atc Ile gcc Ala 180 gac Asp att.
Ile gcc Al a acc tac ctt ggc ctc atc atc gct gaa aca gca ggg gac agc ttC gtg WO 01/00804 WO 0100804PCT/IBOO/00922 Thr Tyr Leu Gly Leu Ile Ile Ala Glu Thr Ala Gly Asp Ser Phe Val 230 235 240 245 99C Gi y acc Thr act Th r 280 gag Glu ggt Gly cat His act Thr gtg Val 360 tca ttc gcc Phe Ala 250 act gtg Thr Val ttt gtC Phe Val aca cta Thr Leu gca tac Ala Tyr 315 ggt cgc Gly Arg 330 caa gtg Gin Val gcc gat Ala Asp gct tcc tt c Phe ga t Asp att Ile gcc Al a 300 ggc Gly gac Asp ggt Gly tgg Trp acg gca Ala cgc Arg 270 gca Ala gta Val ctc Le u cca Pro gcg Ala 350 gct Ala gcc gga Gly ctg Leu ctc Leu atc Ile acc Thr 320 act Thr ggc Gly act Thr gcg Ala gtg Val 260 gtt Val gca Ala qtC Val1 acc Thr att Ile 340 ggc Gly at g Met cgc Arg 883 931 979 1027 1075 1123 1171 1219 1267 1299 Gly Leu Ser Leu Ala Ser Thr Leu Ala Leu 375 380 cta ctg aag tagcagccca aattcagccc act Leu Leu Lys 390 <210> 134 <211> 392 <212> PRT <213> Corynebacterium glutamicwn <400> 134 Met Ser Thr Thr Thr Ala Pro Glu Ala Arg Phe Pro Val Val Pro Leu 1 5 10 Thr Ala Met Ser Phe Ala Ala Phe Val Tyr Val Thr Phe Giu Met Phe 25 Ala Val Gly Leu Ile Lys Pro Met Ala Ser Asp Leu Gly Val Ser Glu WO 01/00804 40 Ser Ser Ile Gly Leu Leu Met Thr Val Tyr Ala Thr Val Val Ala Val 55 Val Thr Ile Pro Ala Met Leu Trp Val Ser Arg Phe Asn Lys Arg Thr 70 75 Val Phe Leu Ile Thr Leu Ala Phe Leu Ala Thr Gly Ile Val Val Gin 90 Ala Leu Thr Val Asn Tyr Gly Met Leu Ala Ile Gly Axg Thr Ile Ala 100 105 110 Ala Leu Thr His Gly Val Phe Trp Ala Leu Val Gly Pro Met Ala Ala 115 120 125 Arg Met Ser Pro Gly His Thr Giy Arg Ala Val Gly Vai Val Ser Ile 130 135 140 Gly Ser Thr Met Ala Leu Val Val Gly Ser Pro Leu Aia Thr Trp Ile 145 150 155 160 Gly Giu Leu Ile Gly Trp Arg Pro Ala Thr Trp Ile Leu Giy Ala Leu 165 -170 175 Thr Ilie Ala Ala Val Ala Val Leu Ile Pro Thr Val Pro Ser Leu Pro 180 185 190 Pro Leu Pro Asp Thr Giu Ser Giu Ser Lys Giu Lys Lys Ser Leu Pro 195 200 205 Trp Gly Leu Ile Ser Leu Val Ile Phe Leu Leu Leu Ala Val Thr Gly 210 215 220 Val Phe Ala Ala Tyr Thr Tyr Leu Gly Leu Ile Ile Ala Giu Thr Ala 225 230 235 240 Gly Asp Ser Phe Val Ser Ile Gly Leu Phe Ala Phe Gly Ala Leu Gly 245 250 255 Leu Ilie Gly Val Thr Val Ala Thr Arg Thr Vai Asp Gin Arg Met Leu 260 265 270 Arg Gly Ser Val His Thr Thr Thr Leu Phe Val Ile Ala Ala Ile Leu 275 280 285 Gly Gin Ile Ala Phe Gly Leu Giu Gly Thr Leu Ala Val Val Ala Ile 290 295 300 Phe Leu Ala Val Thr Val Phe Gly Gly Ala Tyr Gly Ala Leu Pro Thr 305 310 315 320 Leu Gly Thr Thr Ile Phe Leu His Ala Gly Arq Asp His Pro Asp Thr 325 330 335 Ala Ser Ser Ile Tyr Val Val Thr Tyr Gin Val Gly Ile Ala Ser Gly PCTIBOOIOO922 WO 01/00804 340 345 350 Ala Ala Leu Gly Ala Met Ala Val Asp Ala Asp 355 360 Leu Trp Ile Met Ala Gly Leu Ser Leu Ala Ser 37 0 375 Leu Trp Ser Arg Pro Leu Leu Lys 385 390 <210> 135 <211> 420 <212> DNA <213> Corynebacterium glutamicum <220> <221> COS <222> (397) <223> RXN01984 <400> 135 aggaaatgtc tcacgtcaca accttttgaa aggtggctaa caatagtgcc ggtgagggag ctgtccgata ttgtgcttac Trp Val Ala Gly inr 365 Thr Leu Ala Leo Ala 380 aaa aat cct gtc aag gtt g Lys Asn Pro Val Lys Val V ggg cat atc ggc gga cat a Gly His Ile Gly Gly His I gaa att tcc gag gtt cgt c Glu Ile Ser Glu Val Arg A ggt ggc ttc gcc atc ggt g Gly Gly Phe Ala Ile Gly V, agc gcg atc gcc tcc gac ti Ser Ala Ile Ala Ser Asp P1 75 atc atc acc atc tac gcc cl Ile Ile Thr Ile Tyr Ala Li tgatcacagc gtttaccggc aaa <210> 136 t cg Ser cgC Arg 30 atc Ile ga a Giu atc Ile t gg T rp cag Gin 15 cgC Arg gt C Val1 ttt Phe t cc Ser ttg Leu gtacgcacat ttgttgtc atg cac gaa tct gga Met His Giu Ser Gly 1 cca caa gga cgc ggt Pro Gin Gly Arg Gly att cct agg caa acg Ile Pro Arg Gin Thr act gcc ctc gca ctc Thr Ala Leo Ala Leo tcc atg ggt ctg ctc Ser Met Giy Leu Leo gac caa gcc gga cac Asp Gin Ala Gly His gtg ccc cgc Vai Pro Arg PCT/IBOO/00922 tg 115 163 211 259 307 355 397 WO 01/00804 <211> 99 <212> PRT <213> Corynebacteriwn giutamicum <400> 136 Met His Giu Ser Gly Lys Asn ProI 1 Pro Gin Gly Arg Gly Gly His Ile( Ile Pro Arg Gin Thr Glu Ile Ser Thr Ala Leu Ala Leu Giy Gly Phe 1 Ser Met Gly Leu Leu Ser Ala Ile Asp Gin Ala Gly His Ile Ile Thr 1 Val Pro Arg PCT/IBOO/00922 <210> 137 <211> 379 <212> DNA <213> Corynebacteriun giutamicum <22 0> <221> CDS <222> (101)..(379) <223> FRXA01984 <400> 137 aggaaatgtc tcacgtcaca accttttgaa aggtggctaa caatagtgcc ggtgagggag ctgtccgata ttgtgcttac cct gtc Pro Val atc ggc Ile Gly tcc gag Ser Giu ttc gcc gtc gac Val Asp atc aaa Ile Lys cga tat Arg Tyr 45 gtg acg cag gca Gin Ala cgc ccg Arg Pro gtc atg Val Met ttt gtc gtacgcacat ttgttgtctg atg cac gaa tct gga Met His Giu Ser Gly 1 cca caa gga cgC ggt Pro Gin Gly Arg Gly att cct agg caa acg Ile Pro Arg Gin Thr act gcc ctc qca ctc Thr Ala Leu Ala Leu tcc atg ggt ctg ctc WO 01/00804 Giy Gly Phe Ala agc gcg atc gcc Ser Ala Ile Ala atc atc acc atc Ile Ile Thr Ile PCT/IBOO/00922 Thr Giu Phe Val Ser Met Gly Leu Leu gag atc tcc gaa gac caa gcc gga cac Glu Ile Ser Giu Asp Gin Ala Gly His 80 gcg Ala <210> 138 <211> 93 <212> PRT <213> Corynebacterium giutamicum <400> 138 Met His Giu Ser Gly Lys Asn Pro Val 1 5 Pro Gin Gly Arg Gly Gly His Ile Gly 25 Ile Pro Axg Gin Thr Giu Ile Ser Giu Thr Ala Leu Ala Leu Gly Giy Phe Ala Ser Met Gly Leu Leu Ser Ala Ile Al~a 70 Asp Gin Ala Gly His Ile Ile Thr Ile Ser Gin Ala Arg Arg Pro Ile Val Met Giu Phe Vai Ile Ser Giu <210> 139 <211> 735 <212> DNA <213> Corynebacteriun giutamicun <220> <221> CDS <222> (101)..(712) <223> RXA00109 <400> 139 aagtgqggga agatttcgac aactaaccgg gcgcaaagat gaaactaatg cgtccgacca cggcgaaaag gaagtttcgc ccatctatga gaggttgaat gtg gct tca gag aag 115 Val Ala Ser Glu Lys 1 aat cta aaa ttg cgt acc ttg gcg gca gct gct ggg gtg ttg ggc gtt 163 Asn Leu Lys Leu Arg Thr Leu Ala Ala Ala Ala Gly Val Leu Gly Val 15 WO 01/00804 ggc gcg atg tcg atg ctc gtg qct Gly Ala Met Ser Met Leu Val Ala PCTIBOO/00922 ccg cag qct gct gcc cat gat gtg 211 Pro Gin Ala Ala Ala His Asp Val 30 gtg Val1 gag Glu a ca Thr act Thr gtg Val1 tct Se r tct Ser gca Ala 150 act Thr agc Ser gtg Val1 acc Thr gtt Val1 cc t Pro cag Gin gat Asp gct Ala 135 gca Al a gct A~la atc Ile gat Asp att Ile gca Al a ca g Gin acg Thr ggt C-ly 120 ga a Glu acc Thr gat Asp gtg Val tct Ser gag Glu ttg Leu ctt Leu gga Gly 105 ca c His acg Thr act Thr gaa Glu gcg Ala aat Asn tt g Leu agc Ser gag Glu gct Al a gct Ala aca Thr gac Asp act Thr 170 gtg lal cct Pro gag Glu aat Asn 75 ggg Gly ggt Gly act Thr aca Thr acc Thr 155 tct Ser gaa Glu ttt Phe 60 gcg Al a cag Gin aac Asn aaa Lys gag Glu 140 t ca Ser gga Gly aat As n 45 tcc Se r gat Asp cac His tac Tyr ggt GI y 125 aca Thr gag Glu att Ile 99C Glj ggt Gly t cc Sex ttg Leu att Ile 110 t ca Ser a ca Thr acc Thr cct Pro agt gtc Ser Val att oct Ile Pro gga gag Gly Glu 80 agc tat Ser Tyr 95 ttg ggt Leu Gly ato tct Ile Ser gca gag Ala Giu acc gaa Thr Giu 160 gcg cog Ala Pro 175 agt gc Ser Ala gtt Val1 cag Gin gtg ValI gaa Glu ttc Phe ttt Phe acg Th r 145 gca Ala t gg Trp atc ga t Asp ga t Asp tta Leu gtg Vai ca g Gin gag GI u 130 aca Thr gag Giu aat Asn gt C gag Glu ctg Leu act Th r ca Pro atc Ile 115 gt g ValI act Thr a ca Thr t gg Trp, atg ttc ccg Phe Pro ttc aca Phe Thr tot gga Ser Gly tot gat Ser Asp 100 act tct Thr Ser aca ggc Thr Gly gag tca Glu Ser act gaa Thr Giu 165 gtt ttg Val Leu 180 atg att Met Ile 259 307 355 403 451 499 547 595 643 691 Leu Vai Val Ala Ile Val Met 185 gca aag aat cgt aac cag aaa taagagggtt tattcaccat gaa Ala Lys Asn Arg 200 Asn Gin Lys <210> 140 <211> 204 <212> PRT <213> Corynebacterium giutamicum <400> 140 Val Ala Ser Glu Lys Asn Leu Lys Leu Arg Thr Leu Ala Ala Ala Ala WO 01/00804 WO 0100804PCTfIBOO/00922 1 Gly Val Leu Gly Val Gly Ala Met Ser Ala Ala His Asp Val Val Val Val1 Gin Val1 Glu Phe Phe Th r 145 Al a Trp Asp Giu Asp Leu Leu Thr Val Pro Gin Ilie 115 Glu Val 130 Thr Thr Giu Thr Asn Trp Phe Phe Ser Se r 100 Thr Thr Glu Th r Val1 Pro Thr Giy Asp Ser Gly Ser Gi u 165 Leu Glu Thr 70 Th r Val1 Ser Ser Al a 150 Thr Ser Thr 55 Val1 Pro Gin Asp Al a 135 Ala Ala Asp 40 Ile Ala Gin Thr Gi y 120 Glu Thr Asp Se r Glu Leu Leu Gly 105 His Thr Thr Glu 10 Met Asn Leu Ser Gl u Ala Ala Thr Asp Thr 170 Pro Glu Asn Gly Gly Thr Thr Thr 155 S er Gin Ala Leu Val Ala Pro Giu Phe Ala Gin As n Lys Giu 140 Ser Giy Val1 Asn Gly Ser Gly Asp Ser His Leu Tyr Ile 110 Gly Ser 125 Thr Thr Giu Thr Ile Pro Val Ala 190 Ile Vai Ala Val Leu 185 180 Ile Val Met 195 Met Ilie Ala Lys As n 200 Arg Asn Gin Lys <210> 141 <211> 735 <212> DNA <213> Corynebacterium giutamicum <220> <221> CDS <222> (712) <223> RXA00109 <400> 141 aagtggggga agatttcgac aactaaccgg gcgcaaagat gaaactaatg cqtccgacca cggcgaaaag gaagtttcgc ccatctatga gaggttgaat gtg gct tca gag aag 115 Val Ala Ser Giu Lys 1 aat cta aaa ttg cgt acc ttg gcg gca gct gct ggg qtg ttg ggc gtt 163 wo 01/00804 WO 010080PCT/IBOO/00922 Asn Leu Lys Let' 9gc Gly gtg Val gag Glu aca Thr act Thr gt g Val tct Se r tct Se r gca Ala 150 act Thr agc Ser gca Ala gcg Ala gtg Val acc Thr gt t Val1 cct Pro cag Gin ga t Asp gct Ala 135 gca Ala gct Al a atc Ile atg Met ga t Asp at t Ile gca Ala cag Gln acg Thr ggt Gly 120 gaa Glu acc Thr ga t Asp gtg Val1 t cg Se r tct Se r gag Git' ttg Leu ct t Leu gga Gly 105 cac His acg Thr act Thr gaa Glu gcg Ala 185 Arg atg Met aat Asn t tg Leu a gc Ser gag Giu gct Al a gct Al a aca Thr gac Asp act Thr 170 gtg Val Thr Leu Ala Ala Ala Ala Giy Val Leu Gly Val ctc Leu cct Pro gag Glu aa t As n 75 ggg Gly ggt Gl y act Thr aca Thr acc Thr 155 t ct Ser ctt Leu gtg gct ccg Val Ala Pro 30 gaa aat ggc Glu Asn Gly 45 ttt tcc ggt Phe Ser Gly 60 gcg gat tcc Ala Asp Ser cag cac ttg Gin His Leu aac tac att Asn Tyr Ile 110 aaa ggt tca Lys Gly Ser 125 gag aca aca Giu Thr Thr 140 tca gag ac Ser Glu Thr gga att cct Gly Ile Pro gtt gtt gca Val Val Ala 190 cag Gin agt Ser at t Ile gga Gi y agc Ser 95 t tg Leu atc Ile gca Ala acc Thr gcg Al a 175 agt gct Ala gtC Val1 cct Pro gag Giu 60 tat Tyr ggt Gly tct Ser gag Giu gaa Glu 160 ccg Pro gcc gct Ala gtt Val1 cag Gin gtg Val gaa Giu ttc Phe ttt Phe acg Thr 145 gca Ala t gg Trp atc: gcc Ala gat Asp ga t Asp tta Leu gt g Val1 ca g Gin gag Glu 130 aca Thr gag Glu aat Asn gt c cat His gag Glu ct g Leu act Thr cca Pro atc Ile 115 gtg Val act Thr a ca Thr t gg Trp atg Met 195 ga t Asp ttC Phe ttc Phe tct Ser t ct Ser 100 act Thr a ca Thr gag Glu act Thr gtt Vai 180 atg Met gtg Val1 cog Pro aca Thr gga Gly gat Asp t Ct Ser ggc Gly t ca Ser ga a Glu 165 ttg Let' at t Ile Ser Ala Ile Val aag aat cgt aac cag aaa taagagggtt tattcaccat gaa Lys Asn Arg Asn Gin Lys <210> 142 <211> 204 <212> PRT <213> Corynebacterium glutainicum WO 01/00804 <400> 142 Val Ala Ser Glu Lys 1 5 Gly Val Leu Gly Val Ala Ala His Asp Val Val Asp Glu Phe Pro Gin Asp Leu Phe Thr Val Leu Thr Ser Gly Giu Val Pro Ser Asp 100 Phe Gin Ilie Thr Ser 115 Phe Glu Val Thr Gly 130 Thr Thr Thr Glu Ser 145 Ala Glu Thr Thr Giu 165 Trp Asn Trp Val Leu 180 PCT/[BOO/00922 Asn Leu Lys Leu Ala Val Thr Val1 Pro Gin Asp Ala 135 Ala Ala Ile Met Ser 25 Asp Ser 40 Ilie Glu Ala Leu Gin Leu Thr Gly 105 Giy His 120 Glu Thr Thr Thr Asp Glu Val Ala 185 Arg 10 Met Asn Leu Ser Glu Ala Al a Thr Asp Thr 170 Val1 Thr Leu Ala Ala Ala Ala Leu Pro Glu Asn Gly Gly Thr Thr Thr 155 Ser Leu Ala Pro Asn Gly Ser Gly Asp Ser His Leu Tyr Ile 110 Gly Ser 125 Thr Thr Glu Thr Ile Pro Val Ala 190 Ile Val Met 195 Met Ile Ala Lys Asri 200 Arg Asn Gin Lys <210> 143 <211> 864 <212> DNA <213> Corynebacteriun giutamicwn <220> <221> COS <222> (101)..(841) <223> RxA00996 <400> 143 atcttaagcc ttttgtccaa ggctctgagt tcttaqtggc ggtatttacc aaqaagtaac acctctatct tgcacctgat ctggcgtaga ctcataagtt atg agc acc gta acg 115 Met Ser Thr Val Thr 1 WO 01/00804 gca Al a ege Arg ace Thr act Thr gag Glu ggc Gly ga a Glu cgc Arg caa Gin ct t Leu 150 cca Pro t tc Phe gig Val1 ggt Gly gtg Val1 aag Lys gga Gly t ig Leu gig Val1 tat Tyr aa c As n ace Th r cgc Arg 135 gga Gly ace Thr ac Thr ttg Leu cag Gin aaa Lys aag Lys atg Met ttt Phe gte Val1 etc Leu ceg Pro 120 caa Gin t gt Cys gig Val1 ace Thr gag Giu 200 gte Val1 aca Thr ate Ilie ege Arg gai Asp ace Thr aag Lys 105 ga a Gi u gi a Val1 geg Ala ggt Gly aic Ile gaa Giu2 aac Asn aaa Lys acg Thr 9gg Al a cag Gin caa Gin tat Tyr aag Lys tea Ser ctt Leu tig Leu 170 gca Al a gcc Pd a ggC Gly a cg Thr gga Gly at Ile ccc Pro 75 aac Asn tc Phe att Ile a ca Thr att.
Ilie 155 ga t Asp aaa Lys gcg Ala cia Leu ate Ile tt g Leu gig Val1 60 gca Al a gee Ala ggg Gly cig Leu cia Leu 140 gee Al a ccc Pro gca Ala Cgg Arg aaa Lys tig Leu ctg Leu 45 gga Gly g gi Giy age Ser get Ala gag Giu 125 ict Ser tea Ser att Ile ggt Gly t gc Cys 205 gt Val1 cat His 30 ggg Gly gig Val1 get.
Ala gia Val1 ct g Leu 110 gte ValI ggt Gly eca Pro ace Thr get Ala 190 ga e Asp icc ata Ser Ile 15 gat etc Asp Leu cca teg Pro Ser eaa aac Gin Asn gee ict Ala Ser tat cac Tyr His 95 get aaa Ala Lys tia gac Leu Asp ggg cag Gly Gin gaa etc Glu Leu 160 egg caa Arg Gin 175 gga gig Giy Val aac etc Asn Leu teg tee Ser Ser gat ttc Asp Phe gge age Gly Ser te gac Phe Asp cig ege Leu Arg gat ctg Asp Leu gga ace Gly Thr ate gea Ile Ala 130 ege gge Arg Gly 145 tig gtg Leu Val gca ctg Ala Leu git ate Val Ile att. tig Ile Leu 210 ggt Gly ace Th r gge GI y Gly ggg Gly tcg Ser tee Ser 115 ga t Asp cga Arg a ig Met tgg Trp tee Ser 195 tig Leu ttt Phe gi a Val1 aag Lys ace Thr aaa Lys gtg ValI 100 act Thr ctt Leu gte Val gat Asp ga a Glu 180 agt Ser egi Arg PCT/IBOO/00922 163 211 259 307 355 403 451 499 547 595 643 691 739 787 egg ate ate tgg agg gga aca ccc aca ege ett. eta gaa gat aca Asp Thr Arg Ile Ile Trp Arg 215 Thr Pro Thr Arg Leu Leu Glu 225 WO 01/00804 PCT/IBOO/00922 ggc aaa age tca tac gaa gat gct ttc ttg get gcc att gac ggg gta 835 Gly Lys Ser Ser Tyr Glu Asp Ala Phe Leu Ala Ala Ile Asp Gly Val 230 235 240 245 agg tea tgaaecctca ctatctgett gee 864 Arg Ser <210> 144 <211> 247 <212> PRT <213> Corynebacterium glutamicum <400> 144 Met Ser Thr Val Thr Ala Val Gin Val Asn Gly Leu Lys Val Ser Ile 1 Ser Asp Gly Phe Leu Asp Gi y Ile Arg 145 Leu Ala Val1 Ser Gly Phe Thr Ser Gly Asp Gly Arg Gly Leu Ser Thr Ser 115 Ala Asp 130 Gly Arg Val Met Leu Trp Ile Ser 195 5 Ser GI u Thr Leu Ilie Ile Pro Al a Se r Glu 165 Giu His Arg Thr Thr Giu 710 Gly Glu Arg Gin Leu 150 Pro Phe Val1 Lys Giy Leu 55 ValI Tyr As n Thr Arg 135 Gly Thr Thr Leu Lys Lys 40 Met Phe Val1 Leu Pro 120 Gin Cys Val Thr Glu 200 Lys Thr Ala Gin Gin 90 Tyr Lys Ser Leu Leu 170 Ala Ala Ile Leu Leu Leu Val Gly Ala Gly Ala Ser Gly Ala Leu Gbu 125 Leu Ser 140 Ala Ser Pro Ile Ala Gly Arg Cys 205 Asp Pro Gin Ala Tyr Al a Leu Giy Giu Arg 175 Gly Asn Leu Ser Asn Ser His Lys Asp Gin Leu 160 Gin Val Leu Ile Leu 210 Leu Arg Asp Giy Axg 215 Ile Ile Trp Arg Gly Thr Pro Thr Arg 220 WO 01/00804 Leu Leu Glu Asp Thr Gly Lys Ser Ser Tyr Giu Asp Ala Phe Leu Ala 225 230 235 240 Ala Ile Asp Gly Val Arg Ser PCT/IBOO/00922 <210> 145 <211> 2463 <212> DNA <213> Corynebacterium qlutamicun <220> <221> CDS <222> (101).-(2440) <223> RXN00829 <400> 145 tgttttagcc atggacccca tactagggag agttttgttt tggtgctaga aaaggttcac caagcgcgaa caggcctatg caaacggtac gatatgacac atg caa aaa gct gat Met Gin Lys Ala tcc cat gat tgg att tcg gtc cac Ser His Asp Trp Ilie Ser Val His aat gtg tcg Asn Val Ser gtg tcg gga Val Ser Gly gaa tca cgc Glu Ser Arg ttc atg ccg Phe Met Pro acc acg gcg Thr Thr Ala tct acg gtg Ser Thr Val ttt tcc cga Phe Ser Arg 120 gtg Val1 tct Ser cgg Arg tcg Se r at c Ile ggt Gly 105 atc: Ile cgc atc cct aaa Arg 9gC Gly ttg Leu atg Met atc Ile a cc Thr gcg Ala Ile aag Lys atc Ile gca Ala 75 gtc Val1 qca Al a ga a Glu Pro Lys tcC tcg Ser Ser 45 aac gaa Asn Ciii 60 agg ccc Arg Pro gat cag Asp Gin act gat Thr Asp gg t Gly agg Arq 30 ctg Leu acc Th r ga t Asp gag Giu gcC Al a 110 gcg Al a 15 cgt Arg gtg Val1 tat Tyr gtt Val cag Gin 95 acc Thr aat Asn ctc Leu ttc Phe agc Ser gac: Asp 80 atg Met gcg Ala 1 ga a Gl u acc Thr ggc Giy act Thr cat His ggC Gly atg Met aac: Asn gtg Val1 aca Thr ttt Phe ttg Leu gca Ala ttg Leu aac Asn ttc Phe att Ile gt g Val1 gaa Giu aac Asn cgc Arg ctc Leu a cg Thr gct Ala ca a Gin Gly cca Pro 100 att Ile Asp aaa Lys ggt Gi y gcg Ala ggt Gly atc Ile cgg Arg ttg Leu 115 163 211 259 307 355 403 451 115 cct aac gcg ggt ggc ccg gga gct tat tcc Pro Asn Ala Gly Gly.Pro Ala Tyr Ser 125 ttc aac gtc ccc tct gtt tcc gca tcc ggc gcc: atc: acg gtg gaa aag WO 01/00804 WO 0100804PCT/1BOO/00922 Phe ggc Gly 150 atg Met aaa Lys atc Ile tog Ser gaa Glu 230 ggc Gly atg Met gt g Val oga Arg gct Ala 310 a og Thr aco Thr As n 135 gga Gly tgc Cys gag Glu ccc Pro ggc Gly 215 cgo Arg a to Ilie ttg Leu ga t Asp tta Leu 295 gag Glu gtg Val ctg Leu Val aac As n cc a Pro ctt Leu ggt Gly 200 ctt Leu cac His aac Asn tot Se r oga Arg 280 gog Ala t tg Leu gaa Glu ga t Asp Pro Ser Val Ser Ala Ser Gly Ala Ile Thr Val Glu Lys aoo Thr gog Ala tto Phe 185 tao Tyr ttt Phe aa c Asn atg Met aag Lys 265 gog Al a ooa Pro tgo Cys goo Ala aac Asn 345 aag Lys t go Cys 170 gao Asp aoo Th r ga t Asp ttc Phe aoo Thr 250 gat Asp gt t Val cat His gog Al a 000 Pro 330 tto Phe t
S
140 ogg gag Arg Glu 155 gag ggo Giu Gly goo too Ala Ser ooa ggt Pro Gly got gcc Ala Ala 220 ctt tat Leu Tyr 235 tat gag Tyr Glu cgo gaa Drg Giu 300 ttc rhr Phe ;cc ttg kla Leu 300 Itg gag 4et Giu 315 cog gtt er Val rtg gag ral Glu 145 aaa Lys atg Met ot c Leu gga Gly 205 aag Lys ott Leu ggt Gly ggo Gly att Ile 285 gag Glu gto ValI got Ala ato Ile got Ala ggo Gly too Ser 190 t gg T rp cog Pro gag Giu ctt Leu atg Met 270 cot Pro too Ser ogt Arg 000 Pro gt Gly 350 aoo Thr agg Arg 175 oto Leu agt Ser att Ile 000 Pro atc Ile 255 oag Gin tgo Cys aag Lys gat Asp ot g Leu 335 ttg Leu tto Phe 160 gc Ala aao Asn tat T yr aag Lys acc Thr 240 coo Pro aag Lys Oct Pro ato Ile ttg Leu 320 ctc Leu ggc Gly aaa Lys t ca Ser gao Asp ogy Arg ga t Asp 225 aag Lys ogo Arg oat His gcg Aila aat Asn 305 goo Ala aoo Thr tat Tyr ogo aog Arg Thr gao ato Asp Ile ggo gco Gly Ala 195 atg tat Met Tyr 210 tto acc Phe Thr atg aag Met Lys att cay Ile Gin att ogt Ile Arg 275 tgt ggt Cys Gly 290 ggo aaa Gly Lys aag tgg Lys Trp goa otg Ala Leu ato oaa Ile Gin 355 ggt Gly gao Asp 180 otg Leu toa Se r gag Glu ato Ile aaa Lys 260 gog Al a gga Gly aac Asn ato Ile act Thr 340 Ot 0 Le u ggo Gi y 165 ot 0 Le u aco Th r ga a Gi u gaa Glu got Al a 245 too Ser ttc Phe act Thr ato Ile aaa Lys 325 ga a Glu ga t Asp 595 643 691 739 787 835 8B3 931 979 1027 1075 1123 1171 1219 ogc coo got Arg Pro Ala ggo acg ttg tot ggt Gly Thr Leu Ser Gly ggt Gly gag goa cag ogo aoo aag atg Glu Ala Gin Arg Thr Lys Met wo 01/00804 WO 0100804PCT/IBOO/00922 at c Ile gaa Glu 390 ttg Leu cac His cca Pro ga c Asp cqg Arg 470 atc Ile ccc; Pro t cc S er gat Asp aca Thr 550 cgtc cgc Arc; 375 ccc Pro ctg Leu aag Lys cgct Gly aa g Lys 455 qcg Ala ccc Arg ct C Leu tcg Se r caa Gin 535 9gC Gly aaa cat His a cc Thr ct c Leu ccc; Pro gca Ala 440 ctt Leu t ca Ser ggc; Gly ggC Gly ttc; Leu 520 acc Thr atg Met ccc; ttg Leu cgcc Ala ga t Asp gaa Glu 425 ggc Gly aaa Lys tt g Leu gcc Aia gt g Val1 505 at t Ile cgca Al a ctg Leu gcg 9Ccc Gly cggt Gi y ct t Leu 410 acc Thr gcg Al a ga c Asp aag Lys gat Asp 490 ttc Phe cat His ate Ile gat Asp ctg tct Sei tt Let 395 cgc Arg atc Ile cgt Gl y agc Ser gaa Giu 475 cga Arc; acg Thr gag di u cac His tcc; Ser 555 ttC gca r Ala 380 cac His g cat Asp ccc *Ala gga Gly gac Asp 460 tcc Ser aat Asn gec; Al a att Ile ggt Gly 540 att Ile tcC Ser ttg Leu cgcc Al a aaa Lys att Ile Gly 445 acc Thr qt g Val1 aat As n att Ile ccc; Pro 525 tct Ser cgc A.rg ~ccc Pro pact IThr tac Tyr cgca Ala 430 gaa Glu Val1 cqt Arc; tic; Leu t cc Ser 510 cgt Arc; aat Asn aag Lys aat Asn gac Asp gac Asp aat Asn 415 *gat *Asp att Ile act Thr gcg Al a aac As n 495 di y gat Asp cgt Arc; gct Ala tct Ser 575 cgtc Val1 at t Ile 400 ac Thr cat His Arc; Gly ccc; Pro 480 aat Asri gt t ValI cgac; Gi u tcc Ser ttt Ph e 560 ga a Gi u acc Thr 385 cgaa Giu cgtt Val gig Val1 ttt Phe ct c Leu 465 cat His cgtg ValI cgca Ala t cc Ser aa t Asn 545 cc Ala 9gc Gly tat Tyr ccc Arc; tta Leu gig Val1 gag Gl u 450 cat His 9Ccc Gly gat Asp cgct Gly gitt Val 530 cct Pro aac; Lys gcc; Ala gtt Val1 atg Met cgtc Val1 gac Asp 435 c9gc Gly ttt Phe gcc Ala gtc Val tcc; Ser 515 gig Val1 gcc; Ala gc Ala t gc C ys ttt Phe aac As n gt g Val1 420 ct t Leu agc Ser aat Asn ctg Leu gat Asp 500 cgct Gly ttt Phe aca Thr aat Asn c ca Pro 580 gat Asp aagc Lys 405 gag Glu c9gc Gly ct c Val1 cgac Asp cgag Glu 485 att Ile aac; Lys gt C Val1 tat Tyr gat Asp 565 aac As n 1267 1315 1363 1411 1459 1507 1555 1603 1651 1699 1747 1795 1843 1891 Val Lys Pro Ala Leu Phe 570 tcgt aag cggc cgcc gCc icc; ctc tat gte gat ttg gce atg Cys Lys Gly Ala Gly Ser Val Tyr Val Asp Leu Gly Met atc; get ggg Met Aia Gly 595 WO 01/00804 WO 0100804PCT[IBOO/00922 gt a ValI gt g ValI ct g Leu 630 att Ile Gly cgc Arg ttt Phe ace Th r 710 ate Ile att Ile gag Glu tct Ser ttg Leu 615 t eg Ser ttg Leu t ac T yr ca g Gin att Ile 695 ttg Leu gt c Vali gat Asp 9gC Gly t eg Ser 600 gac Asp gct Ala cct Pro atc Ile cgt Arg 680 t tg Leu ctg Leu atc Ile gtc Val age Ser 760 ceg Pro tac Tyr gc Al a geg Al a acc Th r 665 ttg Leu gat Asp ga t Asp gaa Giu Gly 745 ec Pro t gt Cys cac His aat Asn gca Al a 650 etc Leu a ag Lys gag Glu ctt Le u cac His 730 cct Pro gcg Ala gag Gi u ttt Phe geg Aila 635 aag Lys 9gc Gly ctc Leu ccc Pro ttt Phe 715 cac His ggt Gly gaa Glu gtg Val1 ggt Gly 620 tat Tyr ate Ile ca g Gin gcc Aia ac Thr 700 gat Asp etc Leu gca Ala ctc tgC Cys 605 gge Gl y gag Glu gca Ala ceg Pro ace Thr 685 aca Thr caa Gin ggc Gly gg t Gi y ate gag Giu aag Lys ttt Phe aag Lys etc Leu 670 eac His ggc Gi y ctg Le u gtg Val1 tct Ser 750 aaa gge Gi y gae Asp ttc Phe agg Arg 655 ace Thr atg Met ctg Le u gt t Val1 etc Leu '735 gat Asp act aag Lys ate Ile geg Ala 640 ct Leu a eg Thr gea Al a ca e His ga t Asp 720 get Ala ggt Gly ga t cgt Arg gca Al a 625 geg Al a gte ValI ttg Leu gac Asp etc Leu 705 ga c Asp ca c His gge Gi y act ttt Phe 610 gac Asp aaa Lys gac Asp tee Ser aag Lys 690 get Ala ggc Gly get Ala teg Ser cca gat Asp gtg Val1 gat Asp gte Vai dly 675 gee Al a gat Asp aag Lys gac Asp at Ile 755 aca gag tee Giu Ser ttg ggg Leu Gly tea aag Ser Lys 645 ggc etc Gly Leu 660 ggt gaa Gly Giu aec ace Thr Thr gtg aaa Val Lys tet gte Ser Val 725 cae ate His Ile 740 gta tte Val Phe gga ege Gly Arg 1939 1987 2035 2083 2131 2179 2227 2275 2323 2371 2419 2463 Leu Ile Lys Thr Asp Thr Pro Thr 765 770 cac ctt aaa get tat gta gat tagtttctta tggaaaacec tgg His Leu Lys Ala Tyr Val Asp 775 780 <210> 146 c211> 780 <212> PRT <213> Corynebacterium glutamicun <400> 146 Met Gin Lys Ala Asp Ser His Asp Trp Ile Ser Val His Gly Ala Asn WO 01/00804 WO 0100804PCTIBOO/00922 Glu Thr Gly Thr His Gly Met Pro Ile 145 Lys Ser Asp Arg Asp 225 Lys Arg His Ala Asn Val Thr Phe Leu Ala Le u Gi y 130 Thr Arg Asp Gly Met 210 Phe Met Ile Ile Cys 290 Asn Phe Ile Val1 Gi u Asn Arg 115 Ala Val1 Tb r Ilie Ala 195 Tyr Thr Lys Gin Arg 275 Gly Leu Thr Al a Gin Gi y Pro 100 Ile Tyr Glu Gly Asp 180 Leu Ser Glu Ile Lys 260 Al a Gly Lys Gi y Ala GI y Ile Arg Leu Ser Lys Gly 165 Leu Thr Glu Giu Ala 245 S er Phe rhr Asn Val1 Glu Phe 70 Thr Ser Phe Phe Gi y 150 Met Lys Ile Ser Glu 230 Gly Met Val1 Arg Val Ser Ser 55 Met Th r Thr Se r Asn 135 Gi y Cys Glu Pro Gly 215 Arg Ile Leu Asp Leu 295 Ser Gly 40 Arg Pro Al a Val1 Arg 120 Val1 As n Pro Leu Gly 200 Leu His Asn Se r Arg 280 Ala Val1 25 Ser Arg S er Ile Gly 105 Ile Pro Thr Ala Phe 185 Tyr Phe Asn Met Lys 265 Ala Pro Arg Gly Leu Met Ile Thr Ala Ser Lys Cys 170 Asp Thr Asp Phe Thr 250 Asp Val1 His Ile Lys Ile Ala Val1 Ala Glu Val Arg 155 Glu Ala Pro Ala Leu 235 Tyr Arg Thr Ala Pro Lys Ser Ser Asn Glu Arg Pro Asp Gin Thr Asp Pro Asn 125 Ser Ala 140 Glu Lys Gly Met Ser Leu Gly Gly 205 Ala Lys 220 Tyr Leu Giu Gly Glu Gly Phe Ile 285 Leu Glu Arg Leu Thr Asp Giu Al a 110 Al a Se r Al a Gly Ser 190 Trp Pro Glu Leu Met 270 Pro Ser Asn Gly Lys Asn Ile Ala Glu Leu Cys Ala Met Giu Val Arg Asp Leu WO 01/00804 PCTIIB0000922 305 Ala Thr Tyr Gin Thr 385 Glu Val Va1 Phe Leu 465 His Val Ala Ser Asn 545 Ala Gly Gly I Lys Trp Ile Ala Ile Arg 370 Tyr Arg Leu Val Glu 450 His Gly Asp Gly Vai 530 Pro Lys Ala Met Leu Gir 355 Thr Va1 Met Val Asp 435 Gly Phe Ala Val Ser 515 Val Ala Ala Cys Met a Thr 340 Leu Lys Phe Asn Val 420 Leu Ser Asn Leu Asp 500 Gly Phe Thr Asn Pro I 580 Ala C Lys 325 Glu Asp Met Asp Lys 405 Glu Gly Va1 Asp Glu 485 Ile Lys Va1 ryr ksp 565 ksn 310 Thr Thr Arg Ile Glu 390 Leu His Pro Asp Arg 470 Ile Pro Ser Asp Thr 550 Val I Cys L Val Giu Ala Pr Leu Pro Arg 375 Pro Leu Lys Gly Lys 455 Ala Arg Leu Ser 31n 535 ;ly ~ys ,ys Asp Ala 360 His Thr Leu Pro Ala 440 Leu Ser Gly Gly Leu 520 Thr Met Pro Gly Asn 345 Gly Leu Ala Asp Glu 425 Gly Lys Leu Ala Va1 505 Ile Ala Leu Ala Ala 585 Ph( Thi G15 Gly Leu 410 Thr Ala Asp Lys Asp 490 Phe His Ile Asp Leu 570 Sly 315 Ser Val Leu Ser Leu 395 Arg Ile Gly Ser Glu 475 Arg Thr Glu His Ser 555 Phe Ser Glu Gl Ser Ala 380 His Asp Ala Gly Asp 460 Ser Asn Ala Ile Gly 540 Ile Ser Val lal Ile Gly 365 Leu Ala I Lys Ile Gly 445 Thr Val Asn Ile Pro 525 Ser Arg Pro Tyr Cys 605 Val Ala Pro Leu Gly 350 Gly Thr Tyr Gly Ala 430 Glu Val Arq Leu Ser 510 Arg Asn Lys ksn Val 590 Glu 335 Leu Glu Asp Asp Asn 415 Asp Ile Thr Ala Asn 495 Gly Asp Arg Ala Ser 575 Asp Gly 320 Leu Gly Ala Va1 Ile 400 Thr His Arg Gly Pro 480 Asn Va1 Glu Ser Phe 560 Glu Leu Lys ;iy Val Ser Ser Pro Cys 600 595 Arg Phe Asp Glu Ser Val Leu Asp Tyr His Phe Gly Gly Lys Asp Ile WO 01/00804 610 615 620 Ala Asp Val Leu Gly Leu Ser Ala Ala Asn Ala Tyr Glu Phe Phe Ala 625 630 635 640 Ala Lys Asp Ser Lys Ile Leu Pro Ala Ala Lys Ile Ala Lys Arg Leu 645 650 655 Val Asp Val Gly Leu Gly Tyr Ilie Thr Leu Gly Gin Pro Leu Thr Thr 660 665 670 Leu Ser Gly Gly Glu Arg Gin Arg Leu Lys Leu Ala Thr His Met Ala 675 680 685 Asp Lys Ala Thr Thr Phe Ile Leu Asp Giu Pro Thr Thr Gly Leu His 690 695 700 Leu Ala Asp Val Lys Thr Leu Leu Asp Leu Phe Asp Gin Leu Val Asp 705 710 715 720 Asp Gly Lys Ser Val Ile Val Ile Giu His His Leu Giy Vai Leu Ala 725 730 735 His Ala Asp His Ilie Ile Asp Val Gly Pro Gly Ala Giy Ser Asp Gly 740 745 750 Giy Ser Ile Val Phe Giu Gly Ser Pro Ala Giu Leu Ile Lys Thr Asp 755 760 765 Thr Pro Thr Gly Arg His Leu Lys Ala Tyr Val Asp 770 775 780 <210> 147 <211> 278 <212> DNA <213> Corynebacterium giutamicun <22 0> <221> CDS <222> <223> FRXA00829 <400> 147 ttg gat gag ccc acc aca. ggc ctg cac ctc get gat gtg aaa acc ttg Leu Asp Giu Pro Thr Thr Gly Leu His Leu Ala Asp Val Lys Thr Leu 1 5 10 ctg gat ctt ttt gat caa ctg gtt gat gac ggc aag tct gtc atc gte Leu Asp Leu Phe Asp Gin Leu Val Asp Asp Gly Lys Ser Val Ile Vai 25 atc gaa cac cac ctc gge gtg ctc get cac get gac eac ate att gat Ilie Giu His His Leu Gly Val Leu Ala His Ala Asp His Ile Ile Asp 40 gtc qgc cet ggt gca ggt tct gat ggt ggc tcg att gta ttc gag ggc PCT/IBOO/00922 WO 01/00804 Val Gly Pro Gly age ccc geg gaa Set Pro Ala Giu aaa gct tat gta Lys Ala Tyr Val PCT/IBOO/00922 Gly Ser Asp Giy Gly Ser Ile Val Phe GB-i Gly 55 ate aaa. act gat act cca aca gga cgc cac ctt Ile Lys Thr Asp Thr Pro Thr Gly Arg His Leu 70 75 tagtttctta tggaaaaccc tgg <210> 148 <211> <212> PRT <213> Corynebacterium glutamicui <400> 148 Leu Asp Giu Pro Thr Thr Gly Leu 1 5 Leu Asp Leu Phe Asp Gin Leu Val Ile Giu His His Leu Gly Val Leu 40 Val Gly Pro Gly Aia Gly Ser Asp 55 Ser Pro Ala Giu Leu Ile Lys Thr 70 Lys Ala Tyr Val Asp His Leu Ala Asp Val Lys Thr Leu 10 Asp Asp Gly Lys Ser Val Ile Val 25 Ala His Ala Asp His Ile Ile Asp Gly Giy Ser Ile Val Phe Giu Gly Asp Thr Pro Thr Gly Arg His Leu 75 <210> 149 <211> 1663 <212> DNA <213> Corynebacteriun giutamicum <220> <221> CDS <222> (101)..(1663) <223> FRXA00834 <400> 149 tgttttagcc atggacccca tactagggaq agttttgttt tggtqctaga aaaggttcac caagcgcgaa caggcctatg caaacggtac gatatgacae atg eaa aaa gct gat Met Gin Lys Ala Asp 1 tec eat gat tgg att tcg gtc cac ggt gcg aat gaa aac aac ctc aaa.
Ser His Asp Trp Ile Ser Val His Gly Ala Asn Glu Asn Asn Leu Lys 15 WO 01/00804 WO 0100804PCT/IBOO/00922 aat Asn gtg Val ga a Glu ttc Phe acc Thr tct.
Ser ttt Phe ttc Phe ggc Gi y 150 atg Met aaa Lys atc Ile t cg Ser gtg tcg Val Ser tcg gqa Ser Gly tca cgC Ser Arg atg ccg Met Pro acg gcg Thr Ala acg gtg Thr Val tcc cga Ser Arg 120 aac gic Asn Val 135 gga aac Gly Asn tgc cca Cys Pro gag ctt Glu Leu ccc ggt Pro Gly 200 ggc ctt Gly Leu 215 gtg Val1 tct.
Se r cgg Arg t eg Ser aic Ile qgt Gly 105 atc Ile ccc Pro acc Thr gcg Ala ttc Phe 185 t ac Tyr ttt Phe cg c Arg goc Gi y ttg Leu a tg Met atc Ile a cc Thr gcg Al a tct Ser aag Lys t gc Cys 170 gac Asp acc Thr gat Asp atc Ile aag Lys atc Ile gca Ala 75 gtc Val gca Al a gaa Glu gt t Val1 Arg 155 gag Giu gcc Ala cca Pro gct A~la cct.
Pro t cc Ser aac As n 60 agg Arg ga t Asp act Tb r ect Pro tcc Ser 140 gag Glu ggc Gly t cc Ser ggt Gly gcc Ala 220 aaa Lys tcg Se r 45 gaa Glu ccc Pro cag Gin gat Asp aac Asn 125 gca Al a aaa Lys atg Met ct C Leu gga Gly 205 a ag Lys agg Arg ct~g Leu acc Thr ga t Asp gag Giu gcc Ala 110 gcg Al a t cc Ser gct Ala ggc Gly t cc Ser 190 tgg Trp ccg Pro cgt Arg gtg Val1 tat Tyr gt t Val1 ca g Gin acc Thr ggt Gi y Gly acc Thr agg Arg 175 ctc Leu ag t Ser att Ile ct c Leu ttc Phe agc Ser gac Asp 80 atg Met ocg Ala ggc Gly gcc Ala ttc Phe 160 gcc Al a aac Asn tat Tyr a ag Lys acc Th r goC Gly act Thr cat His ggc Gly atg Met ccg Pro atc Ile 145 aaa Lys tca Ser qac Asp cgg Arg gat Asp 225 gtg Val aca Thr ttt Phe t tg Leu gca Ala ttg Leu gga GI y 130 acg Thr cgc Arg gac Asp ggc Gly atig Met 210 t tc Phe 9gt Gly gcg Ala ggt Gly a tc Ile cgg Arg t to Leu t cc Ser a ag Lys goc Gly 165 ctc Leu acc Thr ga a Gl u gaa Glu 211 259 307 355 403 451 499 547 595 643 691 739 787 gaa cgc cac aac ttc ctt tat ctt gag ccc acc aag atg aag atc Glu Arg 230 His Asn Phe Leu Tyr Leu Glu Pro Thr Lys Met Lys Ile wo 01/00804 WO 0100804PCT/IBOO/00922 ggc atc aac atg Gly Ile Asn Met acc tat gag ggt ctt etc ccc cgc att cag aaa tcc Thr Tyr Glu Gly Leu Ile Pro Arg Ile Gin Lys Ser 260 250 atg Met gtg Val1 cga Arg gct Aia 310 a cg Thr acc Thr cgc Arg atc Ile gaa Giu 390 t tg Leu cac His cca Pro gac Asp ttg tct Leu Ser gat cga Asp Arg 280 tta gcg Leu Ala 295 gag ttg Giu Leu gtg gaa Vai Giu ctg gat Leu Asp ccc gct Pro Ala 360 cgc cat Arg His 375 ccc acc Pro Thr ctg ctc Leu Leu eag ccg Lys Pro ggt gca.
Gly Ala 440 aag ctt.
aac Lys 265 9g Ala cca Pro tgc Cys gcc Ala aac Asn 345 ggc Gi y ttg Leu gce Ala gat Asp gaa.
Gl U 425 9gC Gly aaa gat Asp gtt Vai cat His gcg Ala ccc Pro 330 ttC Phe acg Th r ggc Gly ggt Gly ctt Leu 410 acc Thr gcg Ala gac cgC Arg acc Thr gcc Ala a tg Met 315 t cg Se r gt g Vali ttg Leu t ct Ser ttg Leu 395 cgc Arg atc Ile ggt Giy gc gaa Giu *ttc *Phe ttg Leu 300 gag Glu gt t Val1 gag Glu tct S er gca Ala 380 cac His gat Asp gcc Aia qga Gly gac: z Asp 1J 460 ggc Gly att Ile 285 gag Gi u gt c Val gct Ala etc Ile ggt Gly 365 ttg Leu gcc Ala aaa Lys att I le Igt 145 ~cc ~hr *atg Met 270 *cct *Pro tcc Ser cgt Arg ccc Pro ggt Gi y 350 ggt Gi y act Thr tac Tyr ggc Gi y gca Ala 430 gaa Glu gtg Val cag Gin t gc Cys aag Lys get Asp ct g Leu 335 ttg Leu gag Giu gac Asp ga c Asp eat Asn 415 get Asp att Ile act rhr aac Lys cct Pro at c Ile ttg Leu 320 ctc Leu ggc Gly gca Al a gt c Val1 att Ile 400 acc Thr cat His cgg Arg ggc Gi y cat ett His Ile gcg tgt Ala Cys 290 eat ggc Asn Gly 305 gcc eag Ala Lys acc gca.
Thr Ala tat etc Tyr Ile cag cgc Gin Arg 370 acc tat Thr Tyr 385 gaa cgc Giu Arg gtt tta.
Val Leu gtg gtg Val Val ttt gag Phe Giu 450 ctc cat Leu His cgt Arg 275 ggt Gly aa Lys tg Trp ct g Leu cee Gin 355 acc Thr gtt Val atg Met gtc Val1 ga c Asp 435 ggg Gly ttt Phe gcg Ala gga Gly aac As n at c Ile act Thr 340 ctc Leu aag Lys ttt Phe aac Asn gt g Val1 420 ct t Leu agc Ser eat Asn ttc Phe act Th r atc Ile aaa Lys 325 gaa Giu get Asp atg Met get Asp aag Lys 405 gag Giu ggg Giy gtc Val gac Asp 883 931 979 1027 1075 1123 1171 1219 1267 1315 1363 1411 1459 1507 1555 Lys Leu Lys Asp Ser 455 465 cgg gcg tca ttg aag gee tcc gtg cgt gcg ccg cat ggc gcc ctg gag WO 01/00804 PCTIBOOIOO922 Arg Ala Ser Leu Lys Glu Ser Val Arg Ala Pro His Gly Ala Leu Giu 470 475 480 485 atc cgc ggg gcc gat cga aat aat ttg aac aat gtg gat gtc gat att 1603 Ile Arg Gly Ala Asp Arg Asn Asn Leu Asn Asn Val Asp Val Asp Ile 490 495 500 ccg ctc ggc gtg ttc acg gcg att tcc ggc gtt qca ggt tcg ggt aag 1651 Pro Leu Gly Val Phe Thz Ala Ile Ser Gly Val Ala Gly Ser Gly Lys 505 510 515 tcc tcg ttg att 1663 Ser Ser Leu Ile 520 <210> 150 <211> 521 <212> PRT <213> Corynebacteriun giutamicut <400> 150 Met Gin Lys Ala Asp Ser His Asp 1 5 Giu Asn Asn Leu Lys Asn Val Ser Thr Val Phe Thr Gly Val Ser Gly S 40 Gly Thr Ile Ala Ala Giu Ser Arg A 55 Thr Phe Val Gin Gly Phe Met Pro S 70 His Leu Giu Gly Ile Thr Thr Ala 1.
Gly Ala Asn Pro Arg Ser Thr Vai G 100 Met Leu Arg Ile Leu Phe Ser Arg I] 115 120 Pro Gly Ala Tyr Ser Phe Asn Val Pr 130 135 Ile Thr Val Giu Lys Gly Gly Asn Th 145 150 Lys Arg Thr Giy Gly Met Cys Pro Al 165 Ser Asp Ile Asp Leu Lys Giu Leu Ph4 180 18~ Prp Ile Ser Val 10 Pal Arg Ile Pro 25 er Gly Lys Ser .rg Leu Ile Asn er Met Ala Arg 75 le Ile Val Asp 90 ly Thr Ala Thr *e Ala Giu Pro Ser Val Ser 140 r Lys Arg Giu L 155 a Cys Giu Giy M 170 Asp Ala Ser L 5 Hi Ly Se~ Gi L Pro Gin Asp Isn 125 l.a ,ys 'et eu s Gly Ala Arg Arg Leu Val aThr Tyr Asp Val Giu Gin Ala Thr 110 Ala Gly Ser Gly I Ala Thr I 1 Gly Arg A 175 Ser Leu A 190 Asn Leu Phe Ser Asp Met Ala 'he l1a sn WO 01/00804 WO 0100804PCT/IBOO/00922 Asp Gly Ala Leu Thr Ile Pro 195 Gly Tyr 200 Thr Pro Gly Gly Trp Ser Tyr 205 Arg Asp 225 Lys Arg His Ala Asn 305 Ala Thr Tyr Gin Thr 385 Glu Val Val Met 210 Phe Met Ile Ile Cys 290 Gly Lys Ala Ile Ar g 370 Tyr PArg Leu lal1 Tyr Thr Lys Gin Arg 275 Gly Lys Trp Leu Gin 355 Thr Val Met Val Asp 435 Se Gi.
Ile Lys 260 Al a Gi y Asn I le Thr 340 Leu Lys Phe Asn Val1 420 eu *Giu 1Giu Ala 245 *Ser *Phe Thr Ile Lys 325 Glu Asp Met Asp Lys2 405 Glu Gly Se~ Gli 23( G15~ Met Val1 Arg Ala 310 Thr Thr Arg Ile Glu 390 Leu H(is Pro Gl1 211 iArc Sle Leu Asp Leu 295 Glu Val1 Leu Pro Arg 375 Pro Leu Lys Gly Lys 455 Leu Phe Asp His Asn Phe Asn Met Thr 250 Ser Lys Asp 265 Arg Ala Val 280 Ala Pro His Leu Cys Ala Glu Ala Pro 330 Asp Asn Phe 345 Ala Gly Thr 360 His Leu Gly Thr Ala Gly Leu Asp Leu 410 Pro Glu Thr 425 Ala Gly Ala 440 Leu Lys Asp Al Let 231 Tyi Arc Thr Ala Met 315 Se r Val1 Leu Ser Leu 395 Arg Ile Gly Ser iAla 220 j Tyr Glu Glu *Phe Leu 300 Glu Val Glu Ser Al a 380 His Asp Ala Gly Asp 460 Lys Leu Gl y Gly Ile 285 Glu Val Ala Ile Gl y 365 Leu Ala Lys I le Sly 445 rhr Val1 Pro Glu Leu Met 270 Pro Ser Arg Pro Gi y 350 Gly Th r Tyr Gly Al a 430 Glu Val Arg Ile Pro Ile 255 Gin Cys Lys Asp Leu 335 Leu Glu Asp Asp Asn 415 Asp Ile Th r Al a Lys Thr 240 Pro Lys Pro Ile Leu 320 Leu Gly Ala Val Ile 400 Thr His Arg Gi y Pro 480 Phe Giu Giy Ser Val Asp 450 Leu His Phe Asn Asp Arg Ala Ser Leu Lys Glu Ser 465 470 475 His Giy Ala Leu Ile Arg Giy Ala Asp 490 Arg Asn Asn Leu Asn Asn 495 WO 01/00804 Val Asp Val Asp Ile Pro Leu Gly Val Phe Thr Ala Ile Ser Gly Val 500 505 510 Ala Gly Ser Gly Lys Ser Ser Leu Ile 515 520 <210> 151 <211> 864 <212> DNA <213> Corynebacterium glutamicun <220> <221> CDS <222> (101)..(841) <223> RXA00995 <400> 151 gtcggatcat ctggagggga acacccacac gccttctaga agatacaggc aaaagctc acgaagatgc tttcttggct gccattgacg gggiaaggtc atg aac cct cac tat Met Asn Pro His Tyr PCT/IBOO/00922 at ctg Leu cgt Arg ttt Phe acc Thr ttg Leu gag Glu t ac Tyr ctt Leu t cc Ser tat Tyr at t Ile atg Met cgc Arg qgg GI y goc acg Ala Thr atc gcg Ile Ala tac atg Tyr Met tcc acg Ser Thr acg tcg Thr Ser ttg tgg Leu Trp gtg gc Val Ala gt c ValI ct g Leu tat Tyr gt c Val1 gtg ValI acc Thr ttc Phe aaa Lys att Ilie t cc Ser atg Met acg Thr 75 a cg Thr 9qC Gly cga Arg ctt Leu tcc Ser atc Ile 60 atg Met aac Asn atc Ile gt C ValI ct a Leu aca Th r 45 gca Ala caa Gin at t Ile atg Met ctg Leu gca Aia 30 ccg Pro gtg Val1 aga Arg ca c His geg Ala 110 ctg cag Leu Gin 15 ccc gtg Pro Val gca ggc Ala Gly ttc ccc Phe Pro gaa cgc Glu Arg 80 cgc gtt Arg Val.
95 gtg gcg Val Ala 1 ctg aaa Leu Lys gcg ttg Ala Leu acc cag Thr Gin 50 ttg atg Leu Met 65 aac gct Asn Ala gat ttg Asp Leu caa tct Gin Ser gcc gat Ala Asp 20 atg tcg Met Ser 35 ctg ttt Leu Phe ctc atg Leu Met gga acg Gly Thr atc ggt Ile Gly 100 ttg ctc Leu Leu 115 aaa Lys ct g Leu aag Lys ttt Phe ctc Leu ggc Gly atg Met 115 163 211 259 307 355 403 451 499 105 gtg ctc acc ctt cgg tat ctc ctg ggt gtg gaa acc gaa tcg gag tgg Val Leu Thr Leu Arg Tyr Leu Leu Gly Vai Glu Thr Giu Ser Giu Trp t gg T rp, ett Leu 150 caa Gin ctg Leu gt g Val1 acg Th r ttt Phe 230 acc Thr WO 01/00804 att tet acg etc att get gcg atc Ile Ser Thr Leu Ile Ala Ala Ile 135 140 ggc ctg ttg agc tet qcg ttt gee Gly Leu Leu Ser Ser Ala Phe Ala 155 aeg ctg ccg ttg ctt att ttg ccc Thr Leu Pro Leu Leu Ilie Leu Pro 170 atc cca cgg gat gat ctg ccg gat Ilie Pro Arg Asp Asp Leu Pro Asp 185 190 ttg ccg ctg tee tat gca gtt gat Leu Pro Leu Ser Tyr Ala Val Asp 200 205 gga atc gga eag caa gta gtg gte Gly Ile Gly Gin Gin Val Val Vai 215 220 gee gtg agc ttc ctg ctg gtg gcg Ala Val Ser Phe Leu Leu Val Ala 235 cgc tagattacte ttceagcgag gtg Arg ace ggt Thr Gly age act Ser Thr 160 cag tte Gin Phe gtg ttg Val Leu gca gcg Ala Ala aac att Asn Ile geg eta Ala Leu 240 PCT/IBOO/00922 tct 547 Ser ate 595 Ile 165 ttg 643 Leu aat 691 As n egg 739 Arg geg 787 Al a atg 835 Met 245 <210> 152 <211> 247 <212> PRT <213> Corynebacterium giutarnicum <400> 152 Met Asn Pro His Tyr Leu Leu Ala Thr 1 Leu Lys Ala Asp Lys Arg Ser Ile Ala Ala Leu Met Ser Leu Phe Tyr Tyr Met Thr Gin Leu Phe Lys Thr Ile Ser Thr Leu Met Leu Met Phe Leu Met Thr Ser 70 Asn Ala Gly Thr Leu Giu Arg Leu Trp Lys Ile Ser Met Thr Thr Asp Gin Thr Leu 145 Giu Leu Arg Leu Al a 225 Ser WO 01/00804 Leu Ilie Gly Gly 100 Ser Leu Leu Met 115 Giu Ser Giu Trp 130 Ile Gly Val Ser Phe Gin Ala Ile 165 Leu Cys Gly Leu 180 Trp Vai Ser Asn 195 Glu Ala Ser Arg 210 Ilie Cys Ala Ala Met Pro Arq Met 245 Tyr ValI Trp Leu 150 Gin Leu Val1 Thr Phe 230 Tb r Val1 Thr 120 Ser Leu Leu Pro Pro 200 Ile ValI Ala 105 Leu Th r Leu Pro Arg 185 Leu Gly Ser Gly Tyr Ile Ser 155 Leu Asp Tyr Gin Leu 235 PCTIIBOO/00922 Al a Giu Gly Thr 160 Phe Leu Ala Ile Leu 240 <210> 153 <211> 1353 <212> DNA <213> Corynebacterium glutanicun <220> <221> CDS <222> (101)..(1330) <223> RXN00803 <400> 153 tcatccttcc ttagctcgcg tgagcttccc aagcgtaagc cggccqttct gttaaagatt ggtctggcca tttcctccat ctt aac atg tct gac atg gtg gcg aac aaa cgg Leu Asn Met Ser Asp Met Vai Ala Asn Lys Arg 15 tgg cta gcg gta gct tta tcg qtc ttt acg qtc Trp Leu Ala Val Ala Leu Ser Val Phe Thr Val 30 gaa ttc act ccc ttg ctg gtg ttt tac cga ggt acccccgtgt gagggcataa atg ggg gtg tcc gcg Met Gly Val Ser Ala 1 gca cag cgt aaa 9tc Ala Gin Arg Lys Val gcg tgg ggt ggc aat Ala Trp Gly Giy Asn gaa ggg ttc ttt acc WO 01/00804 Giu Phe Thr Pro PCT/IBOO/00922 Leu Leu Val Phe Tyr Arg Gly Giu Gly Phe Phe Ser aac ctg ttc atc gac ctt. tti Asn qt a Val gcc Ala att Ile ctg Leu att Ile gct Ala 150 ggc Gly cag Gin ttg Leu aag Lys cgaI Arg 230 Lei
GI~
gt C Val gcc Ala t cg Ser aag Lys 135 ggt Gi y c ca Pro ttg Leu ct t Leu gga Gl5 ttc Phe u Phe 5 ~Leu atg *Met tcg ISer gga *Giy 120 gag Glu gca Ala gcg Ala gca1 Ala att Ile 'I 200 tca t Ser P ttg t Leu P Ile ctg Leu t tg Leu ggt Gi y 105 att.
Ile ctt Leu aaa Lys ct t Leu :at ['yr 185 ica hr ;tc ~he tt 'he Asp gca Ala cct Pro gaa Giu tcg Ser t ca Ser cgc Arg gct A.1a 170 gtt Val gcg Al a Leu Lei gct ggl Ala GI' 75 gcg ccE Ala Prc gaa acc Giu Thr gtg ggc Val Gly tcg tcg Ser Ser 140 gca tcg Ala Ser 155 ggt gtg Gly Val ttg cac Leu His ccg gaa Pro Glu qctg gtg ttt ui Leu Val Phe t cct tta tct y' Pro Leu Ser ttg atc gcg Leu Ile Ala 95 gcc atc ctg Ala Ile Leu 110 atg gtg atg Met Val Met 125 cgg ttt gag Arg Phe Glu atg tct ttg Met Ser Leu atg gca cag Met Ala Gin 175 att att ctc Ile Ile Leu 190 act cgt caa Thr Arg Gin 205 qtg ctt gtg Val Leu Val cca att gga Pro Ile Gly tal Ty ga Asi atc IlE att Ile aca Thr cca Pro acc Thr 160 tgg Trp act Thr t ca Ser cca Pro :cg t gcc Al1a 61 *cgc >Arc ttc Leu gcc Ala gcg Ala ggg Gly 145 ggt Gly ct g Leu ctg Leu gcq Ala tct Ser 225 t gg atc gga Ile Gly tat ggc Tyr Gly gqt tcc Gly Ser att. ggt Ile Gly 115 gga ggt Gly Gly 130 gtg aaa Val Lys ggt ttt Gly Phe cca cta Pro Leu att ttg Ile Leu 195 cac ctg His Leu 210 gca cta Ala Leu2 gtt ttc gt a Val cga Arg gcg Ala 100C cga Arg toc Se r acc Th r gcg Ala cct Pro 180 ttc Phe aaa Lys gac ksp ;gt ;iY gcg *Ala Cgt Arg ttg *Leu gt g Val1 tgg Trp agt Ser ctc Leu 165 gga Gi y Ccg Pro act Thr aag Lys gog Al a 245 307 355 403 451 499 547 595 643 691 739 787 835 t :gg tca gat 'rp Ser Asp 220 jtg gtt gct 'al Val Ala 235 ?ro Trp Val Phe ~40
C
2 ttc act gcc tac gca gtt ttg ccg Phe Thr Ala Tyr Ala Val Leu Pro tcg cag ctg cgt gac atg Ser Gin Leu Arg Asp Met 250 255 260 tct gca ccc gtt gcg tat tct gcg ctg atc gct ttg gtt acc tta ggt Ser Ala Pro Val Ala Tyr Ser Ala Leu Ile Ala Leu Val Thr Leu Gly tct Ser aaa Lys atc Ile 310 gt t Val1 ggg Gly ctg Leu gcc Al a 9gc Gly 390 WO 01/00804 265 ;a ttt ggt atc caa .y Phe Gly Ile Gin 280 :t cgc ggq ccg att ir Arg Gly Pro Ile Ic qcg gtg atc gtg .y Ala Val Ilie Val 315 rc tgc atg gcc ctc .y Cys Met Ala Leu 330 g gcg gaa act caa u Ala Giu Thr Gin 345 :g ggt att ttc tac xr Gly Ile Phe Tyr 360 g atg acc tgg ttg u Met Thr Trp Leu t ggt gcg gtg atg e Gly Ala Val Met 395 t tc Phe 285 gcc Ala atg Met ct g Leu att Ile ctg Leu 365 caa Gin act 270 ggt GI y atg Met aac As n tct gct Ala 350 a cq Thr tgg Trp att caa Gin gt c Val cat His 320 9gc Gly cct Pro gt a Val1 agt Ser ctg atg Met 290 qt C Val1 tgg Trp tgt Cys gat Asp atg Met 370 ccg Pro att Ile a cc Thr ggC Gly gcg Ala ttc Phe 340 gca Ala ttt Phe atg Met agt Se r PCT/IBOO/00922 979 1027 1075 1123 1171 1219 1267 1315 1353 Thr Ile Cys Leu Ile agt gca cgc cga Ser Ala Arg Arg tgagaaacaa. ctaaagtgag cca <210> 154 <211> 410 <212> PRT <213> Coryriebacterium glutamicum <400> 154 Met Gly Val Ser Ala Leu Asn Met Ser Asp Met Val Ala Asn Lys Arg 1 5 10 Ala Gin Arg Lys Val Trp Leu Ala Val Ala Leu Ser Val Phe Thr Vai 25 Ala Trp Gly Gly Asn Glu. Phe Thr Pro Leu Leu Val Phe Tyr Arg Gly 40 Giu Gly Phe Phe Ser Asn Leu Phe Ile Asp Leu Leu Leu Val Phe Tyr 55 WO 01/00804 WO 0100804PCT/IBOO/00922 Ala Ile Gly Val Ala Val Gly Leu Leu Ala Ala Gly Pro Leu Ser Arg Le u Al a Al a Gly 145 Gly Leu Leu Ala Se r 225 Trp Leu Leu Ile Thr 305 Pro Leu 75 Tyx GlN Ile Gly 130 Val Gly Pro Ile His 210 Ala Val1 Arg Val1 M4et 290 Vli Trp 'ys -Gly Ser Gly 115 Giy Lys Phe Leu Leu 195 Le u Leu Phe Asp Thr 275 Gly Ile Trp Met Arg Ala 100 Arg Ser Th r Ala Pro 180 Phe Lys Asp Gly Met 260 Leu Th r Gi y Al a ?he Arc Leu ValI Trp Se r Leu 165 Gly Pro Thr Lys Al a 245 Val1 Gly Ser Met Leu 325 Met Ala Ile Leu Ile Ala 150 Gly Gin Leu Lys Arg 230 Al a Ser Ser Lys Ilie 310 Val Gly I Val Ala Ser Lys 135 Gly Pro Leu Leu Gly 215 Phe Phe Al a Gly Th r 295 .,ly Aly .e u *Met Ser *Gly 120 Giu Ala Ala Ala Ile 200 Ser Leu Thr Pro Phe 280 Arg Al a Cys Ala *Leu *Gly 105 Ile Le u Lys Leu Tyr 185 Thr Phe Phe Al a Val 265 Gi y Gly Vai Met Glu 345 Pro GEu Set Ser Arg Ala 170 ValI Ala Trp Val1 Tyr 250 Al a Ile Pro Ile ~Ia 330 rhr Ala Glu Val Ser Ala 155 Gly Leu Pro Ser Val1 235 Ala Tyr Gin Ile Val 315 Leu Gin Pro Thr Gi y Ser 140 Se r Val1 His Glu Asp 220 Al a Val Ser Gin Leu 300 Val1 Gly Leu *Ala Met 125 *r Ag Met Met Ile Thr 205 Val Pro Leu Ala Phe 285 AlaI Met Leu Ile Ile Ile 110 Val Phe Ser Ala Ile 190 Arg Leu Ile Pro Leu 270 Gi y Met Asn Ser ~Ila 350 Ala Leu Met Gi u Leu Gin 175 Leu Gin ValI Cl y Se r 255 Ile Pro Phe Pro Tyr 335 Pro Asp Ile Ile Thr Pro Thr 160 Tip Thr Ser Pro Pro 240 Gin Ala Gin Val His 320 Giy Pro 340 Ilie Asp Met 355 Ala Gly Leu Thr Ile Phe Tyr Cys Thr Tyr Vai WO 01/00804 Gly Met Val Phe Pro Ala Leu Met Thr Trp Leu Asn Gin Trp Leo Ser 370 375 380 Tyr Pro Phe Met Leu Gly Phe Gly Ala Val Met Ala Thr Ile Cys Leu 385 390 395 400 Ile Ile Val Ser Phe Ser Ala Arg Arg Phe 405 410 PCT/IB00/00922 <210> 155 <211> 703 <212> DNA <213> Corynebacteriun glutamicum <220> <221> CDS <222> (101)..(703) <223> FRXA00803 <400> 155 tcatccttcc ttagctcgcg tgagcttccc aagcgtaagc acccccgtgt gagggcataa cggccgttct gttaaagatt ggtctggcca tttcctccat atg ggg gtg tee qcq 11 Met Gly Val Ser Ala ctt Leu tgg Trp ga a Glu aac Asn gt a ValI gcc Ala att Ile aac As n et a Leu ttc Phe ctg Leu ggt Gly gtc Val1 gcc Ala t Ct Ser gta Val1 ccc Pro at c Ile ct g Leu ttg Leu ggt Gly 105 at g Met tta Leu ctg Leo ctt Leu gct Ala 75 g9cg Al a gaa Glu 9c9 Al a gtc Val ttt Phe ctg Leo Cct Pro ttg Leu gcc Ala aac Asn ttt Ph e tac Tyr gtg Val tta Leu atc Ile atc Ile 110 cgg Arg gtc Val1 qgt Gly tat Tyr gac Asp 80 ate Ilbe att Ile gtc Val1 aat Asn agc Ser gcg Al a cgt Arg ttg Leu gtg ValI ctg tcg gga Leo Ser Gly att tcg gtg ggc atg gtg atg aca gcg Ile Ser Val Gly Met Val Met Thr Ala gga ggt tcc tgg Gly Gly Ser Trp WO 01/00804 120 aag gag ctt Lys Glu Leu 135 ggt gca aaa Gly Ala Lys cca gcg ctt Pro Ala Leu ttg gca tat Leu Ala Tyr 185 ctt att aca Leu Ilie Thr 200 PCT/IBO0100922 tca tcg tcg Ser Ser Ser 140 cgc gca tcg Arg Ala Ser 155 gct ggt gig Ala Gly Val 170 gtt ttg cac Val Leu His ttt gag cca ggg ?he Glu Pro Gly 145 tct ttg ace ggt Ser Leu Thr Gly 160 gca cag tgg ctg Ala Gin Trp Leu 175 att ctc act ctg Ile Leu Thr Leu 190 ace agt Thr Ser gcg ctc Ala Leu 165 cct gga Pro Gly 180 tic ccg Phe Pro <210> 156 <211> 201 <212> PRT <213> Corynebacterium glutamicum <400> 156 Met Gly Val Ser Ala Leu Asn Met Ser Asp Met Val Ala Asn Lys Arg Thr Val Arg Gly Phe Tyr Ser Asp Ala Ile Leu Ile Met Thr Glu Pro Leu Thr WO 01/00804 WO 0100804PCT/IBOO/00922 145 150 155 160 Gly Gly Phe Ala Leu Gly Pro Ala Leu Ala Gly Val Met Ala Gin Trp 165 170 175 Leu Pro Gin Pro Gly Gin Leu Ala Tyr Val Leu His Ile Ile Leu Thr 180 185 190 Leu Ilie Leu Phe Pro Leu Leu Ile Thr 195 200 <210> 157 <211> 1014 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> (991) <223> RXA01407 <400> 157 atccggggaa cggatcccaa agatctcctt gatgccatcg cgtttttaac ctggeeagct ctggttgccc cagtgatcgc cccacttctg ggaggtettc ttg caa gat ace att Leu Gin Asp Thr Ile ggt Gly atc Ile aag Lys gcg Ala ctt Leu ttt Phe atc Ile cga tgg Arg Trp get gga Ala Gly ttt gat Phe Asp gcc gtg Ala Val ate tgt Ile Cys gtg cgc Vai Arg cgc atc Arg Ilie 105 atc ttc Ile Phe cta ttc Leu Phe cgg cca Arg Pro att gcg Ile Ala gca tgc Ala Cys 75 tgg ctg Trp, Leu cca ggt Pro Giy ctc Leu atc Ile ggt Gly gag Giu ctc Leu cga Arg ttc Phe ctc aac Leu Asn cag ccc Gin Pro 30 ttc etc Phe Leu 45 tta att Leu Ile gtc tta Val Leu gtt cca Val Pro ega gtg Arg Val 110 gtg ccc Val Pro i5 sag aac Lys Asn gge gea Gly Ala tgc age Cys Ser agt gct Ser Ala ggc cga Gly Arg 95 ggt aat Gly Asn gga Giy gee Al a etg Leu agt Ser gt g Val1 ttt Phe tee Ser atc Ile gt g ValI gt g Val ceg Pro gta Val1 gat Asp gga Gly 115 ate Ile at Asn atg Met gee Aia t ge Cys ctc Leu 100 agt Ser 115 163 211 259 307 355 403 451 WO 01/00804 WO 0100804PCT/IBOO/00922 tac cgc tic; Tyr Arc; Leu caa Gin cgca Al a 150 ati Ile Gi y ctg Leu ctc Leu gaa Glu 230 ggc Gly ccc Pro cct Pro 120 gcg Ala ttc Phe cgc Arg ttg Leu ci c Leu 200 tic Phe acc Thr tct Ser gcc Ala atc Ile 280 gta Val ttt Phe gca Ala t gg Trp gta Val1 185 aic Ile agc Ser agc Ser tic; Leu aac Asn 265 gg C GI y 125 130 aic acc gca Ile Thr Ala gca cca tic atc; tic act tic; ctc ttc Ala Pro Phe Met Phe Thr Leu Leu Phe 99g9 Gly ggc Gly aat Asn 170 ttg Leu gt g Val1 cc Ala aac Asn gt Gly 250 icgg Trp gca Al a tcgg Trp aac Asn 155 tic Phe gca Ala ctg Leu tac Tyr gcc Al a 235 at t Ile gca Al a cta ict Se r 140 gig Val1 aaa Lys act Thr cig Leu aac Asn 220 aac As n gcc; Al a tc Phe t ci gca aca Ala Thr cgca atc Ala Ile cca gta Pro Val iii tic; Phe Leu 190 cic tt teu Phe 205 acc tig Thr Leu gig tta Val Leu gia gca Val Ala cca cic; Pro Leu 270 tic; cct tta Leu aaa Lys cic; Leu 175 tic Phe gt t Val1 cag Gin ica Se r gtc Val 255 gca Al a cgc gcgi Gi y 145 ttc Phe ttt Phe cgt Arc; Gly gic Val1 225 acc Thr cgcc Ala gcg Ala ggc Gi y aig Met acg Thr aac Asn gat Asp 195 ta Leu aic Ile cac His icc Ser tic Phe 275 gcc Ala Leu Ser Leu Pro Arg Asp 285 iii icc tcc ici iacgaaaccca citcicgaaa; gia Phe Ser Ser Ser 295 <210> 158 <211> 297 <212> PRT <213> Corynebacteriun gluiamicum <400> 158 Leu Gin Asp Thr Ilie Gly Cys Arg Trp Ilie Phe Leu Leu Asn Val Pro 1 5 10 1014 WO 01/00804 WO 0100804PCTI[BOO/00922 Leu Gly Ile Ile Ala Ile Met Ala Gly Leu Phe Ile Gin Pro Lys Asn 25 Thr Ala Val Asn Val Lys Arq Phe Asp Arg Pro Gly Phe Leu Gly Ala 40 Met Len Vai Met Val Ala Gin Ala Val Ile Ala Glu Len Ile Cys Ser 55 Arg Ser Pro Ala Ala Leu Thr Ile Cys Ala Cys Leu Val Len Ser Ala 70 75 Ala Val Val Cys Gly Phe Val Val Arg Trp Leu Arg Val Pro Gly Arg 90 Leu Phe Asp Leu Ser Ile Met Arg Ile Pro Giy Phe Arg Val Gly Asn 100 105 110 Ser Ser Giy Ser Ilie Tyr Arg Len Val Ile Thr Ala Ala Pro Phe Met 115 120 125 Phe Thr Len Len Phe Gin Val Ala Phe Gly Trp Ser Ala Thr Leu Ala 130 135 140 Gly Ala Met Vai Val Ala Len Phe Ala Giy Asn Val Ala Ile Lys Pro 145 150 155 160 Phe Thr Thr Pro Ilie Ile Lys Arg Trp Asn Phe Lys Pro Val Len Vai 165 170 175 Phe Ser Asn Ala Ala Giy Ala Leu Val Len Ala Thr Phe Len Phe Val 180 185 190 Arg Ala Asp Thr Pro Leu Vai Leu Ile Val Len Leu Leu Phe Vai Ser 195 200 205 Gly Ala Leu Arg Ser Len Gly Phe Ser Ala Tyr Asn Thr Len Gin Phe 210 215 220 Val Asp Ile Ser Pro Giu Gin Thr Ser Asn Ala Asn Val Leu Ser Ala 225 230 235 240 Thr Leu His Gin Leu Gly Met Ser Leu Gly Ile Ala Vai Ala Val Ile 245 250 255 Ala Met Ser Len Ala Pro Thr Ala Asn Trp Ala Phe Pro Len Ala Ala 260 265 270 Ala Len Phe Leu Ile Pro Len Ilie Gly Ala Len Ser Leu Pro Arg Asp 275 280 285 Gly Gly Ala Arg Ala Phe Ser Ser Ser 290 295 <210> 159 WO 01/00804 <211> 324 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> (301) <223> RXA01408 <400> 159 cgcatagagt tatctcgaaa ctaccaagae ggtttctttt gaccgtcttt caccctttca tctgattgga categacgcc PCT/IBOO/00922 etttagatct aaggaggaga atg cge aat gat cgg Met Arg Asn Asp Arg 1 tee ttt age gtt ccc att gcq cta ett gcc gcg gga gca etg ttt eta Ser Phe Ser Val Pro Ile Ala Leu Leu Ala Ala Gly Ala Leu Phe Leu 15 gaa atc etc gac ggc ace ate etg aca ace gea gtg cca gct att get Giu Ile Leu Asp Giy Thr Ile Leu Thr Thr Ala Val Pro Ala Ilie Ala 30 cgt gac tte ggt att gac gcc gtg gat gte age att gca ctg gtt get Arg Asp Phe Gly Ile Asp Ala Val Asp Val Ser Ile Ala Leu Val Ala 45 tac ttg gca gcc gca gca get ggc att ccg etg cag ggt ggc Tyr Leu Ala Ala Ala Ala Ala Gly Ile Pro Leu Gin Gly Gly 60 tagcggateg atttggtgtg cgc <210> 160 <211> 67 <212> PRT <213> Corynebacterium giutamicum <400> 160 Met Arg Asn Asp Arg Ser Phe Ser Val Pro Ile Ala Leu Leu Ala Ala 1 5 10 Gly Ala Leu Phe Leu Glu Ile Leu Asp Gly Thr Ile Leu Thr Thr Ala 25 Val Pro Ala Ilie Ala Arg Asp Phe Gly Ile Asp Ala Val Asp Val Ser 40 Ile Ala Leu Val Ala Tyr Leu Ala Ala Ala Ala Ala Gly Ile Pro Leu 55 Gin Gly Giy WO 01/00804 <210> 161 <211> 1275 <212> DNA <213> Corynebacterium qiutamicum <220> <221> CDS <222> (101)..(1252) <223> RXN01922 <400> 161 acactccttt ggtcacctgg tttggttgag ggaaacagac PCT/IBOO/00922 cgcccaagaa cccaagaaat cccaagaaaa catgctgctt atgaattaaa gtqagcaccc atg aga tca Met Arg Ser qcc Ala tgg Trp tta Leu ctg Leu ttt Phe gga GI y gga GI y acc Thr ggc Gly aat cgc Asfl Arq gca gcc Ala Ala gac gta Asp Val gga ctt Gly Leu ggt gcc Gly Ala aac ctt Asn Leu cga ttc Arg Phe gca tgg Ala Trp 120 att att Ile Ile 135 gtc ttc Val Phe aat cat Asn His tca agc Ser Ser ctt cca Leu Pro cgc atg Arg Met tct ctt Ser Leu atc gtt Ile Val 105 gcg ggc Ala Gly ctg acc Leu Thr ata Ile ttc Phe gt g Val1 agt Se r gtg Val1 75 tta Leu ggt Gi y aga Arg gcc Al a ggt Gly gcg Al a ct g Le u t tg Leu 60 gta Val1 gcg Ala ctg Leu ttg Leu ggt Gly 140 gtt Val1 t ca Se r gtc Val1 45 ctc Leu ctc Leu ttt Phe ggc Gly cgc Arg 125 t tc Phe acc Thr gtg Val1 30 aac Asn gca Ala a cc Thr cat His gt t Val1 110 gga Gly atg Met atc ctg Ile Leu 15 ttg gtg Leu Val ggc gct Gly Ala ggc ggt Gly Gly gga ggt Gly Gly 80 gat ggt Asp Gly 95 gga tta Gly Leu gca agc Ala Ser atg ggg Met Gly 1 ctg ttt Leu Phe ttg atc Leu Ile ttt ggt Phe Gly gtg ctt Val Leu gta ctt Val Leu cct tcc Pro Ser gtc gtc Val Val ggc gtg Gly Val 130 ccg att Pro Ile 145 act Thr cgt Arg att Ile gcc Al a tct Se r ct c Leu agc Ser 115 aca Thr gtq Val gga aac Gly Asn gca gqa Ala Gly gaa caa Glu Gin tat gca Tyr Ala gac cgt Asp Arg gcg ctt Ala Leu ctg gta Leu Val 100 gcg ggc Ala Gly ttg gcc Leu Ala aca agt Thr Ser 115 163 211 259 307 355 403 451 499 547 ggg ttg ggg atg gcg Gly Leu Gly Met Ala 150 tcg aca agc att att acg ccc ttt gcc ata agc Ser Thr Ser Ile Ile Thr Pro Phe Ala Ile Ser WO 01/00804 WO 0100804PCT/IBOO/00922 gt t Val1 gcc Ala gaa Gi u tgg Trp atc Ile 230 gcg Ala ttc Phe gcg Al a ct t Leu ctg Leu 310 cgt Arg qgg Gly att Ile gcc ctc tcg ctg atc gcg gtg gtt gtq gga ttt gcg ctt Ala Leu Ser Leu Ile Ala Val Val Val Gly Phe Ala Leu cgc Arg cga Arg gtg Val1 21 gac Asp atc Ile gcg Ala ggt Gly ttc Phe 295 cgc Arg ggc Gly ct g Leu ccg Pro agc Ser agc Ser 200 ttc Phe tC Ser gcC Ala t gg T rp ttt Phe 280 gt t Val1 gaa Gi u acc Thr cca Pro ctg Leu 360 acc Thr 185 atg Met agc Ser acc Thr ttc Phe .ggt Gi y 265 gcg Al a atc Ile Gly ggC Gly gt g Val1 345 tac Tyr 170 ccg Pro aaa Lys tgc Cys ttc Phe agc Ser 250 cgt Arg ctg- Leu gcc Ala ctc Leu atc Ile 330 ctt LeuI gcg Ala I agc Ser aag Lys atc Ile Gly 235 gca Al a ggc Gly gca Ala t cg 5cr ctc Leu 315 9gC :t c ,eu :tg ~eu gca Ala gcc Ala acc Thr 220 aac As n ggC Gi y tcc Scr gct Ala atc Ile 300 agc Ser atc Ile gac Asp gcg Ala ctt Leu ctc Leu 205 acc Th r gcc Al a ctq Leu gga Gly ttt Phe 285 ctg Le u atc Ile tat Tyr gcc Ala gcg Al a 365 ggc Gi y 190 gcg Ala tc Ser att Ile atc Ile atc Ile 270 ggt Gi y ttc Phe gaa Giu tat Tyr ctC Leu 350 ctc Leu gca Ala gtg Val1 ctg Leu ct t Leu gca Al a 255 gt g ValI ggc Gly ggC Gly act Thr gtg Val 335 ctc Leu kla tcC Se r tcc Ser atc Ile Ct C Leu 240 caa Gin Gly ga c Asp ac Thr tac Tyr 320 ttc Phe ceg Pro ctt Leu agc Ser ttg Leu gtg ValI 225 ccc Pro ttt Phe geg Ala tcc Ser gca Ala 305 a cg Thr a cg Thr cac Hi s 9gC Gly gga atc Gly Ile 195 ccg atg Pro Met 210 atg tcc Met Scr gga atc Gly Ile tta ggt Leu Gly ctg tgt Leu Cys 275 att cca Ile Pro 290 tat ggc Tyr Gly cca ctc Pro Leu tat ttg Tyr Leu ctt ggc Leu Gly 355 tcc gca Ser Ala ggc gat Gly Asp 180 aaa cac Lys His gca att Ala Ile gcg cgc Ala Arg ggc gcq Gly Ala 245 agg aaa Arg Lys 260 gcc ctc Ala Leu gtg tgg Vai Trp ctc tgC Leu Cys aac cga Asn Arg 325 gga ttc Gly Phe 340 gcc tc Ala Ser gta atc Val Ile 643 691 739 787 835 883 931 979 1027 1075 1123 1171 1219 370 cgc ggc Arg Gly 375 gaa gta caa atc aag Val Gin Ile Lys cgc Arg 380 ggg tat gtg gtt Gly Tyr Val Vai tagatttcta cctacqacct 1272 1275 WO 01/00804 WO 0100804PCTIIB00/00922 <210> 162 <211> 384 <212> PRT <213> Corynebacterium glutamicum <400> 162 Met Arg Ser Gly Asn Ala Asn Arg Val Phe Ile Gly Val Thr Ile Leo Leu Phe Thr Ala Gly Trp Leu Phe Val1 Val1 Pro Val1 Gly Pro 145 Pro Phe Ser Ile Gly Leu Leu Ser Val1 Val 130 Ile Phe Al a Gly Arg Ile Al a Ser Leu Ser 115 Thr Val1 Ala Leu Ile 195 Gl Tyr Asp Ala Leu 100 Al a Leu Thr Ile Gly 180 Lys IGin Ala Arg Leu Val Gi y Ala Ser Ser 165 Asp His I le Arg Ala Leu Leu Phe 70 Gly Gly Thr Gly Gly 150 Val1 Al a Glu T rp Ilie 230 Al a Ala IAsp IGly 55 GI y Asn Arg Ala Ile 135 Leu Al a Arg Arg Val 215 Asp Ile Ala~ ValI 40 Leu Ala Leu Phe Trp 120 Ile Gly Leu Ser Se r 20 0 ?he 3er Asn 25 Ser Leo Arg Se r Ile 105 Al a Leu Met Ser Th r 185 Met Ser Thr His Ser Pro Met Leu 90 Val Gly Thr Ala Leu 170 Pro Lys Cys Phe Phe Val Se r ValI 75 Leu Gly Arg Ala Se r 155 Ile Ser Lys Ile Gi y 235 Ala Leu Leu Val1 Ala Leu Leu Gl y 140 Thr Ala Ala Ala Thr 220 Asn Ser Val Leo Leu Phe Gly Arg 125 Phe Ser Val Leu Leu 205 Th r Al a Val Asn Al a Thr His Val1 110 Gl y Met Ile Val1 Gi y 190 Al a Se r Ile Ile Le u Gly Gly Gly Asp Gly Ala Met Ile Val1 175 Al a Val1 Leu Leu Ala Val Ala Gly Gly Gly Leu Se r Gly Thr 160 Gly Ser Ser Ile 1,eu 240 Gin Leo Pro Met Ala 210 la Phe Ser Ala Gly Leu 250 245 255 Phe Leo Gly Arg Lys Phe Ala Trp Giy Arg Gly Ser Gly Ile Val Gly WO 01/00804 PCTIIBOO/00922 260 265 270 Ala Leu Cys Ala Leu Ala Gly Phe Ala Leu Ala Ala Phe Gly Gly Asp 275 280 285 Ser Ile Pro Val Trp Leu Phe Vai Ile Ala Ser Ile Leu Phe Gly Thr 290 295 300 Ala Tyr Gly Leu Cys Leu Arg Giu Gly Leu Leu Ser Ile Giu Thr Tyr 305 310 315 320 Thr Pro Leu Asn Arg Arg Gly Thr Giy Ile Gly Ile Tyr Tyr Val Phe 325 330 335 Thr Tyr Leu Gly Phe Gly Leu Pro Vai Leu Leu Asp Ala Leu Leu Pro 340 345 350 His Leu Gly Ala Ser Ile Pro Leu Tyr Ala Leu Ala Ala Leu Ala Leu 355 360 365 Gly Ser Ala Val Ile Arg Gly Val Gin Ile Lys Arg Gly Tyr Val Val 370 375 380 <210> 163 <211> 1130 <212> DNA <213> Corynebacteriwn giutamicum <220> <221> 005 <222> (1107) <223> FRXA01922 <400> 163 ctg ctg ttt act qca gga tgg gca gcc aat cat ttc gcg tca gtg ttg 48 Leu Leu Phe Thr Ala Gly Trp Ala Ala Asn His Phe Ala Ser Val Leu 1 5 10 gtg ttg atc cgt gaa caa tta gac gta tca agc gtg ctg gtc aac ggc 96 Val Leu Ile Arq Giu Gin Leu Asp Val Ser Ser Val Leu Val Asn Gly 25 gct ttt ggt att tat gca ctg qqa ctt ctt cca agt ttg ctc gca ggc 144 Ala Phe Gly Ile Tyr A.1a Leu Gly Leu Leu Pro Ser Leu Leu Aia Gly 40 ggt gtg ctt gcc gac cgt ttt ggt gcc cgc atg gtg gta ctc acc gga 192 Giy Val Leu Ala Asp Arg Phe Giy Ala Arg Met Val Val Leu Thr Gly 55 ggt gta ctt tct gcg ctt gga aac ctt tct ctt tta gcg ttt cat gat 240 Gly Val Leu Ser Ala Leu Gly Asn Leu Ser Leu Leu Ala Phe His Asp 70 75 WO 01/00804 ggt cct. tcc ctc ctg gta gga cga ttc atc gtt ggt ctg ggc git gga Gly Pro Ser Leu Leu Val Gly Arg Phe Ile Val Gly Leu Giy Val Gly 90 t ta Leu ago Se r ggg Gly acg Thr 145 gga Gly tcc Ser tcc Se r ato Ile ctc Leu 225 caa Gin Gly gact As p' gt c ValI Gly cog Pro 130 ccc Pro ttt Phe agc Ser ttg Leu gtg Val 210 ccc Pro ttt Phe gcg ki a :cc ~er gtc Val gtg Val 115 att Ile ttt Phe gcg Ala gga Gly ocg Pro 195 atg Met gga Gi y tta Leu ctgI Leu att Ile 275 a gc Ser aca Thr gt g Val1 gc Ala ctt Leu atc Ile 180 atg Met t cC Ser atc Ile ggt :gt 60 :ca 'ro *Ala ttg *Leu aca Th r ata Ile Gly 165 aaa Lys gca Ala gog Ala ggC Gly agg Arg 245 gcc Ala gtg Val I1 Gi1 g0C Ala agt Sex a gc Ser 150 get Asp ec His att Ile 090 Arg gcg Al a 230 sa Lys ctc Leu :gg r p -acc ~Thr 99gc Gly gg *Gly 135 *gtt *Val g00 Ala gae Gi u t gg T rp etc Ile 215 gcg Al a ttc Phe gcg Ala ctt Leu gca Ala ati Ile 120 ttg Leu
C
Ala cgc Arg cga Arg gtg Val1 200 ge c Asp atc Ile gcg Ala 9gt Giy ttc Phe tgg TrF 105 at t Ile ggg Gly ctc Leu ago Ser agc Se r 185 ttc Phe t cc Ser 9CC Ala t gg Trp ttt Phe 265 gt t ValI goc )Ali ctC Let etc Met t og Ser acc Thr 170 atg Met a gc S er acc Thr tto Phe ggt GI y 250 gcg Ala atc Ile I gC Gly ac Thr gcg Ala ctg *Leu 155 ccg *Pro aaa Lys tgc Cys ttc Phe egc Ser 235 cgt Arg ctg Leu gcC Ala age Arg g00 Ala tog Se r 140 etc Ile a gc Ser a eq Lys atc Ile Gly 220 gce Ala ggc Gi y gce Al a t cg Ser ttg Leu ggt Gi y 125 aca Th r gog Al a gca Ala 900 Al a eco Th r 205 ac Asn ggc Gly tcc Ser gct Ala atc Ile 285 egc Arg 110 ttc Phe egc Ser gtg Val1 ctt.
Leu ctc Leu 190 acc Thr gcc Ale ctg Leu gga Gly ~ttt Phe 270 :tg ,eu gga Gly atg Met att.
Ile gt t Val1 990 Gly 175 gog Ala t CC Ser att Ile etc Ile atc Ile 255 ggt Gly ttc Phe gee Ala at q Met at t Ile gtg Val1 160 gca Ala gtg Val Ctg Leu Ct t Leu gca Al a 240 gtg Val1 9gC Gly Gly PCT/IBOO/00922 288 336 384 432 480 528 576 624 672 720 768 816 864 aco gca tat ggo cto tge otg cgc gaa ggc ctc otc ago etC gaa act Thr Ala 290 Tyr Gly Leu Cys Leu 295 Arg Glu Gly Leu Leu 300 Ser Ile Glu Thr tac Tyr 305 ttc Phe ccg Pro ctt Leu gtt Val1 WO 01/00804 acg cca ctc aac cga cgt ggc acc Thr Pro Leu Asn Arg Arg Gly Thr 310 acg tat ttg gga ttc ggg ctg cca Thr Tyr Leu Gly Phe Gly Leu Pro 325 cac ctt ggc gcc tcc att ccg ctg His Leu Gly Ala Ser Ile Pro Leu 340 345 ggc tcc gca gta atc cgc gqc gta Gly Ser Ala Val Ile Arg Gly Val 355 360 tagatttcta cctacgacct gaa atc ggc Ile Gly 315 ctt ctc Leu Leu gcg ctg Ala Leu atc aag Ile Lys atc tat Ile Tyr gac gc Asp Ala gcg gc9 Ala Ala 350 cgc ggg Arg Gly 365 PCT/IBOO/00922 tat gtg 960 Tyr Val 320 ctc ctc 1008 Leu Leu 335 ctc gcc 1056 Leu Ala tat gtg 1104 Tyr Val 1130 <210> 164 <211> 369 <212> PRT <213> Corynebacterium glutamicum <400> 164 Leu Leu Phe Thr Ala Gly Trp Ala Ala 1 5 Val Leu Ile Arg Glu Gin Leu Asp Val 25 Ala Phe Gly Ilie Tyr Ala Leu Gly Leu 40 Gly Val Leu Ala Asp Axrg Phe Gly Ala 55 Gly Val Leu Ser Ala Leu Gly Asn Leu 70 Gly Pro Ser Leu Leu Val Gly Arq Phe Leu Val Val Ser Ala Gly Thr Ala Trp 100 105 Ser Gly Val Thr Leu Ala Gly Ile Ile 115 120 Gly Pro Ile Val Thr Ser Gly Leu Gly 130 135 Thr Pro Phe Ala Ile Ser Val Ala Leu 145 150 Asn 10 Ser Leu Arg Ser Ile 90 Ala Leu Met Se r *His Ser Pro Met Leu 75 Val1 Gly Thr Ala Leu 155 Phe Val1 Ser Val1 Leu Gly Arg Al a Ser 140 Ile Ala Leu Leu Val1 Ala Lou Leu Gly 125 Th r Ala Ser Val Val Asn Leu Ala Leu Thr Phe His Gly Val Arg Gly 110 Phe Met Ser Ile Val Val Leu Gly Gly Gly Asp Gi y Al a Met Ile Val1 160 WO 01/00804 WO 0100804PCT/IBOO/00922 Gly Phe Ala Leu Asp Ala Arg Ser Thr Pro Ser Ala Leu Gly Ala Ser Ser Ile Leu 225 Gin Gly Asp Thr Tyr 305 Ser Leu Val 210 Pro Phe Al a Ser Ala 290 Thr Gly Pro 195 Met Gi y Leu Leu Ile 275 Tyr Pro Ile 180 Met Ser Ile Gly Cys 260 Pro Gi y Leu Lys His Ala Ile Ala Arg Gly Ala 230 Arg Lys 245 Ala Leu Val Trp Leu Cys Asn Arg 310 Gly Phe 325 Ala Ser Glu Trp I le 215 Ala Phe Ala Leu Leu 295 Arg Gly Ile Arg Val1 200 Asp Ile Al a Gly Phe 280 Arg Gly Leu Pro Ser 185 Phe Ser Ala Trp Phe 265 Val Glu Thr Pro Leu 345 170 -Met Lys Ser Cys Thr Phe Phe Ser 235 Gly Arg 250 Ala Leu Ile Ala Gly Leu Gly Ile 315 Val Leu 330 Tyr Ala Lys Ile Gly 220 Ala Gi y Ala Ser Leu 300 Gly Leu Leu 175 Ala Thr 205 Asn Gly Ser Al a Ile 285 Ser Ile Asp Ala Leu 190 Thr Ala Leu Gly Phe 270 Leu Ile Tyr Al a Ala 350 Ala Ser Ile Ile Ile 255 Gly Phe Glu Tyr Leu 335 Leu Val1 Leu Leu Ala 240 Val1 Gly Gly Thr Val1 320 Leu Al a Phe Thr Tyr Leu Pro His Leu Gly 340 Leu Gly Ser Ala Val Ile Arg Gly 360 Val Gin Ile Lys Gly Tyr Val <210> 165 <211> 362 <212> DNA <213> Corynebacterium giutamicun <2 <221> CDS <222> (339) <223> RXA02060 <400> 165 gaa ttt 9cc cgc att ttg aag cca aag gga cag gte atc gtg ctt ace 48 Glu Phe Ala Arg Ile Leu Lys Pro Lys Gly Gln Val Ile Val Leu Thr 1 5 10 gca Ala gat Asp cac His ctg Le u cg c Arg ga a Giu atc Ile WO 01/00804 gat acc ggc cac ttg gct gag Asp Thr Gly [-is Leu Ala Giu gtg gag gcc ggc aaa gtt gat Val Giu Ala Gly Lys Val Asp ctc aag cca gtt ggc gaa aga Leu Lys Pro Val Gly Glu Arg gat caa aaa tcc att gca tct Asp Gin Lys Ser Ile Ala Ser cac att aag cct gag gct ttq His Ile Lys Pro Glu Ala Leu caa atg aag gtt aca gcc cgg Gin Met Lys Val Thr Ala Arg 100 taactcttat ctcactgggc ctt ct t Leu 25 cgc Arg gac Asp cag Gin gcg Al a gcc Al a 105 ggc Gly gcg Ala ga a Giu cc t Pro gct Ala ctg Leu 110 PCT/IBOO/00922 96 144 192 240 288 336 <210> 166 <211> 113 <212> PRT <213> Corynebacteriin giutamicum <400> 166 Giu Phe Ala Arg Ile Leu Lys Pro Lys 1 5 Ala Asp Thr Gly His Leu Ala Glu Leu 25 Asp Val Giu Ala Gly Lys Val Asp Arg 40 His Leu Lys Pro Val Gly Giu Arg Asp Leu Asp Gin Lys Ser Ile Ala Ser Gin 70 Arg His Ile Lys Pro Giu Ala Leu Ala Giu Gin Met Lys Val Thr Ala Arg'Ala 100 105 Ile Val Leu Gly Gin Ala Phe Glu Ser Pro Ala Aia Arg Leu 110 Leu Ile Ala Met Ser Leu Glu Thr Ile Gly Leu Al a Pro Arg WO 01/00804 WO 0100804PCTIBOO/00922 <210> 167 <211> 1395 <212> DNA <213> Corynebacterium qiutamicum <220> <221> CDS <222> (101) (1372) <223> RXN01936 <400> 167 gcgcggtgae aceacagccg ttgtcagcgg cgcttggtct ctaacaaata ggcccaacaa agaggtctaa gctctacctq gtggaggatc geegaggtta gtg agt ttc cga gat att ttc Ile Phe tgg ett Trp Leu gcc gtt Ala Val ggc ttg Gly Leu tat ggt Tyr Gly tgc acc Cys Thr ace att Thr Ile tta cag Leu Gin get Ala ggc Gly ceg Pro ace Thr gga Giy acg Thr t ta Leu cag Gin 120 ga c Asp aat Asn gt g Val1 ggg Gly tee Ser at c Ile Gly 105 gca Al a ace Thr gt t Val1 eag Gin ctt Leu att Ile Gi y aat As n ttt Phe a ga Arg gee Al a att Ile ttt Phe 9gg Ala 75 atg Met gag Gi u ttc Phe ccq Pro a cc Thr tac Tyr ggc Gly 60 ga t Asp tgt Cys aat Asn gcg Ala ctg Leu gte Val1 eaa Gin 45 ct t Leu get Ala gte Val1 att Ilie gtg Vali 125 aa a Lys att Ilie atg Met att Ile ttt Phe ace Thr t gg Trp 110 aat Asn gaa Gi u ggt Gly act Thr ct Pro ga t Asp act Th r etc Leu caa Gin ceg Pro gc Aia ggg Gly ttg Leu aaa Lys 80 gee Ala ctg Leu c Pro Val 1 gee Ala eaa Gin tee Ser gt t Val1 ege Arg ggt Gly tta Leu ace Thr Ser Phe Arg tte Phe tta Leu tee Ser att Ile ate Ile ttt Phe ata Ile ega Arg 130 gea Ala Asp etc Leu gtt Val gtg Val ct t Leu ate Ile ctg Leu tet Ser ate Ile 115 163 211 259 307 355 403 451 499 547 ctt cga agt att ttg ceg att gat eaa tta geg teg aea tea etg Thr Ser Leu Leu Arg 135 Ser Ilie Leu Pro Ile 140 Asp Gin Leu Ala WO 01/00804 aat atg ctg ctc Asn Met Leu Leu PCTIBOO/00922 595 atg cag acc ggc gca atc gtt ggc ccg ctg atc gca Met Gin Thr Gly Ala Ile Val Gly Pro Leu Ile Ala 155 160 165 150 ggt Gly gtt Val atc Ile ga t Asp gtg Val1 230 ccc Pro at g Met ggC Gly gtt Val1 gtg Val 310 ttc Phe gca Ala qgC gcg Ala gt c Val1 aag Lys ggc Gi y 215 cig Leu gag Gi u ctg Leu gig Val1 tat Tyr 295 gca Ala atc Ile gt Val1 cga ttg Le u tc Ser cca Pro 200 ctg Leu ga t Asp at c Ile gcg Ala cig Leu 280 t gg Trp att Ile atc Ile cga Arg2 etc att I le etc I le 165 tcc Ser ag Lys ct t Leu gca Ala to Phe 265 t ct Ser tgC Cys gt t Val1 atg Met aac Isn 345 :aa *ccg Pro 170 *aic Ile Gly tat Tyr atc Ile gaa Glu 250 a ig Met ggt Gi y atc Ilie gtc Val1 atg Met 330 got Ala ggt ct.
Le~ cc( PrC eec Lys ttg Leiu gc Ala 235 gig Val1 tac Tyr tgg Trp aic Ilie agc Ser 315 gic Val att.
Ilie ;t g ;atc i Ile ace Thr gtg Val got IAla 220 atg Met aac As n toe Se r gt g Val gcc Ala 300
CCC
Pro att Ile ttg LeuC tgg a Trp I ggt Gi y ctq Leu atg Met 205 ggC Gly at t Ile tc Phe tcc Se r gcc Ala 285 t gg Trp 9gC ggt 31 y :ag ;ln Ito le tc Phe tgg Trp 190 aag Lys caa Gin tc Phe ggt Gly atg Met 270 c99 Arg gg C Gly gcg Ala ggc Gly cag Gin 350 atc Ile 9g9 Gi y 175 gct Al a gct Al a ccc Pro 9gC Gly ggg Gly 255 got Ala att Ile gca Al a gig Val aig Met 335 tct Ser gtc Val tgg Trp ga Val1 ggt Giy gtg Val1 atg Met 240 gg t Gly gtt ValI ago Ser g cc Ala act Th r 320 gct Ala got Ala gtg Val ctg Letu t gg Trp ttc Phe ttg Le u 225 cca Pro gao Asp ggC Gly cgo Arg gitt Val1 305 gcg Al a gac Asp gcg Ala qg Val1 tat ITyr tca pSer gcc Al a 210 tig Leu cgt Arg gc Ala g ca Ala cag Gin 290 gct Al a tgg Trp atg Met gee Giu ggt Gly 370 to Phe ct g Leu 195 agt Ser atg Met gcg Ala ggt Gly gt t Val1 275 gg t Gi y tg Leu gog Ala t tc Phe cat His 355 gga ily ct Leu 180 cct Pro gig Vali gtg Val1 ctt Leu gca Ala 260 ct Leu gt t Val1 ggt Gly tgg Trp ago Ser 340 gig ValI oct Pro get Asp t cg Ser gg ValI atg Met tac Tyr 245 aog Th r ggc Gi y gca Ala ggt Giy atg Met 325 i cg Ser cag Gin cgt Arg 643 691 739 787 835 883 931 979 1027 1075 1123 1171 1219 1267 Gly Arg Ile Gin Gly Val 360 365 tta gct gac gtc ott ceo ggt tgg gcc gct gag ccc cic ggc gca ggt Leu tgg Trp 390 t gt Cys acc Thr WO 01/00804 Ala Asp Val Leu His Gly Trp Ala Ala Giu Pro Leu Gly Ala Gly 375 380 385 acg gta tta tgg ggc gga gta qcg gtq gtt gta ctc act gca att Thr Val Leu Trp Gly Gly Val Ala Val Val Vai Leu Thr Ala Ile 395 400 405 atq gtg qcg gtg cct aaa ttc tgg aaa tac gag aaa cca aaa att Met Val Ala Val Pro Lys Phe Trp Lys Tyr Glu Lys Pro Lys Ile 410 415 420 ggc atc taaatactta tccatgccca ttt Gly Ilie PCT/IBOO/00922 1315 1363 1395 <210> 168 <211> 424 <212> PRT <213> Corynebacterium glutamicum <400> 168 Val Ser Phe Arg 1 Ala Gin Ser Val1 Arg Gly Leu Thr Phe Leu Ser Ile Ile Phe Ilie Arg Lys Thr Gi y Phe Val Trp Asn 115 Thr Arg Val1 Tyr Gly Leu Val1 100 Phe Ala Asp Ile Phe 5 Leu Trp, Leu Val Ala Val Val Gly Leu 55 Leu Tyr Gly 70 Ile Cys Thr Leu Thr Ile Ser Leu Gin Ile Leu Arq 135 Leu Asn Met 150 Ala Asp Thr Arg Pro Leu Lys Giu Pro 10 Gi y Pro 40 Thr Gly Thr Leu Gin 120 Ser Leu Asn 25 Val Gly Ser Ile Gly 105 Ala Ile Leu Val Gin Leu Ile Gi y 90 Asn Phe Leu Met Pro Ala Ile Phe Al a 75 Met Glu Phe Pro Gin 155 Leu Thr Val Tyr Gin Gly Leu Asp Ala Cys Val Asn Ile Ala Val 125 Ile Asp 140 Thr Gly Ile Gly Ilie Met Ile Phe Thr Trp 110 Asn Gin Al a Phe Gly Thr Pro Asp Thr Leu Gin Leu Ile Gi y 175 Ala Gi y Leu Lys Ala Leu Pro Ala Val 160 T rp 130 Ser Ala Thr Ser 145 Gly Pro Leu Ilie Ala Gly Ala Leu Ile 165 Leu Tyr Phe 18018 Val Val Ser Ile 185 Ile Pro Thr Leu Trp Ala Val 190 WO 01/00804 Trp Ser Leu Pro 195 PCTIBOO/00922 Ser Ile Lys Pro Ser Gly Lys Val Met Lys Ala Gly 200 205 Phe Leu 225 Pro Asp Gly Arg Val 305 Al a Asp Ala Val Pro 385 Val1 Ala 210 Leu Arg Ala Al a Gin 290 Al a Trp Met Glu cay 370 Leu Leu Ser Met Al a GI y Val1 275 Gly Leu Ala Phe His 355 Gly Gly Thr Val Val Asp Gly 215 *Val Met Val Leu 230 *Leu Tyr Pro Glu 245 Ala Thr Met Leu 260 Leu Gly Gly Val Val Ala Val Tyr 295 Gly Gly Val Ala 310 Trp Met Phe Ile 325 Ser Ser Ala Val 340 Val Gin Gly Arg Pro Arg Leu Ala 375 Ala Gly Trp Thr 390 Ala Ile Cys Met Leu Lys Tyr Leu Asp Leu Ile Ile Ala Giu 250 Ala Phe Met 265 Leu Ser Gly 280 Trp Cys Ile Ile Val Val Ile Met Met 330 Arg Asn Ala 345 Ile Gln Gly 360 Asp Val Leu V~al Leu Trp lal Ala Val 410 Al a 235 Val Tyr Trp Ile Ser 315 Val Ile Val1 His Gly4 395 Pro Ala 220 Met As n Ser Val1 Ala 300 Pro Ile Leu Trp Gly 380 Gly Lys GI y Ile Phe S er Ala 285 Trp Gi y Gi y Gin Ile 365 Trp Val1 Phe Gin Phe Gly Met 270 Arg Gly Ala Giy Gin 350 Ile Ala Al a Trp Pro Gly Gly 255 Ala Ile Al a Vai Met 335 Ser Val1 Ala ValI Lys 415 Val1 Met 240 Gly Val1 Ser Ala Thr 320 Al a Al a Val1 Glu Val 400 Tyr 405 Giu Lys Pro Lys 420 Ile Thr Gly Ile <210> 169 <211> 945 <212> DNA <213> Corynebacterium glutamicum <2 <221> CDS <222> (101)..(922) <223> FRXA01936 WO 01/00804 <400> 169 tttacagcag gcatttttcg cggtgaatca accaccega PCT/IBOO/00922 acggcgatcc ttcgaagtat tttgecgatt gatcaataag cgtcggcaae atcactgaat atg ctg etc atg cag Met Leu Leu Met Gin ace Thr ate Ile aca Thr gtg Vali get Ala at g Met aac Asn t ca Ser gtg Val gee Ala 150 ccc Pro qge Gly ggt Gly ctg Leu atg Met ggc Gly att Ile t te Phe t cc Ser gce Ala 135 t gg rrp Gly gca Ala ttc Phe tgg Trp aag Lys ca a Gin ttc Phe ggt Gly atg Met 120 Cgg Arg gge Giy geg Ala atc IlE ggj Gi get Ala gct Ala ccc Pro ggC Gi y Gly 105 gct Al a at t Ile gca Ala gtg Val -gtt Val tgg Trp *gta Val ggt Gly gtg Val1 atg Met ggt Gly gtt Val1 age Ser gc Ala act Thr2 170 gg G1 ct Let t gc TrF ttc Phe ttg Le u 75 cca Pro gac Asp ggc Gly ege Arg gt t Val1 155 gcg kla ccg yr Pro ;tat STyr tea Ser *gcc *Ala 60 Ittg Leu cgt Arg gcc Ala gca Ala cag Gin 140 getI Ala tgg Trp atg t Met P etc Leu ttC Phe ct g Leu 45 agt Ser atg Met gcg Ala ggt Gly gtt Val1 125 ggt Gly ttg eu ;cg la :tc ate I le ctt Leu cet Pro gtg Val1 qtg Val ctt Leu gca Ala 110 ctt Leu gtt Val ggt Gly tgg Trp age t Ser S 190 gca Ala gat Asp t cg Ser gt g Val1 at g Met tac Tyr 95 acg Thr gge Gly gca Al a ggt 31y Itg let L75 :eg er ggt Gly gtt Val atc Ile ga t Asp gtg Val1 80 ccc Pro atg Met ggc Gly gt t Val1 gtg Val 160 ttc Phe gca Ala gec Ala gt c ValI aag Lys ggc Gi y 65 ctg Leu gag Giu etg Leu ge g Val1 tat Tyr 145 ga Ala ate Ile Itt la I ttg Leu tcc *Ser cea *Pro 50 ctg Leu gat Asp ate Ile gcg Ala ct g Leu 130 tgg Trp att Ile ate Ile cga Arg att Ile atc Ile 35 tee Ser aag Lys ct t Le u gca Al a tte Phe 115 tet Ser tge Cys gt t Val1 atg M1et sac As n 195 ceg Pro 20 ate Ile Gly tat Tyr ate Ile gaa Giu 100 atg Met ggt Gi y ate Ile gte Val1 atg Met 180 get Ala ct g Leu ec Pro aag Lys ttg Leu gc Al a gtg Val t ac Tyr t gg Trp ate Ile age Ser 165 gte Val att Ile 115 163 211 259 307 355 403 451 499 547 595 643 691 att ggt gge atg get gac Ile Giy Gly Met Ala Asp 185 ttg cag cag tet get gcg gaa cat gtg Leu Gin Gin Ser Ala Ala Glu His Val eag ggc ega ate eaa ggt gtg Gin Gly Arg Ile Gin Gly Val WO 01/00804 200 205 tgg atc ate gtc gtg gtg ggt gga cct cgt tta gct Trp Ile Ile Val Val Val Gly Gly Pro Arg Leu Ala 215 220 225 qgt tgg gcc get gag ccc ctc ggc gca ggt tgg acg Gly Trp Ala Ala Giu Pro Leu Gly Ala Gly Trp Thr 230 235 240 gga gta gcg gtg gtt gta etc act gca att tgt atg Gly Val Ala Val Val Val Leu Thr Ala Ile Cys Met 250 255 aaa ttc tgg aaa tac gag aaa cca aaa att acc ggc Lys Phe Trp Lys Tyr Giu Lys Pro Lys Ile Thr Gly 265 270 tccatgccca ttt <210> 170 <211> 274 <212> PRT <213> Corynebacterium glutamicum PCTIIBOO/00922 210 gac gtc ctt cac Asp Val Leu His gta tta tgg ggc Val Leu Trp Gly 245 gtg gcg gtg cct Val Ala Val Pro 260 atc taaatactta Ile <400> 170 Met Leu Leu Met Gin Thr Gly Ala Ile Val Gly Pro Leu Ile Ala Gly 1 Ala Leu Val Ser Lys Pro Gly Leu Leu Asp Glu Ile Leu Ala Val Leu 130 Tyr Trp 145 Ile Ile Ser Lys Leu Ala Phe 115 Ser Cys Pro Ile Gly Tyr Ile Glu 100 Met Gly Ile 5 Leu Pro Lys Leu Al a ValI Tyr T rp Ile Ile Thr Val1 Al a 70 Met Asn Ser Val Ala 150 Gly Leu Met 55 Gly Ile Phe Se r Ala 135 Trp Phe Trp 40 Lys Gin Phe Gly Met 120 Arg Giy Gly 25 Ala Ala Pro Gly Gly 105 Al a Ile Ala T rp Val Gly Val1 Met Gly ValI Ser Al a Leu Trp Phe Leu 75 Pro Asp Gly Arg Val 155 Tyr Phe Ser Leu Ala Ser Leu Met Arg Ala Ala Gly Ala Val 125 Gin Gly 140 Ala Leu Leu Pro Val Val1 Leu Ala 110 Leu Val Gly Val Ile Asp Val1 Pro Met Gly Val Val1 160 Ala Ile Val1 Arg Ala 225 Thr Met Gly WO 01/00804 Ile Val Val Ile Met Met 180 Arg Asn Ala 195 Ile Gin Giy 210 Asp Val Leu Val Leu Trp Val Ala Val 260 Ile Val Met 185 Ser Val Ala Val1 Lys 265 PCT/IBOO/00922 <210> 171 <211> 549 <212> DNA <213> Corynebacteriun glutamicun <220> <221> CDS <222> (526) <223> FRXA01937 <400> 171 gcgcggtgac accacagccg ttgtcagcgg cgcttggtct ctaacaaata ggcccaacaa agaggtctaa gctctacctg att Ile t gg Trp gcc Ala 99C Gi y gac acc Asp Thr aat gtt Asn Val gtg cag Val Gin ggg ctt Gly Leu ccg ctg Pro Leu acc gtc Thr Val tac caa Tyr Gin ggc ctt Gly Leu gtggaggatc gccgaggtta gtg agt ttc cga gat Val Ser Phe Arg Asp 1 gcc ttc aaa cgc ctc Ala Phe Lys Arg Leu caa tta act gtt gtt Gin Leu Thr Val Val tcc tcc ggc tat gtg Ser Ser Gly Tyr Val gtt att ttt ggc Ctt Val Ile Phe Gly Leu WO 01/00804 tat ggt gga tee att gcg gat gct ttt Tyr Gly Gly Ser Ile Ala Asp Ala Phe 75 tgc acc acg ate ggc atg tgt gtc ace Cys Thr Thr Ile Gly Met Cys Val Thr acc att tta ggc aat gag aat att tgg Thr Ile Leu Gly Asn Glu Asn Ile Trp 105 110 tta cag cag gca ttt ttc gcg gtg aat Leu Gin Gin Ala Phe Phe Ala Val Asn 120 125 ctt ega agt att ttg eeg att gat eaa Leu Arg Ser Ile Leu Pro Ilie Asp Gin 135 140 ga a <210> 172 <21i> 142 <212> PRT <213> Corynebaeteriun giutamicun <400> 172 Val Ser Phe Axg Asp Ilie Phe Ala Asp 1 5 Ala Phe Lys Arg Leu Trp Leu Gly Asn 25 Gin Leu Thr Val Val Ala Val Pro Val 40 Ser Ser Gly Tyr Val Gly Leu Thr Gly 55 Val Ile Phe Gly Leu Tyr Gly Gly Ser 70 Arg Ile Val Leu Ile Cys Thr Thr Ile Gly Phe Trp Val Leu Thr Ile Leu Gly 100 105 Leu Ile Asn Phe Ser Leu Gin Gin Ala 115 120 Thr Arg Thr Ala Ile Leu Arg Ser Ile 1 130 135 PCT/IBOO/00922 gat aaa ege ate gtg etg ate 355 Asp Lys Arg Ile Val Leu Ile 80 act gee ggt ttt tgg gtg ctg 403 Thr Ala Gly Phe Trp Vai Leu 95 *100 etc ctg tta ata aac ttt tet 451 Leu Leu Leu Ile Asn Phe Ser 115 caa. eec ace ega acg geg ate 499 Gin Pro Thr Arg Thr Ala Ile 130 taagegtcgg caacatcaet 546 Arg Pro Ala Thr Ile Tyr Phe Gly Aia Asp Met Cys Giu Asn Phe Ala Pro Ile 140 Leu Val Gin Leu Ala Val1 Ile Val 125 Asp Lys Ile Met Ile Phe Tb r Trp 110 Asn Gin Giu Gly Thr Pro Asp Th r Leu Gin WO 01/00804 <210> 173 <211> 1242 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> (1219) <223> RXN01010 <400> 173 gtqccaaagc qtttcctgta aaacgcataa ccccgaatac aaaagatctg gcagggggtt taggcataga ttaggaactt PCTIBOO/00922 cccctgtttc cagatccaaa.
atg aag aaa ctg caa Met Lys Lys Leu Gin atc Met gct Ala gtc Val1 acc Th r aag Lys cic Leu att Ile cg t Arg gct ccg Pro *cta *Leu agc Se r atg Met gtg Val1 cta Leu gg t Gi y gag Giu gcg gcc Ala t ca cag Gin a tg Met gtg Val1 gtt Val etc Ile ctt Leu 120 atg att Ile gtg Val gca Al a t tg Leu ca g Gin aca Th r gct Ala 105 gtt Val caa tt~ Let gtC Val Ala ttt Phe gcg Al a cca Pro aat Asn ccg Pro t ca Igtc IVal ttg Leu Ictg Leu tcg Se r gct Ala 75 t cg Ser gca Al a ccg Pro ctc g W
GI~
ccq Prc acc Th r ggg Ci y 60 tat Tyr tgg Trp ttt Phe cgt PArg 9gC ggc SGly gaa Glu atg Met 45 cgc Arg att Ile ggg Gly acc Thr tct Ser 125 atg Met ttt Phe ttt Phe 30 acc Thr atc Ile gt C Val1 ctg Leu act Thr 110 ttg Leu ttg gtg Val1 15 gca Ala gca Al a acc Thr aca Thr ttt Phe 95 ccg Pro ggt Gly L cq ggg Gly gac Asp tac Tyr age Arg ctg Leu 80 atg Met gtg Val aeg Lys gcg ccg.
Pro acc: Thr ttg Leu aag Lys cc a Pro gct Al a ctg Leu gca Ala cca.
ttt Phe ttt Phe ttg Leu etc Ile ctt Leu gcg Ala caa Gin ttg Leu 130 ct g act Thr gat Asp ccc Pro cat His gcg Ala tat T yr att Ile 115 ggc Gly etc ggc cee Gly Gin etc agt Ile Ser ttt gcC Phe Ala ccg cat Pro His ctg ttg Leu Leu gcc acg Ala Thr 100 atg ttg Met Leu acc tat Thr Tyr gca ggt Ala Gly 163 211 259 307 355 403 451 499 547 Ala Ala Met Gin Ser Leu 135 Gly 140 Leu Ser Ala Pro Leu Ile 145 tct tcg gtg gtq Ser Ser Val Val tgg egg ttg acc Trp Arg Leu Thr ctg gtc act gce Leu Val Thr Ala WO 01/00804 W00110804PCT/IBOO/00922 gcg tea ctg itt att tic Ala Ser tea gca Ser Ala ate ate Ile Ile ait gga Ile Gly 215 gct gca Ala Ala 230 ttt gcc Phe Ala gcg gtg Ala Val ctg ccg Leu Pro gca gta Ala Val 295 atc gga Ile Gly 310 cga tie Arg Phe atg ggc Met Gly te gtt Phe Val Leu t cg Se r cac His 200 ttc Phe gcg Ala icc Ser etc Leu ate Ile 280 gca Ala age Ser tie Phe ate Ile gee Al a Ph e aac Lys 185 atg Met atg Met cgt Arg cge Arg ati Ile 265 gca Ala gca Ala ccc Pro gga Gly ggC Gi y 345 atc Ile 170 caa Gin gtt ValI aca Thr ggt Gly aag Lys 250 gt c Val1 ceg Pro gca Ala ggt Gly tea Ser 330 tcg Ser gee Leu aac Asr icc Ser tcg Ser ttg Leu 235 att Ile aqt Ser t gg Trp caa Gin gga Gi y 315 9cg Gly cag gig Val *gt Val ggc Gly Icig *Leu 220 gig Val 4gc Gly get Al a ate Ile gga Gi y 300 t ca Ser gca Ala geg Ala tgg gcg cga etc ccc gtt git cca cca cca Al a agt Se r ttt Phe 205 eac His gi c Val1 ga t Asp gt c Val1 tt Ile 285 at c Ile t cg S er gca AIla ttt Phe c Leu 365 Arg gge Giy 190 gig Val gt Val1 atg Met tig Leu ate Ile 270 gig Val caa Gin ctg Leu cca Pro tgg Trp 350 aac Asn Leu 175 a ag Lys gtg Val ggc Gi y igi Cys gca Ala 255 ggt Gly gig Val gca Ala ct Leu gt g Val1 335 gte Val ceg Pro Pro gig Val1 Gi y gag Giu ggt Gly 240 gac Asp ace Thr gee Ala ace Thr t ci Se r 320 a ca Thr age Ser cag Gin Val1 cag Gin atc Ile caa Gin 225 ggc Gi y aaa Lys atc Ile gi a Val1 gi c Val 305 acc Thr tc Phe gcg Al a egg Arg Val t gg T rp ggc Gly 210 tic Phe ctg Leu ttt Phe gca Ala ci g Leu 290 aac Asn gig Val cii Leu gi a ValI gig Val1 Pro gga Gi y 195 ate Ile gqa GI y gct Aila ggi Giy etc Leu 275 tg Trp itg Leu cag Gin cci Pro geg Ala 355 gag Glu Pro 180 ceg Pro ate Ile ct Leu g eg Aia gig Val 260 gca Ala gcc Al a get Al a get Ala ate Ile 340 cig Leu cgg Arg Pro ace Thr ggC Gly gat Asp tc Phe 245 cge Arg et g Leu tte Phe gte Val1 tte Phe 325 tat Tyr tie Phe gge Gly 643 691 739 787 835 883 931 979 1027 1075 1123 1171 1219 Ile Ala Gin Trp 360 igagggagae gtegagaage gte 1242 <210> 174 WO 01/00804 <211> 373 <212> PRT <213> Corynebacterium glutamicum PCT/IBOO/00922 <400> 174 Met Lys Lys Leu Gin Met Pro Ala Ile Leu Val Gly Gly Phe Val Gly 1 Pro Phe Thr Gl Thr Phe Asp Ile Leu Leu Pro Phe Lys Ilie His Pro Pro Leu Ala Leu Ala Ala Tyr Ala 100 Leu Gin Ile Met 115 Ala Leu Gly Thr 130 Pro Leu Ile Ala 145 Leu Val Thr Ala Val Val Pro Pro 180 Gin Trp Gly Pro 195 Ile Giy Ile Ile 210 Gin Phe Gly Leu 225 Giy Leu Ala Ala Lys Phe Gly Val 260 5 Gin Ala Leu *Ser Val Ser *Ala Thr Met 55 *His Lys Val 70 Leu Leu Leu Thr Ile Gly Leu Arg Giu Tyr Ala Ala 135 Gly Vai Ser 150 Ala Ala Ser 165 Pro Ser Ala Thr Ile Ile Gly Ile Gly 215 Asp Ala Ala 230 Phe Phe Ala 245 Arg Ala Val 10 Sex Gir 40 Met Vai Val Ile Leu 120 Met Ser Leu Ser His 200 Phe kla.
3e r .,eu Val 25 Ala Leu Gin Thr Ala 105 ValI Gin Val1 Phe Lys 185 Met Met Arg Arg Ile Val Al a Phe Ala Pro 90 Asn Pro Ser Val1 Ile 170 Gin Val1 Thr Gly Lys 250 Val1 Leu Leu Se r Al a 75 Se r Ala Pro Leu Ser 155 Leu Asn Ser Ser Leu 235 Ile Ser Pro Thr Gly Tyr Trp Phe Arg Gly 140 Trp Val1 Val1 Gly Leu 220 Val Gly Ala Glu Met Arg Ile Gly Thr Ser 125 Met Arg Ala Ser Phe 205 His Val1 Asp ValI Phe Thr Ile Val1 Leu Thr 110 Leu Leu Leu Arg Gly 190 Val Val Met Leu Ile Ala Al a Thr Thr Phe Pro Gly Ser Th r Leu 175 Lys Val1 Gi y Cys Al a 255 Gly Asp Tyr Arg Leu Met ValI Lys Ala Phe 160 Pro Val Giy Glu Gly 240 Asp Thr 265 270 Ile Ala Leu Ala Leo Leo Pro Ile Ala Pro Trp Ile Ile Val Val Ala WO 01/00804 275 280 Val Leu Trp Ala Phe Ala Val Ala Ala Ala Gin 290 295 Val Asn Leu Ala Val Ile Gly Ser Pro Gly Gly 305 310 315 Thr Val Gin Ala Phe Arg Phe Phe Gly Ser Ala 325 330 Phe Leu Pro Ile Tyr Met Gly Ilie Gly Ser Gly 340 345 Ala Val Ala Leu Phe Phe Val Ala Ilie Ala Gin 355 360 Arg Val Giu Arg Gly 370 <210> 175 <211> 871 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> (101)..4871) <223> FRXA01010 <400> 175 gtgecaaage gtttcetgta aaaegcataa eeeegaatae aaaagatctg gcagggggtt taggeataga ttaggaactt PCT/IBOO/00922 Gly 300 Ser Ala Ala T rp 285 Ile Gin Ala Thr Ser Leu Leu Ser 320 Ala Pro Val Thr 335 Phe Trp Val Ser 350 Leu Asn Pro Gin 365 atg ccg Met Pro get eta Ala Leu gtc agc Val Ser acc atg Thr Met aag gtg Lys Vai gee att Ala Ile tea gtg Ser Val cag gca Gin Ala atg ttg Met Leu gtg cag Val Gin ttg gte Leu Val gte ttg Vai Leo geg etg Ala Leo ttt tcg Phe Set gcg get Ala Ala 75 gge ttt Gly Phe gaa ttt Giu Phe 30 atg ace Met Thr 45 egc ate Arg Ile att gte Ile Val gtg ggg Val Gly 15 gca gac Ala Asp gca tac Ala Tyr ace aga Thr Arg aca etg Thr Leu 80 ceeetgtttc eagateeaaa atg aag aaa ctg caa Met Lys Lys Leu Gin 1 ceg ttt act gge caa Pro Phe Thr Gly Gin ace ttt gat ate agt Thr Phe Asp Ile Ser ttg ttg cec ttt gee Leo Leo Pro Phe Ala aag ate eat ccg cat Lys Ile His Pro His cca ctt geg ctg ttg Pro Leu Ala Leu Leo 115 163 211 259 307 355 WO 01/00804 ctc Leu at t Ile cg t Arg gct Ala gtg Val 150 gcg Ala t ca Ser atc Ile att Ile act Thr 230 cta gtt Leu Val ggt atc Gly Ile gag ctt Giu Leu 120 gcg atg Ala Met 135 tct tcg Ser Ser tca ctg Ser Leu gca ttg Ala Leu atc cac Ile His 200 gga ttc Gly Pne 215 gca gcg Ala Ala aca Thr gct Ala 105 gtt Val1 caa Gln gt g ValI ttt Phe aag Lys 185 atg Met at g Met cgt Arg cca Pro aat As n ccg Pro t ca Se r gtg Val att Ile 170 caa Gin gt t ValI aca Thr ggt Gly tcg tgg ggg Ser Trp Gly ctg ttt atg gct gcg tat gcc acg Leu Phe Met Ala Ala Tyr Ala Thr 95 100 gca Ala ccg Pro ctc Leu tcg Ser 155 ttg Leu aac Asn t cc Ser t cg Ser ttg Leu 235 ttt Phe cgt Arg ggc Gly 140 tgg Trp gtg ValI gtt Val ggc Gly ctg Leu 220 gt g Val1 acc Thr tct Se r 125 atg Met agg Arg gcg Ala agt Ser ttt Phe 205 ca c His gt C ValI act Thr 110 ttg Leu ttg Leu ttg Leu.
cga Arg ggC Gly 190 gtg ValI gt t ValI a tg Met ccg Pro ggt Gly t cg Ser acc Thr ct C Leu 175 aag Lys gtg Val Giy tgt Cys gtg Val aag Lys gcg Al a ttc Phe 160
CCC
Pro gtg Val ggc Gly gag Giu ggt Gly 240 caa Gin t tg Leu 130 ctg Leu gtc Val gtt Vai tgg Trp ggc Gly 210 ttc Phe cgg Arg ttg Leu tat Tyr gg t Giy gca Ala 165 cca Pro acc Thr 9gC Gly aat Asn ttC Phe 245 PCT/IBOO/00922 403 451 499 547 595 643 691 739 787 835 ttt gcc tcc cgc aag ata ggc gat ttg gca gac aaa Phe Ala Ser Arg Lys Ile Gly Asp Leu Ala Asp Lys 250 255 <210> 176 <211> 257 <212> PRT <213> Corynebacterium glutamicum <400> 176 Met Lys Lys Leu Gin Met Pro Ala Ile Leu Val Gly Giy Phe Val Gly 1 5 10 Pro Phe Thr Gly Gln Ala Leu Ser Val Val Leu Pro Giu Phe Ala Asp 25 wo 01/00804 WO 0100804PCT/IBOO/00922 Thr Phe Asp Ilie Leu Leu Pro Phe Lys Ile His Pro Pro Leu Ala Leu Ala Ala Tyr Ala 100 Leu Gin Ile Met 115 Ala Leu Gly Thr 130 Pro Leu Ile Ala 145 Leu Val Thr Ala Val Val Pro Pro 180 Gin Trp Gly Pro 195 Ile Gly Ile Ile 210 Gin Phe Giy Leu 225 Gly Arg Ala Ala Lys Ser Val Ser Gin Ala Ala Leu Thr Met Thr Ala Tyr 40 Ala His Leu Thr Le u Tyr Gly Ala 165 Pro Thr Gly As n Phe 245 Thr Lys 70 Leu Ile Arg Ala Val1 150 Al a Ser Ile Ile Thr 230 Phe Met 55 Val1 Leu Giy Glu Ala 135 Ser Ser Ala Ile Gly 215 Ala Ala Met Val1 ValI Ile Leu 120 Met Se r Leu Leu His 200 Phe Ala Ser Leu Gin Thr Ala 105 Val1 Gin Val1 Phe Lys 185 Met Met Arq Arg Phe Ala Pro 90 Asn Pro Se r ValI Ile 170 Gin Val1 Thr Gly Lys 250 Ser Giy Aia Tyr 75 Ser Trp Ala Phe Pro Arg Leu Gly 140 Ser Trp 155 Leu Val Asn Val Ser Gly Ser Leu 220 Leu Val 235 Ile Gly Arg Ile Gly Thr Ser 125 Met Arg Ala Ser Phe 205 His Val Asp Ile Val1 Leu Thr 110 Leu Leu Leu Arg Gly 190 Val1 Val1 Met Leu Th r Thr Phe Pro Gly Ser Thr Leu 175 Lys Val1 Gly Cys Ala 255 Arg Leu Met Val1 Lys Ala Phe 160 Pro Val Gi y Giu Gly 240 Asp <210> 177 <211> 1266 <212> DNA <213> Corynebacteriun glutamicun <22 0> <221> CDS <222> (101)..(1243) <223> RXN03142 WO 01/00804 <400> 177 gcaatttggCc aatcaacaa eataggagga ctgcgtggcg PCT/1BOO/00922 gtcaccgcaa gaacggacat aaaaeeaeac ceatcgeaac Caacggcact gttcactcec t gg Trp gtc Val1 gte Val gtg Val etc Leu get Al a tct Ser att Ile t ce Ser gat Asp 150 gtt etc Leu at g Met gga Gly ttc Phe ate Ile gc Al a tat Tyr ect Pro aca Thr 135 ga c Asp ttc gte ValI geg Ala ttt Phe gcg Ala ttt Phe tca Ser tct Ser gca Ala 120 ctg Leu ttc Phe ggc a a Asr etcj Leu geg Al a gga Gly gte ValI eta Leu ett Leu 105 agc Se r get Ala ase Dsn ctg -ttg SLeu tat Tyr gc Ala tgg Trp ggc Gly cca Pro get Ala cgt Arg a Thr tac Tyr2 ate c Thi gc' Ali a gc Ser a cg Thr ttg Leu 7?5 geg Ala tee Ser agg Arg gc t Ala aac ksn 155 :tc ccag r Gln ;atg Met -tee *Ser tee *Ser 60 *gaa Glu etg Leu ace Thr gea Ala tte Phe 140 ace c Thr I ace g~ t ac Tyr gsa Glu ttt Phe 45 ga e Asp geg Ala gtt Val get Al a gag 125 3ge :tg .e u t t tt( Let agc Sex gt t ValI egt Arg gta Vsa1 get Al a gt g Vsa1 110 gge Gly ca Pro ttc Phe ttg 1agc i Ser 15 tte Phe ate Ile ttt Phe gca Ala gtg Val 95 atg Met see Thr gca Ala tqg Trp ate Ile 175 eca Pro N~ t t( Ph( gec Ala ggC Gi y ggt Gly tea Ser 80 egt Arg ges Ala gge Gi y att Ile att I le 160 :ge krg ite al1 agtg Val1 1 tac Tyr gtt Val gca Ala ass Lys eta Leu ttt Phe ct t Leu tae Tyr geg Ala 145 see Thr sag Lys tgg Trp I ttc PhE tea Sex ecc Thr ass Lys tte Phe gt t Vsa1 gt g ValI tte Phe 130 et g Leu act rhr :eg Pro :et er ttt att ttc Phe Ile Leu ctg Leu Igag Glu gtg Val cag Gin tat Tyr ese His cag Gin 115 qgg Ala ttt Phe geg Al a gag Giu ate Ile 195 atc Ile gee Ala get Ala ate Ile ati Ile ggt Gly 100 tee Ser etc Leu gt t Vsa1 see Thr ttc Phe 180 aag Lys 9gC Gly a Thr get Ala egt Arg et g Leu eea Pro ttt Phe gtg Val gga Gl y atc Ile agt Ser 165 att Ile act Thr 115 163 211 259 307 355 403 451 499 547 595 643 691 Val Phe Gly Leu Ile Leu Thr Val Leu 170 sag sat geg gas cac gge aga gta sag Lys Asri Ala Giu His Gly Arg Val Lys 185 190 gtt gtg ese eea teg gte atg etc att gga tte tte atg etc get gte Val Val His Pro Ser Val Met Leu Ile Gly Phe Phe Met Leu Ala Val WO 01/00804 WO 0100804PCT/IBOO/00922 gga Gly gao Asp 230 gt t ValI cat His gcg Ala gct Ala caa Gin 310 att Ile atc Ile gca ctg Leu 215 act Th r gcg Ala ggt Gly ctg Leu ggc Gly 295 gcc Al a tct Ser ctg Leu got gct Al a ggc Gly atg Met gac Asp ggg GI y 280 gca Al a att Ile a og Thr ctg Leu ttg tao Tyr ctc Leu ctg Leu aac As n 265 ctt Le u ctc Leu qct Ala ctt Leu gg t Giy 345 gcc gca Ala acc Th r gtc Val 250 cog Pro atg Met acc Thr gtc Val ttc Phe 330 gga Gly gca ggc Gly gcC Ala 235 atg Met gt t Val1 got Ala ggt Gly gat Asp 315 ct g Leu ttg Leu gtg qg Val 220 gga Gly cgt Arg att Ile t tg Leu t tg Leu 300 tca Ser ttC Phe gt t ValI att atc acc ttc ctc Ile Thr Phe Leu gcg Ala ttc Phe tac Tyr gcg Ala 285 ggc Gly gt t Val1 a cc Thr gca Ala gtt Val 365 ggt Gly ttc Phe ttc Phe 270 act Thr tat Tyr ca Pro gac Asp gcg Al a 350 gtg ott Leu ct t Leu 255 ggt Gly gaa Giu 9gc Gi y agc Ser atc Ile 335 acc Thr gcg ttc Phe 240 gga Gly ttg Leu gao Asp acc Thr act Thr 320 ggc Giy gga Gly ggc aao ggc Asn Gly 225 ttt ato Phe Ile cgc att Arg Ile atc agc Ile Ser tgg cac Trp His 290 atc atg Ile Met 305 cag gtt Gin Val att ggc Ile Gly tac aac Tyr Asn gtg ctc ttc Phe gct Ala cag Gin ttc Phe 275 att Ile ccg Pro ggt Gly tta Leu gt c Val1 355 tac gcg Aila tat Tyr gao Asp 260 gcc Ala gt t Val gc Ala too Ser ggo Gly 340 a tg Met ctg caa Gin gog Ala 245 aaa Lys oto Leu ctc Leu gca Ala ggt di y 325 oca Pro tao Tyr gtt 787 835 883 931 979 1027 1075 1123 1171 1219 1266 Ala Ala Leu Ala Ala Val Ile 360 Val Ala Gly Val Leu Tyr Leu Val 370 got ttg ggt agg aaa got ago cac taagttagag cattttattg ago Ala Leu Gly Arg Lys Ala Ser His 375 380 <210> 178 <211> 381 <212> PRT <213> Corynebacteriwn giutamicum <400> i78 Val Phe Ile Leu Gly Trp Leu Val Asn Leu Thr Gin Tyr Leu Ser Phe 1 5 10 Tyr Phe Leu Ile Thr Val Met Ala Leu Tyr Ala Met Glu Ser Phe Ala WO 01/00804 PTIO/02 PCTfIBOO/00922 Val1 Al a Lys Leu Phe Leu Tyr Ala 145 Thr Lys Trp Phe Asn 225 Phe Arg Ile T rp Ile Se r Thr Lys Phe ValI Val Phe 130 Leu Thr Pro Ser Met 210 Gi y Ile Ile Ser His 290 Met Giu Val1 Gin Tyr His Gin 115 Aia Phe Al a Gi u Ile 195 Leu Phe Ala Gin Phe 275 Ile Pro Ala Ala Val Gly Phe Ala Ala Ser Ser Phe Val Ile Gly Ala Ile Ile Gly 100 Ser Leu Val1 Thr Phe 180 Lys Ala Ala Tyr Asp 260 Ala Val1 Ala Arg Leu Pro Phe Val1 Gly Ile Ser 165 Ile Thr Val Gin Al a 245 Lys Leu Leu Ala Val1 Leu 70 Ala Ser Ile Ser Asp 150 Vali Lys ValI Gi y Asp 230 Val1 His Ala Al a Gin Phe 55 Ile Ala Tyr Pro Thr 135 Asp Phe Asn ValI Leu 215 Th~r Aia Gly Leu Gly 295 Ala 40 Ala Phe Se r Ser Al a 120 Leu Phe Gly Ala His 200 Ala Gly Met Asp Giy 280 Ala Ile GI y Val1 Le u Leu 105 Ser Ala Asn Leu Glu 185 Pro Tyr Leu Leu Asn 265 Leu Leu Ala Trp Gly Pro Al a Arg Thr Tyr Ile 170 His Se r Al a Thr Val1 250 Pro Met Thr Val Thr Leu 75 Ala Ser Arg Al a As n 155 Leu Gi y Val Giy Ala 235 Met Val Ala Gi y Asp Ser Glu Leu Th r Ala Phe 140 Thr Thr Arg Met Val 220 Giy Arg Ile Le u Leu 300 Ser Asp Arg Ala Val Val Ala Ala Val 110 Giu Gly 125 Gly Pro Leu Phe Val Leu Vai Lys 190 Leu Ile 205 Ile Thr Ala Gly Phe Phe Tyr Phe 270 Ala Thr 285 Gly Tyr Val Pro Giy Se r Arg Ala Giy Ile Ile 160 Arg Val Phe Leu Phe 240 Gly Leu Asp Thr Thr 310 315 320 Gin Val Gly Ser Gly Ile Ser Thr Leu Phe Leu Phe Thr Asp Ile Gly WO 01/00804 PCT/IBOO/00922 325 330 335 Ile Gly Leu Gly Pro Ile Leu Leu Gly Gly Leu Val Ala Ala Thr Gly 340 345 350 Tyr Asn Val Met Tyr Ala Ala Leu Ala Ala Val Ile Val Val Ala Gly 355 360 365 Val Leu Tyr Leu Val Ala Leu Gly Arg Lys Ala Ser His 370 375 380 <210> 179 <211> 914 <212> DNA <213> Corynebacteriwn glutamicum <220> <221> CDS <222> <223> FRXA01150 <400> 179 cca get gee tca eta cca gcg ctg gtt gct gtg cgt itt gtt cac ggt 48 Pro Ala Ala Ser Leu Pro Ala Leu Vai Ala Val Arg Phe Val His Gly 1 5 10 ttt tet tat tci ctt gct ice ace get gtg atg gea cit gtg cag icc 96 Phe Ser Tyr Ser Leu Ala Ser Thr Al1a Val Met Ala Leu Val Gin Ser 25 gtg ati eei gca agc cgt agg gca gag ggc acc ggc tac ttc gcg ctc 144 Val Ile Pro Ala Ser Arg Arg Ala Giu Gly Thr Gly Tyr Phe Ala Leu 40 gga tcc aca ctg gct aca get tic ggc cca gca ait gcg ctg itt git 192 Gly Ser Thr Leu Ala Thr Ala Phe Gly Pro Ala Ile Ala Leu Phe Val 55 ate gat gae tic aac tac aac ace ctg tie tgg ait ace act gcg ace 240 Ile Asp Asp Phe Asn Tyr Asn Thr Leu Phe Trp Ile Thr Thr Ala Thr 70 75 agt gtt tie gge etg ate etc aec git tig ate ege aag ceg gag ttc 288 Ser Val Phe Gly Leu Ile Leu Thr Val Leu Ile Arg Lys Pro Glu Phe 90 att aag aat geg gaa eac ggc aga gta aag eca gte tgg tet ate aag 336 Ilie Lys Asn Ala Glu His Gly Arg Val Lys Pro Val Trp Ser Ile Lys 100 105 110 act gtt gig cac eca teg gte aig etc ait gga tie tic atg etc get 384 Thr Val Val His Pro Ser Val Met Leu Ile Gly Phe Phe Met Leu Ala 115 120 125 gte gga cig get tac gca ggc gtg ate ace ttc etc aac ggc tic gcg 432 Val Gly Leu Ala Tyr Ala Gly Val Ile Thr Phe Leu Asn Giy Phe Ala WO 01/00804 WO 0100804PCT/1B00100922 caa Gin 145 gcg Ala aaa Lys ct C Leu ctc Leu gca Ala 225 ggt Gly cca Pro tac Tyr gac Asp gtt Val1 cat His gcg Ala gct Ala 210 ca a Gin att Ile atc Ile gca Ala ggc Gly atg Met gac Asp 180 ggg Gly gca.
Al a att Ile acg Thr ctg Leu 260 ttg Leu acc gcc gqa gcg ggt Thr 150 gtc Val1 ccg Pro at g Met acc Thr gt C Val1 230 ttC Phe gga Gly gca Al a Ala Gly atg cgt Met Arg gtt att Val Ile gct ttg Ala Leu 200 ggt ttg Giy Leu 215 gat tca Asp Ser ctg ttc Leu Phe ttg gtt Leu Val gtg att Vai Ile 280 Ala ttc Phe tac Tyr 185 gcg Ala ggc Gly gt t Val1 acc Thr gca Ala 265 gtt Val ctt ttc Leu Phe 155 ctt gga Leu Gly ggt ttg Gly Leu gaa gaC Giu Asp ggc acc Gly Thr 220 agc act Ser Thr 235 atc ggc Ile Giy acc gga Thr Giy gcg ggc Ala Giy tt t Phe cgc Arg at c Ile tgg Trp 205 a tc le cag Gin att Ile tac Tyr gtg Val 285 Leu Tyr Leu gtt gct ttg ggt agg aaa gct agc cac taagttagag cattttattg Val Ala Leu Gly Arg Lys Ala Ser his 290 295 agc <210> 180 <211> 297 <212> PRT <213> Corynebacterium giutamicum <400> 180 Pro Ala Ala Ser Leu Pro Ala Leu Val Ala Val Arg Phe Val His Gly 1 5 10 Phe Ser Tyr Ser Leu Ala Ser Thr Ala Val Met Ala Leu Val Gin Ser 25 WO 01/00804 Val Ile Pro Ala Ser Arg Arg Ala Giu Giy Thr Gly 40 PCT/tBOO/00922 Gly Ilie Se r Ile Th r Val1 Gin 145 Aia Lys Leu Leu Aila 225 Giy Ser Asp Val Lys Vali Giy 130 Asp Val1 His Ala Ala 210 Gin Ile Thr Asp Phe Asn Vali 115 Leu Th r Ala Gi y Leu 195 Giy Al a Se r Leu Phe Gly Ala 100 His Al a Gly Met Asp 180 Cdy Al a Ile Th r *Ala Asn Leu Glu Pro Tyr.
Leu Leu 165 Asn Leu Leu Ala Leu 245 Thr Tyr 70 Ile His Se r Ala Thr 150 Val Pro Met Thr V'al 230 Phe *Ala 55 *Asn *Leu Gly Val Gly 135 Ala Met Val1 Al a Gly 215 Asp Leu Leu Phe Thr Thr Arg Met 120 ValI Gly Arg Ile Leu 200 Leu Ser Phe Val1 *Gly Leu *Val Val1 105 Leu Ile Ala Phe Tyr 185 Al a Gly ValI Thr Ala 265 Val Pro Phe Leu 90 Lys Ile Thr GI y Phe 170 Phe Th r Tyr Pro Asp 250 Al a Val1 Ala T rp, Ile Pro Gi y Phe Leu 155 Leu Gly Glu Gly Ser 235 Ile Thr Ala Ile Ile Arg Val1 Phe Leu 140 Phe Gly Leu Asp Thr 220 Thr Gly Gi y Tyr Ala Thr Lys Trp Phe 125 Asn Phe Arg Ile T rp 205 Ile Gin Ile Tyr Vali 285 Phe Ala Leu Leu Thr Pro Se r 110 Met Gly Ile Ile Se r 190 His Met ValI Gly Asn 270 Leu Phe Al a Glu Ile Leu Phe Ala Gin 175 Phe Ile Pro Gi y Leu 255 Val Tyr Pro Ilie Leu Leu Gly Gly 260 Tyr Ala Ala Leu Ala Ala Val Ile 275 280 Val Ala Leu Gly Arg Lys Ala Ser His 290 295 <210> 181 <211> 1341 <212> DNA <213> Corynebacterium glutamicum WO 01/00804 <220> <221> CDS <222> (101)..(1318) <223> RXN02964 <400> 181 ttttatatcc tagcaagggt gttgcatgat gcaataaacg PCTIBOO/00922 tggtagtttg tgttcataac aaaattgcat gatgcaataa tttcgattta aaggagaaca gtg tcc gta gct gaa Val Ser Val Ala Glu gaa Gil ctt Leu tac Tyr tee Ser tat Tyr cta Leu cca Pro gct Ala cga Arg gca Al a 150 ta c Tyr ggg Gly ttc IPhe gee Ala agc Ser att Ile gtc Val1 t tg Leu gcc Al a cg t Arg 135 gca Ala gac Asp aaa Lys c ag Gin atc Ile tca Se r att Ile act Thr c ta Leu ace Th r 120 tcc Ser ct t Leu atq M4et ctt Leu ttC Phe aag Lys att Ile gac Asp ace Thr tac Tyr 105 gcg Ala gaa Glu gga Gly ctg Leu ttt Phe ctq Leu gaa Glu gtt Val1 cgt Arg att Ile gca Ala a tc Ile ggt Giy cca Pro ~ttt Phe aca Thr gtg Val ttt Phe ate Ile ttt Phe 75 gcg Ala aac Asn atg Met act Thr gcc Ala 155 atc Ile cca Pro ttc Phe ca a Gin Gly 60 ggt Gly t gt Cys agg Arg gca Ala ggt Gly 140 cta Leu gtg Val acg Th r tac Tyr gcc Ala 45 g ca Ala cga Arg gcc Al a ttc Phe a tg Met 125 tac Tyr gca Al a gt C lal Ittt Phe ttc *Phe 30 *tct Ser gtC Val1 cgc Arg t tg Leu ctc Leu 110 gtc Val1 ctg Leu ctt Le u ttg Leu gtc Val 15 ctc Leu gaa Glu ttt Phe aag Lys t ac Tyr 95 cac His cag Gin gca Al a ttt Phe gca A.la atq Met atc Ile gt a Val1 tcc Ser att Ile 80 ctt Leu ggt Gly gag Glu ttg Leu gtc Val1 160 a cc Thr
I
gga Giy acc Thr gaa Glu agg Arg gtg Val ccc Pro gt t Val1 ct C Leu ggC Gly 145 cta Leu tcg Ser t gg Trp a cc Thr gct Ala ttt Phe ct c Leu ate Ile gga Gly att Ile 130 act Thr gga Gly gt c
V;;I
ttt Phe atg Met ggc Gly ttc Phe atc Ile gaa Glu tac Tyr 115 cca Pro acc Thr a ca Thr atc
TIP
gcc aac Ala Asn gct ttg Ala Leu ttc gca Phe Ala tcC ggc Ser Gly tca gtc Ser Val tca ttg Ser Leu 100 gct ttt Ala Phe gcg tca Ala Ser gtt tct Val Ser ttt gat Phe Asp 165 tct ttq Ser Leu 180 115 163 211 259 307 355 403 451 499 547 595 643 170 175 atc gcc gtc gtg ttc atg tac ttt aag acc agc gac cct gag cct tct wo 01/00804 WO 0100804PCTIIBOO/00922 Ile Ala Val Val Phe Met Tyr Phe Lys Thr Ser Asp Pro Glu Pro Ser 185 195 ggg Gly a tc Ile gtC Val1 230 ggt Gly cgc Arg at t Ile tt t Phe ct g Leu 310 gta Val ttt Phe t ct Ser ggt GI y gaa Glu ccc Pro 215 att Ile gct Al a agc Se r tac Tyr gcc Al a 295 gga Gly gta Val gt g Val1 gcg Ala gtg Val1 cca Pro 200 atc Ile gcc Al a ga Gly t tC Phe tt Phe 280 act Thr tac Tyr gac Asp gac Asp gca Ala 360 att Ile goc Al a ggc Gly t ac Tyr t tg Leu ctt Leu 265 gga Gly tcc Ser ggc Gly aaa Lys t La Leu 345 att Ile gcc Al a aag Lys atc Ile atc Ile ttC Phe 250 ggC Gly ttg Le u aac As n act Thr ac Thr 330 ggt Gly ggt.
Gly gga Gi y Gly ttc agc Phe Ser ttt atc Phe Ile 220 aac gca Asn Ala 235 ttc att Phe Ile aaa ctg Lys Leu ttc ttc Phe Phe tgg cac Trp His 300 ttq atg Leu Met 315 gaa ttc Glu Phe ttt ggc Phe Gly ttc gga Phe Gly atc ttc Ilie Phe 380 ttt gtt ttc Phe 205 ttg Leu ttt Phe gcC Ala cag Gin ttc Phe 285 gtt Val1 cca Pro ggt Gly ttt Phe Cct.
Pro 365 tac Tyr aaa Lys Ct t Leu gct Al a tac Tyr ga c Asp 270 gt t ValI gtg Val1 gca Ala acg Thr gga Gly 350 atg Met ctg Leu t ct Ser att Ile ga a Glu qca Al a 255 cg t Arg att Ile t tg Leu gtg Val gcc Al a 335 cct Pro tat Tyr ttc Phe att Ile t gC Cys gaa Giu 240 gt a Val cgc Arg t cc Ser tcc Ser cag Gin 320 ttc Phe att Ile gca Ala aca Thr atg Met ttt Phe 225 cgc Arg t ca Ser gga Gly tt g Leu gga Gi y 305 t cc Ser t cc Ser a tc Ile gca Ala cac His 385 a ac Asn 210 gct Ala ga t Asp atg Met ga c Asp acg Thr 290 qtC Val atc Ile act Thr ctg Leu ctg Leu 370 gct Ala cca Pro tac Tyr Ct g Leu ttt Phe aac Asn 275 att Ile att Ile gct Ala ttg Leu gga Gly 355 gca.
Ala cgC Arg aag Lys tct Se r at t Ile gtg Val 260 gtc Val ttg Leu gca Ala gtt Val ttc: Phe 340 gca Ala ggt Gi y acc Thr 739 787 835 883 931 979 1027 1075 1123 1171 1219 1267 1315 1341 375 cga gct aag aat Arg Ala Lys Asn aaa. cac cca gag cct gtc gct tta gtt Glu Pro Val Ala Leu Val Phe Val Lys His Pro 395 tagttctttc agctttccct CCC WO 01/00804 PCT/IBOO/00922 <210> 182 <211> 406 <212> PRT <213> Corynebacterium giutamicum <400> 182 Val Ser Val Ala Glu Giu Gly Lys Leu Phe Thr Pro Thr Phe Val Met 1 5 10 Gly Trp Phe Ala Asn Leu Phe Gin Phe Leu Val Phe Tyr Phe Leu Ile 25 Thr Thr Met Ala Leu Tyr Ala Ile Lys Giu Phe Gin Ala Ser Glu Val 40 Glu Ala Giy Phe Ala Ser Ser Ser Ile Val Ile Gly Ala Val Phe Ser 55 Arg Phe Phe Ser Gly Tyr Ile Ile Asp Arg Phe Gly Arg Arg Lys Ile 70 75 Val Leu Ilie Ser Val Leu Val Thr Thr Ile Ala Cys Ala Leu Tyr Leu 90 Pro Ile Glu Ser Leu Pro Leu Leu Tyr Ala Asn Arg Phe Leu His Gly 100 105 110 Val Gly Tyr Ala Phe Ala Ala Thr Ala Ile Met Ala Met Val Gin Glu 115 120 125 Leu Ile Pro Ala Ser Arg Arg Ser Glu Gly Thr Giy Tyr Leu Ala Leu 130 135 140.
Giy Thr Thr Val Ser Ala Ala Leu Gly Pro Ala Leu Ala Leu Phe Vai 145 150 155 160 Leu Gly Thr Phe Asp Tyr Asp Met Leu Phe Ile Val Val Leu Ala Thr 165 170 175 Ser Val Ile Ser Leu Ile Ala Val Val Phe Met Tyr Phe Lys Thr Ser 180 185 190 Asp Pro Glu Pro Ser Gly Glu Pro Ala Lys Phe Ser Phe Lys Ser Ile 195 200 205 Met Asn Pro Lys Ilie Ile Pro Ile Giy Ile Phe Ile Leu Leu Ile Cys 210 215 220 Phe Ala Tyr Ser Gly Val Ile Ala Tyr Ile Asn Ala Phe Ala Giu Giu 225 230 235 240 Arg Asp Leu Ile Thr Gly Ala Giy Leu Phe Phe Ile Ala Tyr Ala Val 245 250 255 WO 01/00804 Met Phe Val Met 260 Asp Asn Val Val 275 Thr Ilie Leu Ser 290 Val Ile Ala Gly Ile Ala Val Gly 325 Thr Leu Phe Leu 340 Leu Gly Ala Val 355 Leu Ala Gly Val 370 Ala Arg Thr Asp Val Ala Leu Val 405 PCTIBOO/00922 Ser Tyr Ala 295 Gly Val1 Val Ala Val1 375 Ala Leu 265 Gly Ser Gly Lys Leu 345 I le Ala Asn Gly Lys Leu Phe Asn Trp Thr Leu 315 Thr Glu 330 Gly Phe Gly Phe Gly Ile Gly Phe 395 Ar g Se r Se r Gin 320 Phe Ile Al a Thr Glu 400 <210> 183 <211> 1006 <212> DNA <213> Corynebacterium glutamicum <22 0> <221> CDS <222> (101)..(1006) <223> FRXA02i16 <400> 183 ttttatatcc tagcaagggt gttgcatgat gcaataaacg aaaattgcat gatgcaataa tttcgattta aaggagaaca gaa ggg aaa ctt ttt aca cca acg ttt gtc atg Glu Gly Lys Leu Phe Thr Pro Thr Phe Val Met 15 ctt ttc cag ttc ctg gtg ttc tac ttc ctc atc Leu Phe Gin Phe Leu Val Phe Tyr Phe Leu Ile 30 tac gcc atc aag gaa ttt caa gcc tct gaa gta tggtagtttg tgttcataac gtg tcc gta gct gaa Val Ser Val Ala Glu 1 gga tgg ttt gcc aac Gly Trp Phe Ala Asn acc acc atg gct ttg Thr Thr Met Ala Leu gaa gct ggc ttc gca WO 01/00804 PCT/IBOO/00922 Tyr Ala Ile Lys Glu Phe Gin Ala Ser Glu Val Giu Ala Gly Phe Ala 45 t cc Ser tat T yr ct a Leu cca Pro gct Ala cga Arg gca Ala 150 t ac Tyr atc Ile ggg Gly atc Ile gte Val1 230 ggt Gly age Ser att Ile gt c Val1 ttg Leu gce Ala cgt Arg 135 gea Al a gac Asp gcc Al a ga a Gi u ccc Pro 215 att Ilie gct Al a tca *Ser att Ilie act Thr cta Leu ace Thr 120 t cc Ser ctt Leu atg Met gt c ValI c ca Pro atc Ile gcc Ala gga Gly ati Il gac As; aec Thr tac Tyr 1 05 gcg Ala gaa Glu gga Gly ctg Leu gtg Val 185 gee Al a ggc Gl y tac Tyr L tg Leu -gtt SVal -cgt )Arg -att Sle -gca *Ala atc Ile ggt *Gly cca Pro ttt Phe 170 ttc Phe aag Lys ate Ile atc Ile ttC Phe 250 at c Ile tt t Phe 75 geg Ala aac Asn atg Met act Thr gcc Al a 155 ate Ile atg Met ttC Phe ttt Phe aac As n 235 ~t Phe *Gly ggt *Gly tgt Cys agg Arg gca Ala ggt GI y 140 cta Leu gtg ValI tac Tyr age Ser atc Ile 220 gca Ala att Ile gca Ala cga Arg gcc Ala ttc Phe at g Met 125 tac Tyr gca Al a gtc ValI ttt Phe tte Phe 205 ttg Leu ttt ?he ;cc l a gtC Val cgc Arg ttg Leu ctc Leu 110 gte Val1 ctg Leu ctt Leu t tg Leu a ag Lys 190 aaa Lys ct t Leu get Ala tac Tyr ttt Phe aag Lys tac Tyr 95 cac His cag Gin gca Ala ttt Phe gca Al a 175 ace Thr t Ct Ser a tt Ile gaa Glu gca Al a tcc Ser att Ile 80 ct t Leu ggt Gly gag Glu ttg Leu gte ValI 160 acc Thr age Ser att Ile tgc Cys gaa Glu 240 gtaI Val agg Arc gtg ValI ccc Pro gt t ValI etc Leu ggc Gi y 145 eta Leu t eg Ser gac Asp atg Met ttt Phe 225 :qe A.rg tea Ser ttt Phe ete *Leu ate Ile gga Gly att Sle 130 act Thr gga Gly gte Val1 cct Pro aae Asn 210 get Ala gat Asp atg Met ttc Phe ate Ile ga Glu tac Tyr 115 ccea Pro ace Thr aca Thr ate Ile gag Glu 195 cca Pro tac Tyr ctg Leu tt t Phe tee Ser tea Ser tea Ser 100 get Ala geg Ala gt t Val ttt Phe t ct Ser 180 ect Pro a ag Lys tet Ser att Ile gtg Val1 260 9ge Gly gte Val ttg Leu ttt Phe tea Se r tct Se r gat Asp 165 ttg Leu tct Ser ate Ile 9ge Gly aeg Thr 245 atg Met 307 355 403 451 499 547 595 643 691 739 787 835 883 ege age tte ctt ggc aaa etg eag gac cgt ege gga gac sac: gtc gtt Arg Ser Phe Leu Gly Lys Leu Gin Asp Arg Arg Gly Asp Asn Val Val WO 01/00804 265 270 att tac ttt gga ttg ttc ttc ttc gtt Ilie Tyr Phe Gly Leu Phe Phe Phe Val 280 2B5 ttt gcc act tcc aac tgg cac gtt gtg Phe Ala Thr Ser Asn Trp His Val Val 295 300 <210> 184 <211> 302 <212> PRT <213> Corynebacterium giutamicum <400> 184 Val Ser Val Ala Glu Glu Gly Lys Leu PCT/IBOO/00922 275 att tcc ttg acg ait ttg tcc Ile Ser Leu Thr Ile Leu Ser 290 1006 1 Gly Trp Thr Thr Giu Ala Arg Phe Val Leu Pro Ile Val Gly Leu Ile 130 Gly Thr 145 Leu Gly Ser. Val Asp Pro Met Asn Ala Al a Phe Ser Ser Ser 100 Ala Al a Val1 Phe Ser 180 Pro Lys 5 Asn Leu Ala Gly Val Leu Phe Ser Ser Asp 165 Leu Ser Ile Leu Phe Tyr Ala Ser Ser 55 Tyr Ile 70 Leu Vai Pro Leu Ala Ala Arg Arg 135 Ala Ala 150 Tyr Asp Ile Ala Gly Glu Ile Pro Phe Lys Ile Asp Thr Tyr 105 Al a Gi u Gly Leu Val1 185 Ala GI y Phe Thr 10 Leu Vai Giu Phe Val Ile Arg Phe le Ala 90 Ala Asn Ile Met Gly Thr Pro Ala 155 Phe Ilie 170 Phe Met Lys Phe Ile Phe Pro Phe Gin Gly Gly Cys Arg Ala Gi y 140 Leu Val Tyr Ser Ile Th r Tyr Ala Ala Arq Ala Phe Met 125 Tyr Al a Val1 Phe Phe 205 Leu Val1 Leu Giu Phe Lys Tyr His Gin Al a Phe Ala 175 Thr Ser Ile WO 01/00804 210 215 Phe Ala Tyr Ser Gly Val Ile Ala Tyr Ile Asn 225 230 235 Arg Asp Leu Ile Thr Gly Ala Gly Leu Phe Phe 245 250 Ser Met Phe Val Met Arg Ser Phe Leu Gly Lys 260 265 Gly Asp Asn Val Val Ilie Tyr Phe Gly Leu Phe 275 280 Leu Thr Ile Leu Ser Phe Ala Thr Ser Asn Trp 290 295 <210> 185 <211> 568 <212> DNA <213> Corynebacterium glutamicun <22 0> <221> CDS <222> (568) <223> RXA00858 <400> 185 ttttgttttt cagatgcatg ttagatqcgt tgagggaeaa tcttaaattg tctaaecaag aaccggaggt tetttttgt.
PCT/IBOO/00922 220 Ala Phe Ala Glu Glu 240 Ile Ala Tyr Ala Val 255 Leu Gin Asp Arg Arg 270 Phe Phe Val Ile Ser 285 His Val Val 300 gcc Ala ga t Asp tee Ser gtg ValI Gly ga t Asp ate Ile cgc Arg ttc Phe t gg T rp ggt Gly geg Ala gca Al a ace Thr tac Tyr ggc Gly tac Tyr ct g Leu gtg ValI c ca Pro gta Val gag Glu gt g Val1 atc Ile get Ala gag Glu ctc Leu ggt Gly gag Glu 80 ggt Gly gggtggggga gaeetecggt atg gaa gta aae tta Met Glu Val Asn Leu 1 gqc ttc tte att tte Gly Phe Phe Ile Phe ccc act ate aaa gaa Pro Thr Ile Lys Glu gcc tgt gtt ttc ggc Ala Cys Val Phe Gly aac cca cac cag eac Asn Pro His Gin His aag gcg ttg agt gtt Lys Ala Leu Ser Val tet tte aag att Cct Ser Phe Lys Ile Pro WO 01/00804 WO 0100804PCTIIBOO/00922 cge aag tac cag cag aag gtt ctg Arg Lys Tyr Gin Gin Lys Val Leu 105 gte ttc cgc ctg gca ttc ate cte Val Phe Arg Leu Ala Phe Ilie Leu 120 125 tgg tcc gat gte ttc tac atc tte Trp Ser Asp Val Phe Tyr Ile Phe 135 140 gtg aag gct cct. gtg cac gag Val Lys Ala Pro Val His Giu 150 155 <210> 186 <211> 156 <212> PRT <213> Corynebacterium giutamicum 95 100 ctc ate ggt atc gcg ctg gca ctg Leu Ilie Giy Ile Ala Leu Ala Leu 110 115 gca ggt get gca gtt atc gaa gcc Ala Gly Ala Ala Val Ile Glu Ala 130 tee atc tgg ctg ate tac ace get Ser Ile Trp Leu Ile Tyr Thr Ala 145 <400> 186 Met Glu Val Asn Leu Ala Thr Trp Leu Ile Thr Ile Ala Val Ile Ala 1 Gly Phe P Pro Thr I Ala Cys V Asn Pro H Lys Ala L Ser Phe L Ilie Ala L, 1 Ala Val I.
130 Leu Ile T, 145 <210> 187 Ilie Lys Phe Gin Ser Ile 100 Al a Giu Thr Phe Asp Giu Ser Gly Val His Gly 70 Val Asp Pro Arg Leu Val Ala Trp Ala Val 150 Phe Al a Phe 55 Ile Asn Lys Phe Ser 135 Lys Ser Trp Trp Phe Phe Gin 105 Leu Val1 Pro Val1 Leu Ala Thr Phe Lys Phe Tyr His 155 Arg Phe Trp Gly Ala Val1 Ile Ile 140 Giu WO 01/00804 <211> 975 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> (952) <223> RXA02305 <400> 187 tatgcgcgca ggtgtctact ggtgacgcag ccgacgacga caaacgatga cttcgatccc gaaaagtgga ggaacatgta PCT/IBOO/00922 ttattttgac gaagccaccg atg cca gcc ttt gag Met Pro Ala Phe Glu gca Ala gca Ala gaa Giu gca Ala at t Ile gca Ala gga Gly att Ile aca Thr atc atg Met aaa Lys gtc Val1 ggg GI y acc Thr gaa Glu cgc Arg gag Glu tcC Se r 135 gat c ca Pro ict Se r aa c As n ct g Leu tac Tyr cig Leu at g Met cca Pro 120 gtg Val tic gga Gi y gca Ala gat Asp atc Ile ttc Phe ggt Gly atc Ile 105 qgc Gly tgg T rp tac atc Met cac His ggc Gly gat Asp ct C Leu gga Gly cta Leu aqc Se r cat His ggt ccg *Pro ttc Phe tac *Tyr cag Gin tc Ser 75 cga Arg gct Ala gag Glu gaa Giu gag tat Tyr tac Tyr cgc Arg cgc Arg 60 tac Tyr att Ile gt t ValI gaa Glu tc Leu 140 t g tgg Trp gaa *Giu *atg *Met 45 ggt Gly gati Asp ctg Leu gat Asp t ca Ser 125 acc Thr ttc Phe atc Ile aac Asn 30 gct Ala ga a Glu ct g Leu gcc Al a act Thr 110 ttC Phe act rhr act 1'hr gac Asp 15 gt t Val cqi Arg tca Ser gat Asp gag Glu 95 gcc Al a gt c Val1 gt c Val1 t gg Trp ctg Leu ctc Leu ct g Leu a gc Ser gcc Ala 80 cca Pro ggc Gly gct Ala tcc Ser aca Th r 160 1 tcc Ser qgc Gly cag Gin atc Ile act Thr act Thr gca Ala gct Al a aaa Lys 145 acc Thr a cc Thr igg Trp gga Gly ccg Pro gca Ala gac Asp ctg Leu ggt Gly 130 tat Tyr tct Ser tcg Ser ga a Gi u ct a Leu ga t Asp aag Lys gig Val1 ttc Phe 115 gaa Gi u icc Se r gaa Glu ga c Asp 20 att Ile ccc Pro acc Thr aag Lys cac His 100 ggc Gi y cca Pro gaa Giu atg Met att Ile gaa Glu gig Val t gg Trp aic Ile ttg Leu gt i Val1 ggc Gly gct Ala gct Ala 165 115 163 211 259 307 355 403 451 499 547 595 Ile Asp Phe Tyr Gly Glu Leu agt gct gaa gac gat agi tic cgc tac acc acc gca tig gct gac ggi Ser t cc Ser gtt Val gct Al a tgg Trp 230 gcc Al a gaa Glu ttc Phe WO 01/00804 Ala Glu Asp Asp 170 gcc ttt gct gga Ala Phe Ala Gly 185 cca agc ttc tgg Pro Ser Phe Trp 200 gca gcg aag gcc Ala Ala Lys Ala 215 gac tca gaa ttt Asp Ser Glu Phe aca att acc ttg Thr Ile Thr Leu 250 ggc gat gat ctc Gly Asp Asp Leu 265 cgc aag caa gaa Arg Lys Gin Glu 280 PCT/IBOO/00922 Se r att I le cag Gin a ag Lys ggC Gly 235 tgt Cys t tc Phe gga Gly Arg Tyr Thr Thr Ala Leu Ala 175 gat gcc aaa ggc cac ttc cca Asp Ala Lys Gly His Phe Pro 190 195 tac ctt ggc gtg ctc aac gcc Tyr Leu Gly Val Leu Asn Ala 205 210 ttt ggt ggc gat gtt att cgt Phe Gly Gly Asp Val Ile Arg 225 atg gtt ctc atc tct gat tcc Met Val Leu Ile Ser Asp Ser 240 gta gag gaa tac gtc gag gaa Val Glu Glu Tyr Val Glu Glu 255 atc gat ctc agt gct ttc gaa Ile Asp Leu Ser Ala Phe Glu 270 275 taatcctaca gcgccatgga gga Asp 180 cct.
Pro gat Asp aag Lys act Thr gca Ala 260 gag Glu <210> 188 <211> 284 <212> PRT <213> Coryriebacterium glutamicum <400> 188 Met Pro Ala Phe Glu Ala Met Pro Gly 1 5 Ser Thr Ser Asp Ile Ala Lys Ser Ala 25 Gly Trp Glu Ilie Giu Glu Val Asn Asp 40 Gin Gly Leu Pro Val Ala Gly Leu Ile Ilie Pro Asp Thr Trp Ilie Thr Tyr Phe 70 Thr Ala Lys Lys Ile Ala Glu Leu Gly Thr Asp Val His Leu Gly Arg Met Ile Met 10 His Gly Asp Leu Gly 90 Leu Trp Glu Met Gly Asp Leu Asp Ile Asp Asn Val Ala Arg Glu Ser Leu Asp Ala Glu Thr Ala Leu Leu Le u Ser Al a s0 Pro Gly Ala Al a Lys 145 Thr Ala His Leu Val 225 Ser Val1 WO 01/00804 100 Leu Phe Gly Val 115 Gly Glu Pro Gly 130 Tyr Ser Glu Ala Ser Glu Met Ala 165 Leu Ala Asp Gly 180 Phe Pro Pro Gin 195 Asn Ala Asp Asp 210 Ile Arg Lys Pro Asp Ser Thr Gly 245 Giu Giu Ala Ala 260 Glu Ser 135 Asp Ala Ala Pro Ala 215 Asp Th r Gly 105 Pro Gly Ser 120 Val Trp His Phe Tyr Gly Glu Asp Asp 170 Phe Ala Gly 185 Ser Phe Trp 200 Ala Lys Ala Ser Glu Phe Ile Thr Leu 250 Asp Asp Leu 265 Giu Glu Giu Leu 140 Glu Leu 155 Ser Phe Ile Phe Gln Ser Lys Glu 220 Gly .Axg 235 Cys Glu Phe Asp 110 Phe Thr Thr Tyr Al a 190 Leu Gly Val1 Glu Asp 270 PCT/IBOO/00922 Ala Phe Glu 275 Glu Gln Phe Arg Gln Glu Gly Gin <210> 189 <211> 948 <212> DNA <213> Corynebacterium glutainicum <22 0> <221> CDS <222> (925) <223> RXA00084 <400> 189 tcacccttgt cgataccagc tactgggtat ctggcgtcgg tccacttggc ggcagcaaag tcttggaaga catcgatgcc ttcctcgacg cacagcaata atg tee aca get etc 115 Met Ser Thr Ala Leu 1 ccc gat cag etc aag tgg gaa tac agt gcc tte ccc gtg cag ate tcg 163 Pro Asp Gln Leu Lys Trp Glu Tyr Ser Ala Phe Pro Val Gin Ile Ser 15 WO 01/00804 WO 0100804PCTIIBOO/00922 cag aag caa egg ctt agt ccc Gin Lys Gin Arg Leu Ser Pro ggc tte atg Gly Phe Met 30 cgg atc ace gtc act ggt Arg Ile Thr Val Thr Gly gac Asp ct g Leu ga c Asp ttt Phe gt C Val1 cct Pro ga a Gi u gga Gi y 150 ggC Gly aaa Lys gta Val1 gct Ala cct Pro aag Lys atc Ile gaa.
Giu cca Pro cga Arg teg Ser cta Leu 1235 atc Ile gat Asp gta Val1 ttg Leu tac Tyr 215 tca Ser ctc Leu att Ile ccc Pro gcg Ala ccc Pro gga Gly 120 atc Ile ace Thr tgt Cys cct Pro ate Ile 200 a aa Lys It a /ai.
cga Arg cca Pro act Th r ga c Asp ga a Giu 105 cca Pro ate Ile tat Tyr gca Ala act Thr 185 c Ala gca Ala cacI His t t( Phe agc Se i ccc Prc caa Gin cta Leu qt a Val acc Thr cat His tca Ser 170 a eq Thr ga t A~sp aag Lys :tc Phe tt Phe ccg Pro cca Pro 75 ega Arg tgc Cys tec Ser 9qc Gly ccg Pro 155 gct Ala gt t Val agc Ser gtc Val tgg Trp 235 ggc Gi y gct Aia 60 ceg Pro ccg Pro gaa Giu aga Arg ect Pro 140 act Thr ccc Pro tt C Phe tcc Ser ttc Phe 220 3tC Ile cag Gin 45 ggg Gi y aca Thr ate Ile gta Val t gg T rp 125 gac Asp tct Ser gcg Ala ctc Leu ace Thr 205 caa Gin gcc Ala ptgg Trp aac Asn a cg Thr ttg Leu gac Asp 110 gca.
Ala gt a Val1 gcg Ala ate Ile cac His 190 aag Lys tgg Trp ggt Gly( gg t Gly ate Ile t gg Trp cgc Arg 95 at t Ile aag Lys ege Arg ate Ile gca Ala 175 gt a Val1 et c Leu gct jaa 3lu ttg Leu cca 1Pro ctt Leu 80 acc Thr gat Asp aac Asn gca Ala gat Asp 160 aat Asn ga C Asp act Thr tca Ser act Thr gac Asp ga t Asp cct Pro tac Tyr ate Ile t gc Cys gga Giy 145 cgc Arg ate Ile agc Ser ttc Phe gcc Al1a 225 age Ser caa Gin tte Phe egt Arg ace Thr tat Tyr agt Ser 130 ga a Gi u ct c Leu gtc Val eta Leu gaa Giu 210 aat Asn atg Met cgc Arg gga Giy get Ala cca Pro ct t Leu 115 gtt Val1 ace Thr t gt Cys aat Asn gaa Giu 195 gac Asp gca Ala gtg Val1 ate Ile at t Ile aag Lys tct Ser 100 cac His gac Asp ggc Gly etc Leu caa Gin 180 gat Asp ate Ile gca Ala cge Arg aaa Lys etc Leu tet Ser gcg Ala aac Asn gat Asp t ac Tyr ate Ile 165 tea Se r ga t Asp gac Asp gat Asp tte Phe 245 211 259 307 355 403 451 499 547 595 643 691 739 787 835 230 att cgc aaa gaa eta ate aac age tac cga gtt gat tee tea cga ate WO 01/00804 PCTIIBOO/00922 Ile Azg Lys Giu Leu Ile Asn Ser Tyr Arg Val Asp Ser Ser Ar Ile 250 255 260 act ttc ctc ggc tac tgg aaa tac ggc cga cga acc gta gac 925 Thr Phe Leu Gly Tyr Trp Lys Tyr Gly Arg Arg Thr Val Asp 265 270 275 tagctttcag attcagaccc: cag 948 <210> 190 <211> 275 <212> PRT <213> Corynebacterium giutamicun <400> 190 Met Ser Thr Ala Leu Pro Asp Gin Leu Lys Trp Giu Tyr Ser Ala Phe 1 Pro Ile Asp Asp Pro Tyr Ile Cys Gly 145 Arg Ile Val1 Thr Gin Phe Arg Thr Tyr Se r 130 Gi u Leu ValI Gin Val1 Arg Gly Ala Pro Leu 115 Vai Thr Cys Asn Ile Thr Ile Ile Lys Se r 100 His Asp Gly Leu Gln 180 5 Ser Gin Lys Gly Asp Lys Lys Leu Ile 55 Leu Asp Giu 70 Ser Phe Pro Ala Val Arg Asn Pro Ser Asp Glu Leu 135 Tyr Giy Ile 150 Ile Gly Asp 165 Ser Lys Val Asp Val Leu Gin Arg 25 Leu Arg 40 Ile Pro Pro Thr Ala Asp Pro Giu 105 Giy Pro 120 Ile Ile Thr Tyr Cys Aia Pro Thr 185 Ile Ala 200 Leu Phe Ser Pro Gin 90 Leu Val1 Thr His Ser 170 Thr Asp Ser Phe Pro Pro 75 Arg Cys Ser Gly Pro 155 Al a Val1 Ser Pro Gi y Al a Pro Pro Glu Arg Pro 140 Thr Pro Phe Ser Gly Gin Gly Thr Ile Val1 Trp 125 Asp Ser Aila Leu Thr 205 Phe Trp Asn Th r Leu Asp 110 Ala Val1 Aila Ile His 190 Lys Met Gly Ile Trp Arg Ile Lys Arg Ile Ala 175 Val1 Leu Arg Leu Pro Leu Thr Asp As n Al a Asp 160 Asn Asp Thr Ser Leu Giu Asp 195 Phe Giu Asp Ile Asp Aia 210 Lys Aia *Lys Vai Gin Trp Ala Ser WO 01/00804 PCT/IBOO/00922 Ala Asn Ala Ala Asp Pro Ser Val His Phe Trp Ile Ala Gly Glu Thr 225 230 235 240 Ser Met Val Arg Phe Ilie Arg Lys Glu Leu Ile Asn Ser Tyr Arg Val 245 250 255 Asp Ser Ser Arg Ile Thr Phe Leu Gly Tyr Trp Lys Tyr Gly Arg Arg 260 265 270 Thr Val Asp 275 <210> 191 <211> 468 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> (445) <223> RXA00843 <400> 191 gccctgatgc gaaaccggcg ccaacaatga tgccgacgaa tttgaataat catggaacaa accttagtag gctcaacgtt tte Phe cgc Arg ccc Pro gtc Val1 ctg Leu cat His cgc Arg aat ccg Asn Pro aag gac Lys Asp get tcc Ala Ser gac ggc Asp Gly cca gaa Pro Glu agg ctc Arg, Leu gcg cgc Ala Arg cgt tgt Arg Cys att gag Ile Glu gag ctc Glu Leu atc aga Ile Arg aca cct Thr Pro 75 ctt cag Leu Gin ccc aaa Pro Lys tcc Ser cct Pro aaa Lys ace Thr gaa Glu cgt Arg ate Ile aca Thr gaa Gi u ga a Giu 45 cgc Arg act Thr ccg Pro gac Asp tee Se r att Ile 30 eta Leu gaa Glu gag Glu atc Ile gtc Val aga aat Arg Asn 15 gtt cag Val Gin ttc aat Phe Asn get gag Ala Glu ett ate Leu Ile 80 gtg gtg Val Val 95 att gae Ile Asp ggcaaatgec actettagga atg aaa gte acg att Met Lys Vai Thr le 1 aec ctc get tac ctc Thr Leu Ala Tyr Leu tat ctc aaa gac acg Tyr Leu Lys Asp Thr acg ctg gga att cca Thr Leu Giy Ile Pro tac aca gaa ctg ggc Tyr Thr Giu Leu Gly gac gcc ate gtt gcc Asp Ala Ile Val Ala aeg gcc aaa gge gcg Thr Ala Lys Gly Ala 100 agc atc ttg Ser Ile Leu 115 163 211 259 307 355 403 445 WO 01/00804 105 110 tgacaacatt ttgtaqagca acc <210> 192 <211> 115 <212> PRT <213> Corynebacterium glutamicum <400> 192 Met Lys Val Thr Ile Phe His Asn Pro 1 5 Thr Leu Ala Tyr Leu Arg Asp Lys Asp Tyr Leu Lys Asp Thr Pro Thr Ala Ser Thr Leu Gly Ile Pro Val His Asp Gly Tyr Thr Glu Leu Gly Leu Ser Pro Glu 70 Asp Ala Ilie Val Ala His Pro Arg Leu Thr Ala Lys Gly Ala Ar Ile Ala Arg 100 105 Ser Ile Leu 115 PCTIBOOIOO922 Arg Asn Val Gin Phe Asn Ala Glu Leu Ile Val Val1 Ile Asp <210> 193 <211> 432 <212> DNA <213> Corynebacterium qiutamicum <22 0> <221> CDS <222> (409) <223> RXA01052 <400> 193 tatggccaac cctaggggga tggcctgtgt gttcactgtt aggtttcctc aaaatcttta acgaacaacg aagagcttgc ccgagagtat cttgggtcgc atg gac aca aaa. tta 115 Met Asp Thr Lys Leu 1 ggc gct gaa ttg ggt act gaa ttt gat ctc att gtt gtt ggt ttc ggc 163 Gly Ala Glu Leu Gly Thr Giu Phe Asp Leu Ile Val Val Gly Phe Gly 15 WO 01/00804 aaa gca ggc aag act atc gcg atg aaa cgc Lys Ala Gly Lys Thr Ile Ala Met Lys Arg gtc gca ctg atc gag cag agt cca cag atg Val Ala Leu Ilie Giu Gin Ser Pro Gin Met aat gta ggt tgc atc ccc acg aag, aag ttg Asn Val Gly Cys Ile Pro Thr Lys Lys Leu ggc aag gat ttc ccg gat gcg gtt gtg gcg Gly Lys Asp Phe Pro Asp. Ala Val Val Ala aag ctg aat gcc aag aat ctt gcg atg gcc Lys Leu Asn Ala Lys Asn Leu Ala Met Ala cgt cat tgatggaaaa gctacgttta cag Arg His <210> 194 <211> 103 <212> PRT <213> Corynebacterium glutamicum <400> 194 Met Asp Thr Lys Leu Gly Ala Glu Leu Gly 1 5 10 Val Val Gly Phe Gly Lys Ala Gly Lys Thr Ala Ala Gly Asp Lys Val Ala Leu Ile Giu Gly Gly Thr Cys Ile Asn Val Gly Cys Ilie Phe Glu Thr Ala Thr Gly Lys Asp Phe Pro Asp Gin Leu Ile Gly Lys Leu Asn Ala Lys 90 Asp Lys Gly Val Thr Arg His 100 <210> 195 <211> 543 <212> DNA <213> Corynebacteriun glutamicum PCT/IBOO/00922 211 259 307.
355 403 Leu Arg Met Leu Ala Al a WO 01/00804 WO 0100804PCT/IBOO/00922 <220> <221> CDS <222> (520) <223> RXA01053 <400> 195 ttgcgatggc cacagacaag ggtgtcaccc gtcattgatg gaaaagctac qtttaeagct agccacgaaa tcacaagtaa cttcaggtag tgacactctt gtg ctg tat gcg cca Val Leu Tyr Ala Pro aeg Thr ggC Gly t eg Ser ttg Leu at c Ile gag Glu aac Asn gac Asp att gtg Ile Val acc gac Thr Asp ccc etg Pro Leu gaa ttt Glu Phe gac cgt Asp Arg ctg gcc Leo Ala gct gaa Ala Glu cac gac His Asp 120 ate aac Ile Asn aat ccg Asn Pro ccg aag Pro Lys gee acg Ala Thr ggt gaa Gly Glu aaa ac Lys Thr etc ace Leu Thr 105 ctc ctc Leu Leu a eg Thr cat His ca c His ct t Leu ttg Leu 75 gac Asp gga Gly gee Ala ggc tcc Gly Ser gtt ttt Val Phe cte geg Leu Ala 45 tie agt Phe Ser ccg ctg Pro Leu ctg gag Leo Glu ttc age Phe Ser gac gee Asp Ala 125 acg Thr gat Asp atc Ile qga Gly aaa Lys gee Al a ggt Gly 110 gca gte Val1 act Thr ggc Gly ggC Gly ttc Phe gga Gly etc Leu ttt ccc Pro at t Ile Gly aaa Lys agg Arg ace Thr ate Ile t eg gte Val1 ca c His ate Ile a cc Thr gta Val ctc Leu 100 ctc Leu gac Asp Ala Leo Phe Ala Ser Ala 130 cac cga egg egg cct tgaacaggcg ggcatcaaaa cag Arg His Arg Arg Ala Arg Pro 135 140 <210> 196 <211> 140 <212> PRT <213> Corynebacterium glutamicum <400> 196 Val Leo Tyr Ala Pro Thr Ile Val Ile Asn Thr Giy Ser Thr Pro Val WO 01/00804 WO 0100804PCTIBOO/00922 1 5 Ile Pro Asn Val Pro Gly Thr Asp Asn Pro His Gly Ile Gin His Ile Ser Pro Leu Pro Lys His 40 Gly Gly Pro Ilie Gly Leu Glu Phe Ala Thr Leu 55 Ser Lys Val Thr Ile Ile Asp Arg Gly Glu Leu 70 Asp Arg Glu Val Ala Glu Leu Ala Lys Thr Asp Ile Thr Phe Leu Asn Asn Ala Giu Leu Thr Gly 100 105 Thr Ilie Ala Leu Lys Asp His Asp Leu Leu Ala 115 120 Ala Ser Ala Asp Ala Arg His Arg Arg Ala Arg 130 135 <210> 197 <211> 612 <212> DNA <213> Corynebacterium giutamicum <220> <221> CDS <222> (101)..(589) <223> RXA01054 <400> 197 gacctcctcg ccgacgecgc actttttgca tcggccgacg ccttgaacag gcgggcatca aaacaggcac gcgtggggag Val Leu Phe Pro Leu Phe Asp Pro 140 Phe Al a Ser Leu Giu Ser Ala 125 cccggcaccg acgggctcgg gtg cti gtc gac gee cac His ggc GI y ct g Leu atc etc egg Leu Arg ggc ceg Gly Pro gat caa Asp Gin ccc ace atc Ile ace Thr gga Gly ttc gac ggc Asp Gly tac gtg Tyr Val aca ggt Thr Giy 45 atc gaa atc ttc Ile Phe tcc tac Ser Tyr aag aaa Lys Lys ccg ecg Val Leu Val Asp Ala 1 get gta ggt gat gtc aat Ala Val Gly Asp Val Asn gat gac cac cgc att gtg Asp Asp His Arg Ile Vai tec att gca cac cga ctg Ser Ile Ala His Arg Leu tta tcc ace ate ggt gac 115 163 211 259 307 WO 01/00804 Ile Pro Thr Thr Thr Phe Ile Giu Pro Pro aac act gaa ggg gaa aat gtg gtg gtg aaa Asn Thr Giu Gly Giu Asn Val Val Val Lys 75 atg ccg atc gtt ccc cga cca gag att att.
Met Pro Ile Val Pro Arg Pro Giu Ile Ile gtg aag ttt ttc gtc gac aag caa tct gat Vai Lys Phe Phe Val Asp Lys Gin Ser Asp 105 110 ttg tac tgc gcc gac tcc cag gag ctc atc Leu Tyr Cys Ala Asp Ser Gin Giu Leu Ilie 120 125 atg cgg cat ggc gtc acc gcc tcc gag ctt Met Arg His Giy Vai Thr Ala Ser Giu Leu 135 140 cac ccc gcc acc tcg gag atc ttc aac caa His Pro Ala Thr Ser Giu Ile Phe Asn Gin 150 155 taacqcagcg gatcgaacgg ctt <210> 198 <211> 163 <212> PRT <213> Corynebacterium glutamicun <400> 198 Val Leu Val Asp Ala His Leu Arq Thr Asn 1 5 Vai Gly Asp Val Asn Giy Giy Pro Gin Phe Asp His Arg Ile Vai Leu Asp Gin Leu Ala Ilie Ala His Arg Leu Ile Pro Thr Thr Thr Ser Thr Ile Gly Asp Asn Thr Giu Gly Giu 70 Ala Leu Ilie Ala Asp Met Pro Ile Val Pro Gin Pro His Gly Met Val Lys Phe Phe Val 100 105 PCT/IBOO/00922 Leu aaq Lys aac Asn gcg Al a aac Asn ggc Gi y tta Leu 160 Ile Thr Gi y Phe Asn Arg Asp WO 01/00804 Leu Leu Gly Ala Thr Leu Tyr Cys Ala Asp Ser Gin Glu Leu Ile Asn 115 120 125 Thr Val Ala Leu Ala Met Arg His Giy Val Thr Ala Ser Glu Leu Gly 130 135 140 Asp Gly Ilie Tyr Thr His Pro Ala Thr Ser Giu Ilie Phe Asn Gin Leu 145 150 155 160 Leu Giy Ser PCT/IBOO/00922 <210> 199 <211> 561 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> (101)..(538) <223> RXN03123 <400> 199 agctctacca acgcgcctac accttgacca acgtggatgc cgatgccggt acctttgacc tggcttttgt gctgcacgag ccgctggggc ccgcctcggc gtg ggc gac gcg ctg Val Gly Asp Ala Leu cga Arg gcc Ala acc Thr at c Ile ttc Phe gaa Glu ggC Gly atc Ile tct Ser cet Pro gat Asp caa Gin gga aag Giy Lys gat cca Asp Pro cca gcg Pro Ala acc gcg Thr Ala ccc cag Pro Gin ttc att Phe Ile cct Pro gcg Ala atc Ile tat Tyr gg C Gly 75 ga t Asp ga a Glu c cg Pro t gc Cys ctt Leu 60 gag Glu cac His gtc Val1 cgt Arg t cg Ser atc Ile cac His atc Ile atg Met ggc Giy ~30 at t Ile gcc Ala atc Ile gct Ala cgc Arg 15 ttc Phe ctg Leu cac His acc Th r gac Asp 95 tac Tyr ctt Leu gag Giu ga t Asp gcg Al a 80 acg Thr 1 cca Pro ttc Phe acc Thr cca Pro 65 cag Gin gat Asp gga att Gly Ile tta ggc Leu Gly 35 ttg gac Leu Asp 5o ctt gat Leu Asp tgg att Trp Ile tac acc Tyr Thr ccg Pro 20 gat Asp ggt Gly t ac Tyr t cc Ser gat Asp 100 t tc Phe ctc Leu qaa Giu a cc Thr aac As n tt t Phe 163 211 259 307 355 403 451 tat acc tgg atc ggc qcg gaa tcc tcc gaa acc cgt gcg gcc aag aag Tyr Thr Trp Gly Ala Glu Ser Glu Thr Arg Ala Ala Lys Lys 115 WO 01/00804 cat ctg cag acc cac gcc ggc atg ccc aag acg cac atg aac gcg caa His Leu Gin Thr His Ala Gly Met Pro Lys Thr His Met Asn Ala Gin 120 125 130 ggt tat tgg aac aag ggc aga gcc atg qgt aaa agc aat taaaagattt Gly Tyr Trp Asn Lys Gly Arg Ala Met Gly Lys Ser Asn 135 140 145 ttgcttatcg acg <210> 200 <211> 146 <212> PRT <213> Corynebacteriun glutamicum <400> 200 Val Gly Asp Ala Leu Arg Gly Arg Gly Lys Pro Giu Val Met Arg Tyr 1 5 10 Pro Gly Ile Pro Phe Ala Ile Pro Asp Pro Ala Pro Arg Gly Phe Leu 25 Phe Leu Gly Asp Leu Thr Ser Tyr Pro Ala Ile Cys Ser Ile Leu Glu 40 Thr Leu Asp Gly Glu Ile Pro Ala Thr Ala Tyr Leu Ile Ala His Asp 55 Pro Leu Asp Tyr Thr Phe Asp Phe Pro Gin Gly Glu His Ile Thr Ala 70 75 Gin Trp Ilie Ser Asn Glu Gin Ser Phe Ile Asp His Ile Ala Asp Thr 90 Asp Tyr Thr Asp Phe Tyr Thr Trp Ile Gly Ala Giu Ser Ser Glu Thr 100 105 110 Arg Ala Ala Lys Lys His Leu Gin Thr His Ala Giy Met Pro Lys Thr 115 120 125 His Met Asn Ala Gin Giy Tyr Trp Asn Lys Giy Arg Ala Met Gly Lys 130 135 140 Ser Ash 145 <210> 201 <211> 736 <212> DNA <213> Corynebacterium giutamicum <2 <221> CDS <222> (736) PCT/IBOO/00922 499 548 561 WO 01/00804 <223> FRXA00993 <400> 201 gctgagctag tgcttttgcg acacacctct tgcgaatgtt PCT/IBOO/00922 gattaggtta ggcaaqccat atttacaggg tgttgtqaaa gcataaggga gcaaggaaac atg ggc aag gga ttt Met Gly Lys Gly Phe ace 2Thr acc Thr cat His etg Leu cge Arg ctg Leu a cg Thr at t Ile Gly gac Asp 150 9gC Gly acg Th r t cc Ser cgt Arg gcc Ala get Ala cgc Arg ccg Pro gat Asp 135 ggt Gly gct Al a gga Gly gag Glu ctg Leu t ac Tyr ttt Phe tgc Cys ttc Phe 120 ctc Leu gaa Gl u at t Ile aaa Lys a cg Thr tgg Trp acc Thr gtg Val1 gag Glu 105 gcc Ala acc Th r atc Ile ttg Leu ace Thr ct g Leu ttc Phe ttg Leu ct g Leu gcc Ala ate I le t ct Ser ect Pro ace gtc Thr Val gtg ate Val Ile ctc aac Leu Asn ccg cac Pro His 60 ace aac Thr Asn 75 eac gag His Giu ggg gaa Gly Glu eea gat Pro Asp tac cca Tyr Pro 140 gcg ace Ala Thr 155 ttt ccc Phe Pro( atg Met a at As n acg Thr 45 gag Glu gtg Val ccg Pro age Ser cca Pro 125 9gg Al a gg ~Ia :ag i1n 9gC Gly ga e Asp 30 ga a Giu age Ser gat Asp ctg Leu ct g Leu 110 geg Ala ate Ile tat Tyr ggc Gly gtg aaa Val Lys 15 ege atg Arg Met ggt gaa Gly Glu cga cet Arg Pro gcc gat Ala Asp 80 ggg ec Gly Pro 95 gaa gte Giu Val ccg egt Pro Arg tgC teg Cys Ser ctt ate Leu Ilie 160 gag cac Glu His 175 1 teg cat Ser His gtg ace Val Thr gte ccc Val Pro gga aag Gly.Lys gcc ggt Ala Gly gee teg Ala Ser atg cgc Met Arg ggc ttc Gly Phe 130 att ctg Ile Leu 145 gee cac Ala His ate ace Ile Thr ate Ile at t Ile ggc Gly etc Leu ace Thr qcg Ala tac Tyr 115 ett Leu gag Giu gat Asp gcg Al a gee Ala 20 eat His ga t Asp tac Tyr tt t Phe t gg Trp 100 cca Pro ttc Phe ace Thr c ea Pro ca g Gin 180 ace Thr ttt Phe t gg Trp eaa Gin ga c Asp geg Al a gga Gly eta Leu ttg Leu ett Leu 165 tgg Trp 115 163 211 259 307 355 403 451 499 547 595 643 gat tac ace ttc gat Asp Tyr Thr Phe Asp 170 att tcc aac gaa caa tee tte att gat cac ate get gac aeg gat tac Ile Ser Asn Giu Gin Ser Phe Ile 185 His Ile Ala Asp Thr Asp Tyr 195 WO 01/00804 ace gat ttt tat acc tgg atc ggc gcg gaa tcc tce gaa acc cgt Thr Asp Phe Tyr Thr Trp Ile Gly Ala Glu Ser Ser Glu Thr Arg 200 205 210 PCTIBOO/00922 736 <210> 202 <211> 212 <212> PRT <213> Corynebacterium glutamicum <400> 202 Met Gly Lys Gly Phe Thr Gly Ala Ile
I
Ser ValI Val1 Gly Ala Al a Met Gly Ile 145 Ala Ile Ala His Thr Pro Lys Gly Ser Arg Phe 130 Leu His Thr Asp Ile Ala Ilie His Gly Asp Leu Tyr Thr Phe Ala Trp 100 Tyr Pro 115 Leu Phe Glu Thr Asp Pro Ala Gin 180 Thr Asp 5 Thr Phe Trp Gin Asp Aia Gly Leu Leu Leu 165 Trp Thr Thr Gly Lys 25 His Ser Glu Thr Leu Arg Leu Trp 55 Arg Ala Tyr Thr Leu Ala Phe Vai Thr Arg Cys Glu 105 Ile Pro Phe Ala 120 Gly Asp Leu Thr 135 Asp Gly Glu Ile 150 Asp Tyr Thr Phe Ile Ser Asn Glu 185 Leu Thr Leu Phe Leu Leu Al a Ile Se r Pro Asp 170 Gin Val1 Ile Asn His Asn Giu Giu Asp Pro 140 Thr Pro Phe Gly Asp GI u Ser Asp Leu Leu 110 Ala Ile Tyr Gly Asp 190 Tyr Thr Asp Phe Tyr Thr Trp Ile 200 Ala Glu Ser 195 Ser Glu Thr Arg 210 <210> 203 <211> 732 <212> DNA WO 01/00804 <213> Corynebacterium glutamicum <220> <221> CDS <222> (101)..(709) <223> RXA01051 <400> 203 tgcgacccaa gatactctcg ggcaagctct tegttgttcg PCT/IBOO/00922 ttaaagattt tgaggaaacc taacagtgaa cacacaggcc atccccctag ggttggccat atg tea ace ait cac Met Ser Thr Ile His gee tcc Ala Ser ccg cca Pro Pro tta ctg Leu Leu atg aca Met Thr gaa gca Glu Ala get gat Ala Asp atc gca.
Ile Ala aga ttc Arg Phe gtc acc Val Thr 135 tat tca Tyr Ser 150 gga ate Gly Ile caa aag Gin Lys te gcg Phe Ala ctt ctt Leu Leu eac eaa His Gin cea eca Pro Pro ctg ttc Leu Phe 105 aae cat Asn His 120 age etc Ser Leu gat gte Asp Val eag Gin gae Asp ttt Phe aaa Lys t ae Tyr att Ile atg Met cga Arg agt Ser gat Asp get Al a gaa Glu tee Ser agt Ser aga Arg 75 tgg Trp eea Pro tte Phe ate Ile gac Asp 155 eea Pro tea Ser t te Phe ege Arg 60 tee Ser tg Trp ttt Phe ccc Pro gaa Glu 140 ctg Leu eaa Gin gtg Vai 9gC Gi y 45 et t Leu ate Ile ggg Gly 9gg Giy t te Phe 125 gtt Val1 ttg Leu qtg Val aag Lys 30 gt g Val1 tet Ser gae Asp ect Pro ttt Phe 110 gta Val1 ctg Leu ttt Phe ccea Pro 15 aag Lys tae Tyr tta Leu tta Leu tgg Trp 95 tte Phe gaa Giu eaa Gin a at Asn eae His age Ser etg Leu 9ge Gly gag Giu 80 aee Thr etg Leu ace Thr tgg Trp aeg Thr 160 1 ggt Gly tte Phe gtg Val1 gga Gi y et t Leu aae Asn tae Tyr ate Ile gt g Val1 145 ate Ile tc Ser aat As n ctg Leu etg Leu tte Phe act Thr aaa Lys ct g Le u 130 ttt Phe ggc Giy cac His gee Ala ctt Leu tgg Trp aae Asn ttt Phe atg Met 115 ttt Phe get Ala gga Gly eat His 20 tct Ser gtg Val aae Asn ggC Gly gge Gly 100 ct e Le u gee Ala att Ile etc Leu gee Al a t ct Ser atg Met aca Thr ttt Phe aac As n egt Arg age Ser gga Gly att Ile 165 gte Val 163 211 259 307 355 403 451 499 547 595 643 gga gca City Ala tee gta gca geg ett gtc teg ett aaa tee tee aag gta Ser Val Ala 170 Ala Leu Val Ser Lys Ser Ser Lys Val 180 WO 01/00804 PCT/IBOO/00922 agc gga atc atc atg ggc ggt tca cta tct gtg atg gcg atg atg atg 691 Ser Gly Ile Ilie Met Gly Gly Ser Leu Ser Val Met Ala Met Met Met 185 190 195 tat tca agt ttt atc gcc tagaaggttt cagcagttcc gct 732 Tyr Ser Ser Phe Ilie Ala 200 <210> 204 <211> 203 <212> PRT (213> Corynebacterium glutamicum <400> 204 Met Ser Thr Ile His Ala Ser Gly Ile Gin Ala Pro Gin Val Pro His 1 Giy Phe ValI Gly Leu Asn Tyr Ile Val1 145 Ile Ser Met Se r Asn Leu Leu Phe Thr Lys Leu 130 Phe dly Ser Al a pis Ala Leu Trp As n Phe Met 115 Phe Al a Giy Lys Met 195 His Se r Val1 Asn Gly Gly 100 Leu Ala Ile Leu Val 180 Met 5 Al a Se r Met Thr Phe Asn Arg Ser Gly Ile 165 Val Met Pro Le u Met Glu 70 Ala Ile Arg Val1 Tyr 150 Gly Ser Tyr Pro Leu Thr 55 Ala Asp Ala Phe Thr 135 Ser Ala Gi y Ser Gin Phe 40 Leu His Pro Leu Asn 120 Ser Asp Ser Ile Ser 200 Lys 25 Al a Leu Gin Pro Phe 105 His Leu Val Val1 Ile 185 Phe 10 Asp Phe Lys Tyr Ile 90 Met Arg Ser Asp Ala 170 Met Ile Giu S er Ser Arg 75 Trp Pro Phe Ile Asp 155 Al a Gi y Ala Ser Phe Arg Ser Trp Phe Pro Glu 140 Leu Leu Giy Val Lys Gly Val Leu Ser Ile Asp Gly Pro Giy Phe 110 Phe Vai 125 Val Leu Leu Phe Val Ser Ser Leu 190 Lys Tyr Leu Leu Trp Phe Glu Gin Asn Leu 175 Ser Ser Leu Gly Glu Thr Leu Th r Trp, Thr 160 Lys Val1 <210> 205 WO 01/00804 <211> 1359 <212> DNA <213> Corynebacteriun glutamicum <2 <221> CDS <222> (1336) <223> RXN01873 <400> 205 ccgtcgttgc ccatggtcac agcctacatg cacaaagtga PCT/IBOO/00922 atcaaaaaca gctatttcta acattttaet aatatttgct gttggcgcat gatgaactcc atg agc caa gca ata Met Ser Gin Ala Ile gat Asp gag Glu gc Ala ccc Pro acg Thr t eg Ser etc Leu att Ile Gly a ag Lys age S er cga Arg ggt Gly ace Thr gt g Val1 ata Ile acg Thr act Thr act Thr 135 gat Asp aag Lys gga Gi y ct t Leu atg Met t cg Ser ctt Leu t tg Leu gct Ala 120 cca Pro at t
TIP
gte Val1 aca Thr get Al a a cg Thr get Al a tcg Se r gcc Al a 105 etc Leu g cg Ala ggg Gly gag Glu ege Arg get Ala gaa Glu acg Thr gag Glu ate Ile ate Ile gtg Val1 cat His gca Ala aat Asn tte Phe gag Glu act Thr 75 aaa Lys ate Ile ctg Leu geg Al a gcg Ala eac His tac Tyr aat Asn ttg Leu 60 gga Gly ttt Phe gtg Val etc Leu atg Met 140 atg Met gaa Glu aag Lys ggt Giy 45 gga Gly atg Met ggt Gly gga Gi y aga Arg 125 ace Thr gga Gly ggc eac Gly His 15 ege get Arg Ala 30 ett tat Leu Tyr att aeg Ile Thr ttg geg Leu Ala ege ggt Arg Gly 95 tta att Leu Ile 110 ggt etc Gly Leu tgg ttg Trp Leu att. tac Ile Tyr ga a Glu gt g Val1 tge Cys ccc Pro etg Leu 80 egg Arg ttg Leu ea a Gin tet Ser ate Ile 1 9gc Gi y ttt Phe acg Thr act Thr 65 tgt Cys gt g Val ceg Pro ggt Gly gag Glu 145 geg Al a cac His gcg Ala ca g Gin 50 gag Glu att.
Ile ct g Leu ett Leu geg Ala 130 gaa Glu 9ga Gly ga a Glu atg Met 35 gea Al a tee Ser gt t Val aca Thr gte Val 115 ctg Leu att Ile aa t Asn ggc Gly 20 ctg Leu ttg Leu geg Ala ceg Pro att Ile 100 ccc Pro ctt Leu cae His act Th r ate Ile gee Ala ett Leu ctg Leu geg Al a tea, Ser aat Asn get Al a c Pro gtc Val1 165 163 211 259 307 355 403 451 499 547 595 643 150 155 gge ggg etc act gga egt atg att. ccg geg gga eta ctt gaa gta. act WO 01/00804 WO 0100804PCT/IBOO/00922 Gly Gly Leu Thi cat Hi.- Gi aag Lys Cg9 Arg 230 ggt Gly cag Gin ct g Leu atc Ile tcg Ser 310 ctg Leu qga Gly atg Met tct Se r tgc TrE gta Val aat Asn 215 aat Asn act Thr ttt Phe gcc Al a ggc Gly 295 atg Met ttt Phe tgg Trp tat Tyr gga Gly caa aac Gin Asn 185 atc atg Sle Met 200 *atc aat Ile Asn cct cgt *Pro Arg ttt gtg Phe Val ggg ctq Gly Leu 265 gqg ace Gly Thr 280 aat ggg Asn Gly gca ctg Ala Leu gtg ttt Val Phe atc gga Ile Gly 345 ttg ttc Leu Phe 360 ttc gcg Phe Ala
GI
174 gc Al~ qtc Va~ ct q Let ttc Leu t cg Ser 250 agt S er t gg Trp tca Ser a tg Met ace Thr 330 ate Ile tgt ttt y 0 Arg Met Ile Pro Ala Gly Leu Leu Glu Val Thr 175 180 actc a Let I gtc L Val Scgc Arg 9g Ala 235 ctg Leu gaa Glu agt Ser a cg Thr 9g9 Gly 315 gcg Al a atc Ile tat Tyr a cg ;ctg gga agt xLeu Gly Ser 190 ttg ctt ccc -Leu Leu Pro 205 *cat gag att His Glu Ile 220 Ittg ctt ttt Leu Leu Phe tac aac tat Tyr Asn Tyr gtg ctq gtt Val Leu Val 270 tce acc cag Ser Thr Gin 285 gtt att ttc Val Ile Phe 300 att aat aat Ile Asn Asn gca ttt ttc Ala Phe Phe gca acg aag Ala Thr Lys 350 tac qtq gga Tyr Val Gly 365 cat ttg ccg His Leu Pro 380 tct Ser aag Lys t cg Ser ggt Gly ttg Leu 255 ggt GI y gcg Ala ttg Leu ttg Leu gca Al a 335 ga t Asp t cc Ser L gg rrp atc Ile cag Gir gcg Ala act Thr 240 ggt Gly gcg Ala ggt Gly agt Ser tgg Trp 320 ctg Leu cgc Arg t cg Ser ttg Leu gct Ala cgg Arg Iatg Met 225 gcg Ala ttc Phe gtg Val1 gcg Ala ctg Leu 305 gt c ValI cat His gcg Ala gtg Val gcgI Ala 385 9c9 Ala aaa Lys 210 gct Ala ttt Phe cgc Arg ttc Phe ttg Leu 290 acg Thr acg Thr tecc Ser gaa Glu at t Ile 370 ttc Phe ct g Leu 195 ttc Phe gct Ala ttg Leu atg Met at c Ile 275 agg Arg atg Met ttg Leu a gt S er gee Al a 355 ggt Gly att Ile ate Ile cag Gin cat His ggc Gly att Ile 260 at g Met gag Giu atc Ile gtt Val gct Ala 340 tee Ser tgg Trp 99c Gly ttc Phe ccg Pro tgg Trp atg Met 245 ga t Asp tat Tyr a ag Lys gcg Ala gcc Ala 325 tcg Se r agc Ser gt t Val1 tgg rrp 691 739 787 835 883 931 979 1027 1075 1123 1171 1219 1267 1315 Phe Thr 375 ttg att ctg ctt ctt tgc gga gtg ctg gcg att tgt gtg acg ctg gca Leu Ile Leu Leu Leu Cys Gly Val Leu Ala Ile Cys Val Thr Leu Ala WO 01/00804 PCT/IB00/00922 390 395 400 405 agg ctt gcc cgc aac gcc aat taatacgagt ttgtccgtgt tta Arg Leu Ala Arg Asn Ala Asn 410 <210> 206 <211> 412 <212> PRT <213> Corynebacterium glutamicum <400> 206 Met Ser Gin Ala Ile Asp Ser Lys Val Glu Ala His Glu Gly His Glu 1359 1 Gly His Phe Ala Thr Gin Thr Glu Cys Ile Val Leu Pro Leu Gly Ala 130 Glu Glu 145 Ala Gly Leu Leu Ala Ala Arg Lys 210 Glu Met Ala Ser Val Thr Val 115 Leu Ile Asn Glu Leu 195 Phe Gly Leu Leu Ala Pro Ile 100 Pro Leu His Thr Val 180 Ile Gin 5 Ile Ala Leu Leu Ala Ser Asn Ala Pro Val 165 Thr Phe Pro Glu Ala Pro Thr 70 Ser Leu Ile Gly Lys 150 Gly His Gly Lys Arg Gly Thr 55 Val Ile Thr Thr Thr 135 Asp Gly Trp Val Asn 215 Gly Leu 40 Met Ser Leu Leu Ala 120 Pro Ile Leu Gin Ile 200 Ile Thr Ala Thr Ala Ser Ala 105 Leu Ala Gly Thr Asn 185 Met Asn 10 Arg Ala Glu Thr Glu 90 Ile Ile Val His Gly 170 Ala Val Leu Asn Tyr Phe Asn Glu Leu Thr Gly 75 Lys Phe Ile Val Leu Leu Ala Met 140 Ala Met 155 Arg Met Leu Leu Val Leu Arg His 220 Lys Gly Gly Met Gly Gly Arg 125 Thr Gly Ile Gly Leu 205 Glu Ala Tyr Thr Ala Gly Ile Leu Leu Tyr Ala 175 Ser Lys Ser Val Cys Pro Leu Arg Leu Gin Ser Ile 160 Gly lle Gin Ala Met Ala 225 Ala His Trp Asn Pro Arg Leu Leu Leu Phe Gly WO 01/00804 WO 0100804PCT/IBOO/00922 Ala Phe Leu Gly met Gly Thr Phe Val Ser Leu Tyr Asn Tyr Leu Gly 245 250 255 Phe Arg Met Ile Asp Gin Phe Gly Leu Ser Glu Val Leu Val Gly Ala 260 265 270 Val Phe Ilie Met Tyr Leu Ala Gly Thr Trp, Ser Ser Thr Gin Ala Gly 275 280 285 Ala Leu Arg Glu Lys Ile Gly Asn Gly Ser Thr Val Ile Phe Leu Ser 290 295 300 Leu Thr Met Ile Ala Ser Met Ala Leu Met Giy Ile Asn Asn Leu Trp 305 310 315 320 Val Thr Leu Val Ala Leu Phe Val Phe Thr Ala Ala Phe Phe Ala Leu 325 330 335 His Ser Ser Ala Ser Gly Trp Ile Gly Ile Ile Ala Thr Lys Asp Arg 340 345 350 Ala Giu Ala Ser Ser Met Tyr Leu Phe Cys Tyr Tyr Val Gly Ser Ser 355 360 365 Vai Ile Gly Trp Val Ser Giy Phe Ala Phe Thr His Leu Pro Trp, Leu 370 375 380 Ala Phe Ile Giy Trp Leu Ilie Leu Leu Leu Cys Gly Val Leu Ala Ile 385 390 395 400 Cys, Val Thr Leu Ala Arg Leu Ala Arg Asn Ala Asn 405 410 <210> 207 <211> 1215 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> (1192) <223> FRXA01873 <400> 207 ccgtcgttgc ccatggtcac agcctacatg cacaaagtga atcaaaaaca gctatttcta acattttact aatatttgct gttggcgcat gatgaactcc atg agc caa gca ata 115 Met Ser Gin Ala Ile 1 gat agc aag gtc gag gca cac gaa ggc cac gaa ggc cac gaa ggc atc 163 Asp Ser Lys Val Glu Ala His Glu Gly His Glu Gly His Giu Gly Ile 15 gag cga gga aca cgc aat tac aag cgc gct gtg ttt gcg atg ctg gcc 211 WO 01/00804 WO 0100804PCT/1BOO/00922 Glu Arg Gly Thr Arg Asn Tyr Lys Arg Ala Val Phe Ala Met Leu Ala
C
Ala
CCC
Pro acg Thr t cg Ser ctc Leu att Ile Gly aag Lys 150 ggc Gi y cat His ggc Gly aag Lys cgg gg t Gi y acc Thr gtg Val1 ata Ile a cg Thr act Thr act Thr 135 gat Asp ggg Gly t gg Trp gta Val aat As n 215 aat ctt Leu atg Met tcg Ser ctt Leu ttg Leu gct Ala 120 cca Pro att Ile ctc Leu caa Gin atc Ile 200 atc Ile cct gct Ala acg Th r gct Al a t cg Se r
C
Ala 105 ctc Leu gcg Ala ggg Gi y act Thr aac Asn 185 atg Met aat Asn cgt *gct Ala Igaa Glu acg Thr gag Glu atc Ile atc Ile gtg Val1 cat His gga Gly 170 gca Ala gtg Val Ct g Leu t tg ttc Phe gag Giu act Thr 75 aaa Lys atc Ile Ct 9 Leu gcg Al a gcg Ala 155 cgt A-rg Ctg Leu gtg Val cgc Arg gCg Ala 235 *aat ggt Asn Gly 45 ttg gga Leu Gly 60 gga atg Gly Met ttt ggt Phe Gly gtg gga Val Gly ctc aga Leu Arg 125 atg acc Met Thr 140 atg gga Met Gly atg att Met Ile ctg gga Leu Giy ttg ctt Leu Leu 205 cat gag His Giu 220 ttg ctt Leu Leu ctt Leu att Ile ttg Leu cgc Ar g tta Leu 110 ggt Gly t gg Trp att Ile ccg Pro agt Ser 190 ccc Pro att Ile ttt Phe tat Tyr acg Th r gcg Al a ggt Gly 95 att Ile ct C Leu ttg Leu tac Tyr gcg Ala 175 t Ct Ser aag Lys tcg Ser 99 t Gly tgc Cys I ccc Pro ctg Leu 80 cgg Arg ttg Leu caa Gin tct Ser atc Ile 160 gga Gly atc Ile cag Gin gcg Al a act Thr 240 acg Thr act Th r tgt Cys gtg Vai Ccg Pro ggt Gly gag Glu 145 gcg Al a ct a Leu gct Ala C9g Arg atg Met 225 gcg Ala cag Gin gag Giu att Ile ctg Leu ctt Leu gcg Al a 130 gaa Gi u gga Gly ctt Leu gcg Ala aaa Lys 210 gct Al a ttt Phe gca Ala tcc Ser gtt Val1 aca Thr gt C Val1 115 ct 9 Leu att Ile aat Asn gaa Giu ctg Leu 195 ttC Phe gc t Al a ttg Leu ttg Leu gcg Ala CCg Pro att.
Ile 100 ccc Pro ctt.
Leu cac His act Thr gta ValI 180 atc Ile ca 9 Gin cat His gyc Gly ctt Leu ct g Leu gcg Ala tca Ser aat Asn gct Ala
CCC
Pro gtC Val 165 act Thr ttC Phe ccg Pro tgg Trp at g Met 245 259 307 355 403 451 499 547 595 643 691 739 787 835 Arg Asn Pro Arg Leu 230 act ttt gtg tcg ctg tac aac tat ttg ggt ttc cgc atg att. gat Thr Phe Val Ser Leu Tyr Asn Tyr Leu Gly Phe Arg Met Ile Asp WO 01/00804 PCTABOO/00922 250 255 260 eag ttt ggg etg agt gaa gtg ctg gtt ggt gcg gtg tte atc atg tat 931 Gin Phe Gly Leu Ser Glu Val Leu Val Gly Ala Val Phe Ile Met Tyr 265 270 275 etg gee ggg ace tgg agt tce ace eag gcg ggt gcg ttg agg gag aag 979 Leu Ala Giy Thr Trp Ser Ser Thr Gin Ala Gly Ala Leu Arg Glu Lys 280 285 290 atc ggc aat ggg tca acg gtt att ttc ttg agt etg acg atg atc gcg 1027 Ile Gly Asn Gly Ser Thr Val Ile Phe Leu Ser Leu Thr Met Ile Ala 295 300 305 tcg atg gca etg atg ggg att aat aat ttg tgg gte acg ttg gtt gee 1075 Ser Met Ala Leu Met Gly Ile Asn Asn Leu Trp Val Thr Leu Val Ala 310 315 320 325 etg ttt gtg ttt acc gcg gca ttt ttc gca etg cat tcc agt get tcg 1123 Leu Phe Val Phe Thr Ala Ala Phe Phe Ala Leu His Ser Ser Ala Ser 330 335 340 gga tgg ate gga ate ate gea aeg aag gat cgc geg gaa gee tee age 1171 Gly Trp Ilie Gly Ile Ile Ala Thr Lys Asp Arg Ala Giu Ala Ser Ser 345 350 355 atg tat ttg tte tgt gaa tao taggatccte ggtgattggt tgg 1215 Met Tyr Leu Phe Cys Glu Tyr 360 <210> 208 <211> 364 <212> PRT <213> Corynebaeteriun glutanijeum <400> 208 Met Ser Gin Ala Ile Asp Ser Lys Vai Glu Ala His Glu Gly His Glu 1 5 10 Gly His Giu Gly Ile Giu Arg Gly Thr Arg Asn Tyr Lys Arg Ala Val 25 Phe Ala Met Leu Ala Ala Gly Leu Ala Ala Phe Asn Giy Leu Tyr Cys 40 Thr Gln Ala Leu Leu Pro Thr Met Thr Glu Glu Leu Gly Ile Thr Pro 55 Thr Glu Ser Ala Leu Thr Val Ser Ala Thr Thr Gly Met Leu Ala Leu 70 75 Cys Ilie Val Pro Ala Ser Ile Leu Ser Giu Lys Phe Gly Arg Gly Arg 90 Val Leu Thr Ile Ser Leu Thr Leu Ala Ile Ile Val Gly Leu Ile Leu 100 105 110 WO 01/00804 Pro Leu Val Pro 115 PCT/IBOO/00922 Asn Ile Thr Ala Leu Ile Leu Leu Arg Gly Leu Gin 120 125 Gly Gin 145 Ala Le u Ala Arg Met 225 Ala Phe Val1 Ala Leu 305 Val His Ala 130 Glu Gi y Leu Ala Lys 210 Al a Phe Arg Phe Le u 290 Thr Thr Ser Leu Ile Asn Glu Leu 195 Phe Ala Leu Met Ile 275 Arg Met Leu Ser Leu His Thr Val1 180 Ile Gin His Gly Ile 260 Met Glu Ile Val Ala 340 Al a Pro Val 165 Thr Phe Pro Trp Met 245 Asp T yr Lys Al a Ala 325 Ser Gly Lys 150 Gly His Gly Lys Arg 230 Giy Gin Leu Ile Ser 310 Len Gly Thr 135 Asp Gi y Trp Val Asn 215 As n Thr Phe Ala Gly 295 Met Phe rrp Pro Ile Leu Gin Ile 200 Ile Pro Phe Gly Gly 280 Asn Aia Val1 Ile Ala Giy Thr Asn 185 Met Asn Arg Val Leu 265 Thr Gly Len Phe Gly 345 Vai His Gi y 170 Al a Val1 Leu Leu Ser 250 Ser Trp Ser Met Th r 330 Ile Ala Met 140 Ala Met 155 Arg Met Leu Len Val Leu Arq His 220 Ala Leu 235 Len Tyr Gin Vai Ser Ser Thr Val 300 Gly Ile 315 Ala Ala Ile Ala Thr Trp Gly Ile Ile Pro Gly Ser 190 Leu Pro 205 Glu Ile Len Phe Asn Tyr Leu Val 270 Thr Gin 285 Ile Phe Asn Asn Phe Phe Thr Lys 350 Leu Tyr Ala 175 Ser Lys Ser Gly Len 255 Gly Ala Leu Len Ala 335 Asp Ser Ile 160 Giy Ile Gin Al a Th r 240 Gly Ala Gly Ser Trp 320 Leu Arg Ala Gin Ala 355 Ser Ser Met Tyr Leu 360 Phe Cys Giu Tyr <210> 209 <211> 1572 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS WO 01/00804 (222> (1549) <223> RXN00034 <400> 209 taaattttgt ggcactcccc acatttctai caatctatag PCT/IBOO/00922 aaagtatgac ttaaagtcqa ttttgcaaqi ttctatagat tgatagaaaa qggagtttag atg tct tac aca tci Met Ser Tyr Thr Ser tt Phe aca Thr gca Al a gcc Al a gca Ala aac Asn a cc Thr
C
Al a act Thr ggc Gly 150 tt aaa Lys ttt Phe act Thr gcc Ala gat Asp atc Ile ca a Gin atc Ile gac Asp 135 acc Thr ggt ggc Gi y tgg Trp gat Asp gcg Ala gt c Val1 ci g Leu atg Met aig Met 120 cgc Arg gga Gi y igg gat Asf ctt Leu ta Leu tta Phe gga Gi y gig Val 105 t ci Ser ca a Gin tic Phe aga -gat Asp iii Phe 999g Gly tt Phe ggc Gly i ci Ser atc Ile gca Ala cga Axrg tgc Cys gga Gly 170 aaa Lys gct Ala aig Met igt Cys cga Arg 75 ctc Leu a cc Thr icc Ser gca Al a gcg Al a 155 aic gcc Ala cag Gin agc Se r gga Gly 60 gia ValI cic Leu ggc Gly cia Leu gtc Val 140 ct Leu tic ci c Let t ca Ser gat Asp 45 a ca Th~r cga Arg aic Ile cga Arg gca Ala 125 tcc Ser ttc Phe jcc atc Ile acc Thr ggc Gly ttt Phe aic Ile gCC Ala gt Val 110 tie Leu at Ile gcg Ala ctc Leu 9gc Gly 15 cia Leu acc Thr etc Ile atg Met acg Thr 95 ci c Leu gii Val i gg T rp ~g Gly :ys 175 eta Ile aai Asn atg Met gic Val1 aig Met 80 gca Al a caa Gin aag Lys icc Ser ct Leu 160 gcg Ala 1 gt Val a ic Ile ac Asn gca Ala at i Ile a cg Thr gga Gly a ca Thr at Ile 145 gt t Val1 etc Ile ita Leu ggc Gly aia Ile gcc Al a ggc Gly act Thr ctg Leu tai Tyr 130 gqt Gly gta Val1 gic Val1 ice ISer cca Pro gct Al a ggc Gly a ac Asn ici Ser gce Ala 115 igg .Trp tca Se r gca Ala icc Ser gi i Val1 get Asp gtc Val1 ggc Gly atc Ile iia Leu 100 gca Ala tie Leu igg Trp a gc Ser etc Ile 180 ctc Leu atg Met gig Val1 atc Ile ct t Leu gcc Al a gcg Al a ggi Gly ggi Gly ccc Pro 165 gitt Val1 163 211 259 307 355 403 451 499 547 595 643 Phe Gly Trp Arg Ilie Phe Ala ait gcc cti acc cgc cac etc ccg icc cgi ccg Ser Arg Pro Ile Ala Leu 185 Thr Arg His Ile gci caa icc Ala Gin Ser 195 WO 01/00804 WO 0100804PCTIIBOO/00922 att gge Ile Gly gtt eta Val Leu 215 acg cac Thr His 230 gca gtt Ala Val ttc aac Phe Asri t att Phe Ile cag caa Gin Gin 295 ate ggc Ile Gly 310 gee atg Al a Met ttg gta Leu Val tca aeg Ser Thr gg cetc Giy Leu 375 ctt ccc Leu Pro 390 atg cat ttc Met 200 t ct Ser tgg Trp tc Phe ctt Leu atg Met 280 atg Met ttc Phe cag Gin geg Ala t ae Tyr 360 gga Gly ma L-ys His ett Leu atg Met gte Val1 ttc Phe 265 age Se r gga Gi y gca Ala aaa Lys ace Thr 345 atc Ile etc Leu gac Asp Leu gaa Git ac Thr ttc Phe 250 aaa Lys gct Ala t gg T rp gee Ala gtt Val1 330 gcg Al a gt c Val1 ttc Phe cgt Arg gat Asp tg Leu tgg Trp 235 att Ile gac Asp act Th r ggt Gly ttt Phe 315 ggC Gi y acc Thr atc Ile gcc Ala ace Thr 395 t gg Trp ttt Phe 220 act Thr gaa Glu cac His gge Gly gtC Val1 300 gtc Val1 gee Ala gee Ala tee Ser acc rhr 380 9gC ;ly agt Ser 205 at Ile etc Leu cgc Arg gCC Ala gga Gly 285 icc Se r ate Ile cga Arg etc Leu etc Leu 365 eca.
Pro get Ala gge Giy *ace Thr ett *Leu ate Ile tiC Phe 270 gi ta Val1 cea Pro ct t Leu gea Ala eta Leu 350 gee Aia gte Val ggt Gly ate Ile caa Gin gee Al a gee Al a 255 age Ser gtt Val1 aea Thr te Phe gtg Val1 335 atg Met gge Giy rhr gca Ala ate Ile ggt Gly gt t Val 240 age Ser ggt Gly gee Ala ate Ile at t Ilie 320 ate Ile ate Ile te Phe gat Asp ggt Giy 400 gt Val ga a Glu 225 t ct Ser tgg Trp geg Ala gt t Val1 teg Ser 305 cga Arg ate Ile ace Thr tee Ser aet Thr 385 gta ValI ett.
Leu 210 tea Ser ttg Leu cc a Pro ace Thr gte Val1 290 gga Gly gtt Val1 ace Thr geg Ala Ct t Leu 370 9gg Ala tie Phe gee Al a ct Leu aea Tb r gtt Val1 ate Ile 275 atg Met etc Leu gga Gly get Ala gte Va 1 355 tat Tyr Ct Leu sag Lys etc Leu ggc Gly ttt Phe etc Leu 260 ace Thr t gg T rp ace Tb r gaa Glii gge Gly 340 age Se r ggc Gly gga Gly a tg Met a gt Ser t gg T rp eti Leu 245 gac Asp aac Asn gitt Val1 age Se r aag Lys 325 ate Ile gag Glu ett Leu aca Thr ice Ser 405 739 787 835 883 931 979 1027 1075 1123 1171 1219 1267 1315 1363 tet ice etc Ser Ser Leu ggc gca Gly Ala 410 gca etc gge ate Ala Leu Giy Ilie gea Ala 415 ate tee act ica gtg tte Ile Ser Thr Ser Val Phe 420 WO 01/00804 cic gca ctt cgc gac ggc acc tcc atc Leu Ala Leu Arg Asp Gly Thr Ser Ile 425 430 gga aca gtt tca ctt ggc atc aac gtt Gly Thr Val Ser Leu Gly Ile Asn Val 440 445 atc acc gca gca gtc ctt att cca aaa Ile Thr Ala Ala Val Leu Ile Pro Lys 455 460 acc agc atc acc ctt cct gag cca gct Thr Ser Ile Thr Leu Pro Glu Pro Ala 470 475 taaaacttca ccaggacaga. taa <210> 210 <211> 483 <212> PRT <213> Corynebacterium giutamicum gtc gca ctc gcc Val Ala Leu Ala 435 qca. aca gcc acc Ala Thr Ala Thr 450 aaa gtc tca caa Lys Val Ser Gin aaa atc Lys Ile PCT/IBOO/00922 1411 1459 1507 1549 1572 <400> 210 met Ser Tyr Thr Ser Phe Lys Gly Asp 1 Val1 Ile Asn Ala Ile Thr Gly Thr Ile 145 Leu Gly Ile Ala Gi y Thr Leu Tyr 130 Gly Val1 Asp ValI Gi y Ile Leu 100 Ala Leu Trp Thr Al a Ala Al a 70 Asn Tb r Al a Thr Gly 150 Phe Thr Al a 55 Asp Ile Gin Ile Asp 135 Thr Trp Leu 25 Asp Leu Ala Leu Val Phe Leu Gly Met Val 105 Met Ser 120 Arg Gin Gly Phe Asp 10 Phe Gly Phe Gly Ser Ilie Ala Arg Cys Lys Ala Leu Ile Ala Met Cys Arg 75 Leu Thr Ser Ala Ala 155 Gin Ser Ser Asp Gly Thr Val Arg Leu Ile Gly Arg Lea Ala 125 Val Ser 140 Leu Phe Thr Gly Phe Ile Al a Val1 110 Leu Ile Al a Gly Ile Lea Asn Thr Met Ile Val Met Met Thr Ala Leu Gin Val Lys Trp Ser Gly Lea 160 Val Val Ala Ser Val Vl Al Ser Phe Gly Trp Arg liPhAaLe Ile Phe Ala Leu Cys Ala 175 Ile Arg Val1 Glu 225 Ser Trp Ala Val Ser 305 Arg Ile Thr Se r Thr 385 Val1 Ser Asp Ala WO 01/00804 Val Ser Ile 180 Pro Ala Gin 195 Leu Ala Leu 210 Ser Leu Gly Leu Thr Phe Pro Val Leu 260 Thr Ile Thr 275 Val Met Trp 290 Gly Leu Thr Val Gly Giu Thr Ala Gly 340 Aia Val Ser 355 Leu Tyr Gly 370 Ala Leu Giy Phe Lys Met Thr Ser Val E 420 Val Ala Leu AD 435 Ala Thr Ala T 450 PCTIBOO/00922 Val1 Ser Se r Trp Leu 245 Asp Asn Val Se r Lys 325 Ilie ilu Leu [hr e r ~he la hr Ala~ Ile Val] Thr 2 30 Ala Phe Phe Gin Ile 310 Aia Leu S er Gly Leu 390 Se r Leu Gly I le Ile *Giy *Leu 215 *His Vai As n Ile Gin 295 Gly Met Val1 Thr Leu 375 Pro Ser Ala Thr Thr 455 Al Met 20(C Sez TrF Phe Leu Met 280 Met Phe Gin Al a Tyr 360 Gly Lys Leu Leu Val1 440 klia Leu 185 -His *Leu Met *Val IPhe 265 Ser Giy Ala Lys Thr 345 Ile Leu Asp Giy Arg 425 Ser Ala Thr Leu Giu Thr Phe 250 Lys Al a Trp Al a Val1 330 Al a Val Phe Arg Ala 410 Asp Leu Val1 Arc IAsj ILex.
Trp 235 Ile Asp Thr Gly Phe 315 Gly Thr Ile Ala Thr 395 Ala Gly Giy Leu His Trp Phe 220 Thr Glu His Giy Val 300 Val1 Ala Ala Se r Thr 380 Giy Leu Thr Ile Ile 460 Ile Se r 205 Ile Leu Arg Ala Gly 285 Ser Ile Arg Leu Leu 365 Pro Ala Gly Ser As n 445 Pro Pro 190 Gly Thr Leu Ile Phe 270 Val1 Pro Leu Aia Leu 350 Ala Vai Gly Ile Ile 430 Vai Lys Glu Ile Gin Ala Al a 255 Se r Vali Thr Phe Val 335 Met Gly Thr Ala Ala 415 Asn Val A~la Se r Ile Giy Val1 240 Se r Giy Ala Ile Ile 320 Ile Ile Phe Asp Gi y 400 Ile Ser Phe Ala Gly 465 Lys Val Ser Gln Ser Ile Thr Leu Pro 475 Giu Pro Ala Ile WO 01/00804 PCTIIBOO/00922 Val Lys Ile <210> 211 <211> 1045 <212> DNA <213> Corynebacteriun glutarnicum <220> <221> CDS <222> (1045) <223> FRXA02273 <400> 211 taaattttgt ggcactcccc acatttctat caatctatag aaagtatgac ttaaagtcga ttttgcaagt ttctatagat tgatagaaaa gggagtttag atg tct tac aca tct Met Ser Tyr Thr Ser ttt aaa Phe Lys aca ttt Thr Phe gca act Ala Thr gcc gcc Ala Ala gca gat Ala Asp aac atc Asn Ile acc caa Thr Gin gcc atc Ala Ile ggC Gly t gg Trp gat Asp gCg Ala gtc Val1 ctg Leu atg Met atg Met 120 ga t Asp ctt Leu t ta Leu tta Leu ttt Phe gga Gly gtg Vai 105 tct Ser gat Asp ttt Phe ggg GI y ttc Phe ggC Gly t Ct Ser atc Ile gca Alia aaa Lys gc t Al a atg Met tgt Cys cga Arg 75 ctc Leu acc Thr tcc Ser gCC Al a cag Gin agc Se r gga Gly 60 gta Val1 ctc Leu ggc Gly cta Leu ctc Leu t ca Se r gat Asp 45 a ca Thr cga Arg atc Ile cga Arg gca Ala 125 a tc Ile acc Thr 30 ggc Gly t tt Phe atc Ile gcc Ala gtt Val 110 tta Leu ggc Gi y 15 ct a Leu acc Thr atc Ile atg Met acg Thr 95 ctc Leu gtt Val ata Ile aat Asn a tg Met gtc Val1 at g Met 80 gca Al a caa Gin aag Lys 1 gtt ValI atc Ile aac Asn qca Ala att Ile acg Thr gga Gly a ca Thr tta Leu ggc Gly ata Ile gcc Ala ggc Gly act Thr ctg Leu tat Tyr 130 tca Se r cca Pro gct Ala ggC Gly aac Asn t ct Ser gca Ala 115 tgg Trp gt t Val1 ga t Asp gtc Val ggC Gly a tc Ile tta Leu 100 gca Ala tta Leu ctc Leu atg Met gtg Val atc Ile ctt Leu gCC Ala gcg Ala ggt Gi y 115 163 211 259 307 355 403 451 499 act gac Thr Asp 135 cgc caa cga gca Arg Gln Arg Ala gtc Val 140 tcc att tgg tcc att ggt tca tgg qgt Ser Ile Trp, Ser Ile 145 Gly Ser Trp Gly WO 01/00804 PCTIBOO/00922 ggc acc gga ttc tgc gcg cit tic gcg ggt ctt git gta gca agc ccc 595 Gly Thr Gly Phe Cys Ala Leu Phe Ala Gly Leu Val Val Ala Ser Pro 150 155 160 165 ttt ggt tqg aga gga atc ttc gcc ctc tgc gcg atc gtc tcc atc gtt 643 Phe Gly Trp Arg Gly Ile Phe Ala Leu Cys Ala Ile Val Ser Ile Val 170 175 180 gct ait gcc ctt acc cgc cac atc ccg gaa tcc cgt ccg gct caa tcc 691 Ala Ile Ala Leu Thr Arg His Ile Pro Glu Ser Arg Pro Ala Gin Ser 185 190 195 att ggc atg cat itg gat tgg agi ggc aic atc git cit gcc ctc agt 739 Ilie Gly Met His Leu Asp Trp Ser Gly Ile Ile Val Leu Ala Leu Ser 200 205 210 gtt cta tct ctt gaa ttg itt att acc caa ggt gaa tca cii ggc tgg 787 Val Leu Ser Leu Giu Leu Phe Ile Thr Gin Gly Giu Ser Leu Gly Trp 215 220 225 acg cac tgg aig acc tgg act cic cit gcc gtt ict tig aca itt cit 835 Thr His Trp Met Thr Trp Thr Leu Leu Ala Val Ser Leu Thr Phe Leu 230 235 240 245 gca gtt tic gtc tic att gaa cgc aic gcc agc tgg cca gtt cic gac 883 Ala Val Phe Val Phe Ile Giu Arg Ile Ala Ser Trp Pro Val Leu Asp 250 255 260 tic aac cii tic aaa gac cac gcc ttc agc ggt gcg acc aic acc aac 931 Phe Asn Leu Phe Lys Asp His Ala Phe Ser Gly Ala Thr Ile Thr Asn 265 270 275 tic ati atg agc gct act ggc gga gia git gcc gtt gtc aig igg git 979 Phe Ilie Met Ser Ala Thr Gly Giy Val Val Ala Val Val Met Trp Val 280 285 290 cag caa atg gga tgg ggi gic icc cca aca aic icg gga cic acc agc 1027 Gin Gin Met Gly Trp Gly Val Ser Pro Thr Ile Ser Gly Leu Thr Ser 295 300 305 aic ggc tic gca gcc tit 1045 Ile Gly Phe Ala Ala Phe 310 315 <210> 212 <211> 315 <212> PRT <213> Corynebacterium giuianiicum <400> 212 Met Ser Tyr Thr Ser Phe Lys Gly Asp Asp Lys Ala Leu Ile Gly Ile 1 5 10 Val Leu Ser Val Leu Thr Phe Trp Leu Phe Ala Gin Ser Thr Leu Asn 25 WO 01/00804 WO 01/43804PCTIIBOO/00922 Ile Gly Pro Asp Met Ala Thr Asn Al a Ile Thr Gly Th r Ile 145 Val1 Ile Arg Val1 Glii 225 Ser Trp Ala Ile so Ala Gly Thr Leu Tyr 130 Gly ValI Val Pro Leu 210 Se r Leu Pro Thr Ala Gly Asn Se r Al a 115 Trp Ser Ala Ser Ala 195 Ala Leu Thr Val Ile 275 Val1 Gly Ile Leu 100 Ala Leu Trp Se r Ile 180 Gin Leu Gly Phe Leu 260 I'hr Val1 Ile Leu Ala Ala Gly GI y Pro 165 Val1 Ser Ser Trp Leu 245 Asp Asn Ala Al a 70 Asr Thr Ala Th r Gly 150 Phe Ala Ile Val1 Th r 230 Aa ?he Phe Ala Asp Ile Gin Ile Asp 135 Thr Gly Ile Gly Leu 215 His Val Asn Ile Gin 295 *Asp 40 Ala Val Leu Met Met 120 Arg Gly Trp Al a Met 200 Ser Trp Phe Leu Met 280 Met Leu Phe Gi y Val 105 Ser Gin Phe Arg Leu 185 His Leu Met Val1 Phe 265 Ser ;iy Leu Gly Met Ser Phe Gi y Ser 90 Ile Al a Arg Cys Gly 170 Thr Leu Glu Th r Phe 250 Lys Ala Trp Cys Arg 75 Leu Thr Ser Ala Al a 155 Ile Arg Asp Le u Trp 235 Ile Asp rhr 31 y Gly Val1 Leu Gly Leu Val1 140 Leu Phe His Trp Phe 220 Thr Glu His Gi y ValI 300 Asp Thr Arg Ile Arg Ala 125 Se r Phe Ala Ile Ser 205 Ile Leu Arg Ala Gly 285 Ser Phe Ile Ala Val1 110 Leu Ile Ala Leu Pro 190 Gly Thr Leu Ile Phe 270 lal Ile Met Thr Leu ValI T rp Gly Cys 175 Glu Ile Gin Al a Al a 255 Ser Val Thr Gly Thr Met Val Met Ala Gin Lys Ser Leu 160 Ala Ser Ile Gly ValI 240 Ser Gly Ala Ile Val Val Met Trp Val Gin 290 Ser Gly Leu Thr Ser Ile Gly Phe Ala Ala Phe 305 310 315 <210> 213 WO 01/00804 <211> 826 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> (826) <223> RXN03075 <400> 213 tgtgcaaaat tgcattcagg ctgaaaaatt cctaaaggga PCT/IBOO/00922 ctccgtccga ataattggaa agcccagaag aacagtcaac tcctagatta aaggataatc gtg gcg aaa ttc ctg Val Ala Lys Phe Leu tat Tyr gtc Val1 gcc Ala aeg Thr aca Thr acc Thr gag Giu cct Pro gag aag Lys t gg Trp aag Lys acc Th r t cg Ser ctc Leu gtt Val1 gt g Val1 gct Itta Leu etc Leu cca Pro atg Met gct Ala act Thr cgg Arg ttg Leu 120 cag 9gc Giy gtg Val1 acg Thr gag Giu ccc Pro ga t Asp gcg Al a 105 gct Ala ggt *tee Ser att Ile tcg Ser aag Lys act Thr cc t Pro act Thr gcg Ala gta acg Th r ctc Leui agt Ser atg Met ggt Gi y 75 gag Glu ggt Gly cag Gl n cct gcc Ala ata Ile agc Ser cag Gin 60 tct Ser gtt Val1 gtg Val1 ggt Gly geg tat ITyr ggt Giy ttc Phe 45 gag Glu gt C Val1 ggg Gly ctg Leu gtg Val 125 gag caa Gin atc Ile 30 t ct Ser cgt Arg gt C Val1 gct Ala aag Lys 110 gct aag aag Lys 15 a cg Thr atc Ile tt C Phe att Ile gaa Glu 95 gat Asp gct Ala aaa Lys acg Thr cct Pro cct Pro cag Gin 80 gta Val1 gct Al a ca g Gin t gg T rp ctg Leu ggt Gly ggt Gly gca Ala aac Asn ga t Asp atg Met ccg ttt Pro Phe Igcg ggg Ala Gly ctt gat Leu Asp tcg gat Ser Asp ccg gaa Pro Giu cag atg Gin Met tcc gtt Ser Vai 115 acc cca Thr Pro 130 gat att Asp Ile ate teg ctt gcg Leu Ala ctg tat Leu Tyr tct gtc Ser Val gat gca Asp Ala ggc aag Gly Lys ctt gat Leu Asp 100 gtg gat Vai Asp gee ctg Ala Leu gag tcg Glu Ser atg act Met Thr 165 163 211 259 307 355 403 451 499 547 595 ate gcc gca Glu Ala Gin Gly Val Pro Ala Glu 135 140 Lys Ile Ala act ace ggc Thr Thr Gly 160 att agt eca ctg agt gca Ile Ser Pro Leu Ser Ala 150 155 gat gag Asp Glu Ile Ile Ser ttt gat gca gat tct gee atg gat ata tee gca gag gat cgt gag aag WO 01/00804 Phe Asp Ala Asp Ser Ala Met Asp Ile 170 gte acc aat att ctt gat gaa tac gat Val Thr Asn Ile Leu Asp Glu Tyr Asp 185 190 tac aac ggc aac gtg ttt ggc gca get Tyr Asn Gly Asn Val Phe Gly Ala Ala 200 205 tct gag ctc ate ggc etg ctg gtg get Ser Glu Leu Ile Gly Leo Leu Val Ala 215 220 ttc ggt teg ttc atc get gec ggt atg Phe Gly Ser Phe Ile Ala Ala Gly Met 230 235 <210> 214 <211> 242 <212> PRT <213> Corynebacteriun glutamicum PCT/IBOO/00922 Al a gge cay ace Thr gte Val etg Leu 240) Asp Arg Glu Lys 180 etg act gtt gte Leo Thr Val Val 195 ttg gac atg ace Leo Asp Met Thr 210 ctt ate gtg ace Leo Ile Val Thr tet Ser 691 739 787 826 <400> 214 Val Ala Lys Phe Leu Tyr Lys Leu Gly Ser Thr Ala Tyr Gin Lys Lys 1 Trp Pro Leo Ala Gly Leu Gly Ser Ala Pro Asn Gin Asp Ser Met Thr 130 Phe Gl y Asp Asp Glu Met Val1 115 Pro Le u Leo Ser Asp Gly Le u 100 Val1 Ala 5 Al a Tyr Val Ala Lys Asp Asp Leu Val1 Ala Thr Thr 70 Thr di u Pro Glu Trp Lys Thr 55 Ser Leu Val Val Al a 135 Leo Val Ile Leu Ile Gly Ile Thr Thr Pro 40 Met Ala Thr Arg Leu 120 Gin 25 Thr Glu Pro Asp Ala 105 Ala Gly Ser Lys Thr Pro 90 Thr Al a Val1 Se r Met Gi y 75 Giu Gly Gin Pro Ser Gln Ser Val1 Val1 GI y Ala 140 Phe Giu Val Gly Leu Val 125 Giu Glu Ser Arg Val1 Ala Lys 110 Ala Lys Thr Ile Phe Ile Giu Asp Ala Ile Thr Pro Pro Gin Val1 Ala Gin Al a Gly 160 Ala Asp Ile Glu Ser Ile Ser Pro Leu Ser Ala Asp Ile Ile Ser Met Thr Phe Asp Ala Asp Ser Ala Met Asp Ile Ser Ala WO 01/00804 WO 0100804PCTIIBOO/00922 165 170 175 Glu Asp Arg Giu Lys Val Thr Asn Ile Leu Asp Glu Tyr Asp Asp Gly 180 185 190 Asp Leu Thr Val Val Tyr Asn Gly Asn Val Phe Gly Ala Ala Ala Thr 195 200 205 Ser Leu Asp Met Thr Ser Giu Leu Ile Gly Leu Leu Val Ala Ala Val 210 215 220 Val Leu Ile Val Thr Phe Gly Sei Phe Ile Ala Ala Gly Met Pro Leu 225 230 235 240 Ile Ser <210> 215 <211> 826 <212> DNA <213> Corynebacteriun glutarnicum <220> <221> CDS <222> (101) (826) <223> FRXA02907 <400> 215 tgtgcaaaat tgcattcagg ctgaaaaatt cctaaaggga agcccagaag aacagtcaac tcctagatta aaggataatc tat Tyr gtc Val1 gcc Al a acg Tb r aca Thr ac Thr ggC Gly gt q Val acg Thr gag Gi u ccc Pro ga t Asp acg gcc Thr Ala ctc ata Leu Ile agt agc Ser Ser atg cag Met Gin ggt tct Gly Ser 75 gag gtt Giu Val tat Tyr ggt Giy ttc Phe gag Giu gtc Val ggg Gly caa Gin atc Ilie 30 tct Ser cgt Arg gtc Val1 gct Al a aaa Lys acg Thr cct Pro cct Pro cag Gin 80 gta Val ctccgtccga ataattggaa gtg gcg aaa ttc ctg Val Ala Lys Phe Leu 1 tgg ccg ttt ctt gcg Trp Pro Phe Leu Ala ctg gcg ggg ctg tat Leu Ala Gly Leu Tyr ggt ctt gat tct gtc Gly Leu Asp Ser Val ggt tcg gat gat gca Gly Ser Asp Asp Ala gca ccg gaa ggc aag Ala Pro Giu Gly Lys aac cag atg ctt gat Asn Gin Met Leu Asp 115 163 211 259 307 355 403 WO 01/00804 WO 0100804PCT/IBOO/00922 gag gtt Giu Val Cct gtg Pro Val gag gct Giu Ala 135 att agt Ile Ser 150 ttt gat Phe Asp gtc acc Val Thr tac aac Tyr Asn tct gag Ser Giu 215 cgg gcg Arg Ala 105 ttg gct Leu Ala 120 cag ggt Gin Gly cca. ctg Pro Leu gca. gat Ala Asp aat att Asn Ile 185 ggc aac Gly Asn 200 ctc atc Leu Ile act Thr g cq Ala gta Val1 agt Se r tct Ser 170 ctt Leu gtg Vai Gi y ggt gtg Gly Val cag ggt Gin Gly cct gcg Pro Ala 140 gca gat Ala Asp 155 gcc atg Ala Met gat gaa Asp Giu ttt ggC Phe Gly ctg ctg Leu Leu 220 ctg Leu gtg Val 125 gag Glu gag Giugat Asp tac Tyr gca Aila 205 gtg ValI gat gct Asp Ala gct cag Ala Gin atc gcc Ile Ala acc ggc Thr Gly 160 tcc gca.
Ser Ala 175 gac ggc Asp Giy gca, acc Ala Thr gcg gtc Ala Val gat Asp atg Met gca Ala 145 atc Ile gag Giu gat Asp agc Ser gtt Val 225 gt t Va 1 115 cca Pro att Ile tcg S er cgt Arg act Thr 195 ga c Asp atc Ile ttC ggt tcg ttc atc gct gcc ggt atg ccg ctg atc tct Phe Gly Ser Phe Ilie Ala Ala Gly Met Pro Leu Ile Ser 230 235 240 <210> 216 <211> 242 <212> PRT <213> Corynebacteriun giutamicum <400> 216 Val Ala Lys Phe Leu Tyr Lys Leu Gly Ser Thr Ala Tyr Gin Lys Lys 1 5 10 Trp Pro Phe Leu Ala Vai Trp Leu Val Ile Leu Ile Gly Ile Thr Thr 25 Leu Ala Gly Leu Tyr Ala Lys Pro Thr Ser Ser Ser Phe Ser Ile Pro 40 Gly Leu Asp Ser Val Thr Thr Met Giu Lys Met Gin Giu Arg Phe Pro 55 WO 01/00804 WO 0100804PCT/IBOO/00922 Gly Ala Asn Asp Met Ala 145 Ilie Giu Asp Se r Ser Asp Asp Ala Thr Ser Ala Pro Thr Gly Ser Val Val Ile Gin Pro Gin Ser Thr 130 Asp Ile Asp Leu Leu 210 Glu Met Val1 115 Pro Ile S er Arg Thr 195 Asp Gly Lys Leu Asp 100 Val Asp Aia Leu Glu Ser Met Thr 165 Glu Lys 180 Val Val Met Thr Thr Leu Glu Val Pro Val Glu Ala 135 Ile Ser 150 Phe Asp Val Thr Tyr Asn Ser Giu 215 Asp Pro 90 Ala Thr 105 Ala Ala Gly Val Leu Ser Asp Ser 170 Ile Leu 185 Asn Val Ile Gly Val1 Val1 Gly Ala 140 Asp Met Glu Gi y Leu 220 Gly Leu Val 125 Glu Glu Asp Tyr Al a 205 Val1 Glu Asp Ala Ile Thr Se r 175 Asp Al a Ala Val Leu Ile Val Thr Phe Gly Ser Phe Ile Ala Ala Giy Met Pro Leu 225 230 235 240 Ile Ser <210> 217 <211> 2313 <212> DNA <213> Corynebacterium glutarnicum <220> <221> CDS <222> (2290) <223> RXA00479 <400> 217 tagatcccaa ggctcaaaat ttattactta aacaagttga gcaactagcc agccgcaaat cttagaacta acctttacgc ctttaacgga agtgaatttg atg tct act agc atc 115 Met Ser Thr Ser Ile 1 aca aca gag aac aag aag aaa tct ggt cct cct cgc ttg atg aga atc 163 Thr Thr Glu Asn Lys Lys Lys Ser Gly Pro Pro Arg Leu Met Arg Ile 15 WO 01/00804 WO 0100804PCT/1B00/00922 ttt otg ccc ttg cta att tta Leu Leu Ile Leu gtt tgg ott gta gga Val Trp Leu Val Gly Phe 9gc Gly ace Thr ttg Leu gtC ValI gt t Val Oct Pro ctc Leu acc Thr 150 ceg Pro ggg Gi y at c Ile ttg Leu Leu ggt Gly aca Thr gga Gly agc Ser gtt Val got Al a aat Asn 135 ttg Leu get Al a eta Leu gte Val ttt Phe 215 Pro Oct Pro tat Tyr gat Asp gat Asp got Al a att Ile 120 cca Pro ace Thr ggg Gly etc Leu tat Tyr 200 gcg Al a got gga gtc Ala Gly Val 30 tat Tyr ctg Leu ttt Phe ga a Giu ggg Gly 105 cca Pro tca Ser cag Gin ttt Phe eta Leu 185 ego Arg etg Leu ttt Phe cca Pro act Th r ccc Pro ott Leu too Ser gog Ala caa Gin ac Thr 170 gca Ala t cc Ser act Thr ggc Gi y gaa Giu gat Asp 75 tta Leu tea Ser gag Gi u gag Gi u acg Thr 155 got Al a gte Val ttc Phe gt a Val1 aag Lys tot Ser 60 tot Ser aca Thr ga a Giu gac Asp ct g Leu 140 cog Pro gat Asp gee Al a att Ile got Al a 220 gt t Val1 gee Ala gaa Giu cag Gin tta Leu ggc Gly 125 acg Thr gao Asp etc Leu ttg Leu ct g Leu 205 eta Leu agt Ser gat Asp too Se r eaa Gin gao Asp 110 aga Arg gaa Giu tat Tyr age Ser get Al a 190 ccc Pro ttg Leu gag Glu gee Ala ate Ile gac Asp 95 ata Ile got Ala ago Ser gtg Val gca Ala 175 gc Al a ate Ile gtg Val1 gte Val1 act Thr oca Pro 80 a to Ile gtt Val1 gte Val gte Val1 ago Ser 160 got Al a gt 0 ValI gcc Ala gtg Val1 tee Ser caa Gin gee Al a aca Th r too Se r caa Gin gag Giu 145 a 00 Thr ttc Phe ott Leu gtg Val1 tg Trp 225 aac Asn cag Gln gte Val etc Leu gaa Giu 115 tt t Phe etc Leu Val1 ggt Gi y att Ile 195 gc Ala eta Leu age eag Ser Gin gaa eag Glu Gln gta atg Val Met aat gaa Asn Glu 100 gte tee Val Ser gte ccc Val Pro tot gag Ser Giu ace gga Thr Gly 165 att gat Ile Asp 180 ott gte Leu Val aco agt Thr Ser got aag Ala Lys 259 307 355 403 451 499 547 595 643 691 739 787 tgg gao ate ctg otg ott tog Trp Asp Ile Leu Leu Leu Ser 230 235 cag act caa ggc ate etc ttc att Gin Thr Gin Gly Ile Leu Phe Ile WO 01/00804 WO 0106804PCTIBOOIOO922 ctg gtc att ggc gCC gcc acc gac tac tea ttg eta tac gtt gct egt Leu Val Ile Gly Ala Ala Thr Asp Tyr Ser Leu Leu Tyr Val Ala Arg ttc Phe aaa Lys gtt Val tee Ser 310 tet Ser gee Ala aaa Lys gt g Val etc Leu 390 caa Gin get Ala ate Ile egt Arc gcc Ala att Ile 295 a eq Thr get Ala ttt Phe aae Asn gag Gi u 375 ttg Le u t e Ser tta Leu Itt lai gaa Giu ate I le 280 *gcg Ala eta *Leu et t Leu t gg Trp gac Asp 360 cag Gin ggt Gly gae Asp gge Gly gat Asp gag Giu 265 egg Arg gge Gly ggt Gly act Thr cc Pro 345 ate Ilie eat His geg Ala eta Leu gaa Giu 425 gaa E Giu I ttz Let gca Al a etc Leu e ea Pro etg Leu 330 88 g Lys ccc Pro cet Pro get Ala gt t Vali 410 :8 e Us5 ca ege Arg teg Ser ett Leu gta Val 315 eta Leu cga Arg gee Ala cgt Arg ttc Phe 395 etg Leu tte Phe cag qj 260 gtt ValI gtg ValI tgt Cys 300 get Ala eca Pro cca Pro age Se r gea Ala 380 gt t Vl ggt ily cce ?ro cea ca~ Gir gaz Gi 285 t tc Leu t eg Ser gee Ala 888 Lys ggg Gi y 365 ate Ile Ccc Pro tee Se r ggt Gly gca icaa i Gin 270 cee Pro eta Leu gtg *Val etg Leu tae Tyr 350 ate Ile t gg Trp aca Thr tct Ser gga I Gly 1 430 eagC Gin P gat Asp att Ile ttt Phe gqe Gi y ctg Leu 335 gaa Giu t gg Trp gt a Val ct a Leu gaa 3iu 415 cce ~er jet ~la aa Ly~ eta Let agt Sex att Ile 320C ttt Phe eet Pro tea Ser t Ct Ser aaa Lys 400 gea Ala ggc Gly gct Al a ggg9 3 Giy :gee jAia gat Asp 305 att Ile gta Vai gaa Giu aaa Lys a ca Thr 385 geg Ala egt Arg agt Ser gao Asp 4 get g Ala A 465 atz IlE t Cs Sez 2 ttc Leu ttt Phe ttC Phe aaa Lys gt g Val 370 ctt Leu gac ga t Nsp :ct Pro t a Ia 1 aec
LSP
gce Ala 275 9ge Giy aaa Lys gea Ala ggt Gly gee Ala 355 get Ala att Ile ggt Giy gge Gly get Ala 435 gte Val1 tee Ser ci Thi agc Sex t ct Ser a tg Met egg Arg 340 egt Arg ga t Asp gt g Vali gtg Val cag Gin, 420 tat Tyr ctt Leu cee Pro ggg Gly act Thr aac Asn Ictt Leu 325 gtg Val geg Ala tta Leu Ct t Leu toe Ser 405 cag Gin att Ile aac As n tct Ser 883 931 979 1027 1075 1123 1171 1219 1267 1315 1363 1411 1459 1507 1555 *hr Gin Aia Ala 440 aac gao aat ttc gag act gta act gta act agt Asn Asp Asn Phe Glu Thr Val Thr Val Thr Ser 455 460 ggc tea gcc eca ate ace gct gac ggt att gtg ceg tta ggt tet ggt WO 01/00804 WO 01/080-fPCT/IBOO/00922 Gly Ser 470 aca gct Thr Ala aca ctt Thr Leu agt atc Ser Ile ggt gte Gly Val 535 cgc aac Arg Asn 550 atg ctg Met Leu acc gtg Thr Val aat cac Asn His gga ttt Gly Phe 615 gtc acc Val Thr 630 att ctt Ile Leu gta gtt Val Val tC ctg Phe Leu 475 480 Ala Pro Ile Thr Ala Asp Gly Ile Val Pro Leu Gly Ser c ca Pro gte Val ego Arg 520 act Th r ctg Leu t tg Leu gtg Val1 gtt Val1 600 gta Val1 cga Arg ega Arg ctc Leu gca Ala 680 ggc Gly gaa Gi u 505 eaa Gin gea Ala ate Ilie etg Leu tot Se r 585 ttC Phe ttt Phe ate Ile gge Gly gc Ala 665 caa a Gin I ceg Pro 490 gca Ala act Th~r act Thr ate: Ile Arg 570 ttt Phe agt Ser t ta Leu cgt Arg ct g Leu 650 Ica kla itt l~e gta.
Vai cca Pro ttt Phe tee Ser cca Pro 555 tct Ser get Ala ttC Phe gta Val1 gaa Giu 635 aca Thr acg Thr gee AlaI gtt Val gat Asp gca Ala gta Vali 540 at t Ile att Ile act Thr eca Pro gee Ala 620 gaa Giu gta Val tte Phe tC Phe gta Val tee Sei ga t Asp 525 gac Asp gta Val1 gte Val1 get Aia gga Giy 605 ttg Leu acc Th r ace Thr gea Ala at t Ile 685 gaa Glu ga a Gi u 510 gaa Glu act Thr t tg Leu gca Ala tta Leu 590 gca Al a gge Gly aaa Lys gge Gly gea Aila 670 gte Val ggg Giy 495 gaa Glu aat Asn aac As n ctg Leu cca Pro 575 gge Gi y gac Asp ate Ile ace Thr gga Gi y 655 etc Leu get Ala caa Gin get Ala at a Ile gat Asp gte Val1 560 etc Leu gtg Val1 ec Pro gac Asp ca c His 640 gta ValI tat Tyr ttt Phe gte Vali ca a Gin tea Ser gee Ala 545 att Ile Ctg Leu get Al a gea Al a tac Tyr 625 gge Gly a tt Ile gte Val1 gga Gly ct t Leu aaa Lys geg Ala 530 tee Se r tt g Leu eta.
Leu get Ala gta Val 610 aae Asn aea Thr ace Th r ate Ile gtt Val 690 tta Leu get Ala 515 gta Val ate Ile gt t Val1 gta Val1 t ta Leu 595 ct Pro att Ile aga Arg tea.
Se r cca Pro 675 ott Leu caa Gin 500 at t I le gt a Val1 cat His att Ile gte Val1 580 ct t Leu etc Leu ttC Phe ctt Leu get Ala 660 at t Ile att Ile Gi y 485 gca Ala ege Arg gge Gly gac Asp etc Leu 565 ace Th r t te Phe t ac Tyr tta Leu gga Gly 645 gga Gi y eta Leu ga t Asp 1603 1651 1699 1747 1795 1843 1891 1939 1987 2035 2083 2131 2179 2227 ace ctg etc Thr Leu Leu gt t Val1 ege gee ttc ttg gtg ect gct ttg ttc tac gac ate Arg Ala Phe Leu Val Pro Ala Leu Phe Tyr Asp Ile WO 01/00804 695 gga ccg aaa atc Gly Pro Lys Ile 710 aag cag cct cag Lys Gin Pro Gin PCT/IBOO/00922 700 705 tgg tgg ccg tca aaa ttg icc aat cag aaa tac cag Trp Trp Pro Ser Lys Leu Ser Asn Gin Lys Tyr Gin 715 720 725 cta tgacacacca aaattcgcct ctc Leu 730 2275 2313 <210> 218 <211> 730 <212> PRT <213> Corynebacterium giutamicum <400> 218 Met Ser Thr Ser Ilie Thr Thr Giu Asn 1 Arg Leu Met Vai Gly Ala Ser Ser Asr Gin Vai Gin Ala Ile Val Thr Gin Leu Ser Asp Giu 115 Gin Val Phe 130 Glu Lys Leu 145 Thr Tyr Val Phe Ala Giy Leu Val Ile 195 Arg Gi y Ser Giu Val1 As n 100 Val1 ValI Ser Thr Ile 180 Leu 5 Ile Val Gin Gin Met Glu Ser Pro Glu Gly 165 Asp Val Phe Gly Thr Leu 70 Val1 Val Pro Leu Th r 150 Pro 3i y Leu Gly Th r 55 Gi y Ser Val Ala Asn 135 Leu Ala Leu Pro Pro Tyr Asp Asp Ala Ile 120 Pro Thr Gly Leu Al a 25 Tyr Leu Phe Giu GI y 105 Pro Ser Gin Phe Leu 185 Lys 10 Leu Phe Pro Thr Pro 90 Leu Ser Al a Gin Thr 170 Ala Leu Gi y Glu Asp 75 Leu S er Glu Giu Th r 155 A~la Val1 Ile Lys Ser Ser Thr Giu Asp Leu 140 Pro Asp Al a Leu ValI Ala Glu Gin Leu Gly 125 Thr Asp Leu Leu Leu Lys Lys Ser Gly Pro Pro Val1 Ser Asp Ser Gin Asp 110 Arg Giu Tyr Ser Ala 190 Pro Trp Glu Ala Ile Asp Ile Ala Ser Val1 Al a 175 Ala Ile Leu Val1 Th r Pro Ile Val Val Val1 Se r 160 Ala Val Al a Ile Val Tyr 200 Arg Ser Phe Ile 205 Val Leu Ala Thr Ser Leu Phe Ala Leu Thr Val Ala Leu Leu Val Val WO 01/00804 WO 0100804PCT/IBOO/00922 Trp 225 Gly Le u Gi y Ala Asp 305 Ile Val1 Giu Lys Thr 385 Ala Arg Ser Asp1 Ala 465 Pro Trp Ile Tyr Ilie Ser 290 Leu Phe Phe Lys ValI 370 Leu Asp Asp Pro Vfal1 450 ksp ,eu Lei Lei Va.
Ali 271 Gl) Lys Al a Gi y Ala 355 Ala Ile Gly Gi y Al a 435 Val Ser Gly u Ala u~ Phe L Ala 260 Thr /Ser Ser Met Arg 340 Arg Asp Val Val Gln 420 Tyr Leu Pro Ser C Lys Ile 245 Arg Gi y Th r Asn Leu 325 Val Ala Leu Leu Ser 405 Gin Ilie ks n ;er ;i 85 Trp Asp 230 Leu Val Phe Arg Lys Ala Val Ile 295 Ser Thr 310 Ser Ala Ala Phe Lys Asn Vai Giu 375 Leu Leu 390 Gin Ser Ala Leu Ile Val Asn Asp 455 Gly Ser 470 Thr Ala Thr Leu Gl IlE 28C Al a Leu Leu Trp Asp 360 Gin GI y Asp Gly Asp 440 As n Al a Pro fl eLeu SGly i Glu 265 Arg Gly aGly Thr Pro 345 Ilie His Al a Leu Giu 425 Glu Phe Pro Gly Giu Let Ala 250 Leu Ala Leu Pro Leu 330 Lys Pro Pro Ala Val 410 His rhr 31 u Ile Pro 190 l a aLeu 235 aAla aArg Ser Leu Val1 315 Leu Arg Al a Arg Phe 395 Leu Phe Gin Thr Thr 475 Val Ser Thr ValI Val1 Cys 300 Al a Pro Pro Ser Ala 380 Val Gly Pro Ala Val 460 kla lal Gly Asp Gin Glu 285 Leu Ser Ala Lys Gly 365 Ile Pro Ser Gly Ala 445 Thr Asp Val Gin Tyr Gin 270 Pro Leu Val1 Leu Tyr 350 Ile Trp Thr Ser Gi y 430 Gin Val1 Gly 3lu Thr Ser 255 Asp Ile Phe Gly Leu 335 Glu Trp Val Leu Giu 415 Ser Ala Thr Ile Gly 495 Gin 240 Leu Lys Leu Ser Ile 320 Phe Pro Ser S er Lys 400 Ala Gi y Ala Ser Val1 480 Gin 4 Val Leu Leu Gin Ala Pro Asp Ser Giu Giu Ala 510 500 505 Gin Lys Ala Ile Arg Ser Ile Arg Gin Thr Phe Ala Asp Glu Asn Ile WO 01/00804 WO 0100804PCT/IBOO/00922 Ser Ala 545 Ile Leu Al a Al a Ty r 625 Gly Ile Val Gly Leu 705 Ala Val 530 Ser Ile Leu Val Leu Val Ala Leu 595 Val Pro 610 Asn Ile Thr Arg Thr Ser Ile Pro 675 Val Leu 690 Phe Tyr Val Gly Gly Val 535 His Asp Arg Asn 550 Ile Leu Met Leu 565 Val Thr Thr Val 580 Leu Phe Asn His Leu Tyr Gly Phe 615 Phe Leu Val Thr 630 Leu Gly Ile Leu 645 Ala Gly Val Val 660 Ile Leu Phe Leu Ile Asp Thr Leu 695 Asp Ile Gly Pro 710 Thr Leu Leu Val1 Val1 600 Val1 Arg Arg Leu Ala 680 Leu Lys Ala Ile Leu Ser 585 Phe Phe Ile Gi y Ala 665 Gln Val Ile Thr I le Arg 570 Phe Ser Leu Arg Leu 650 Ala Ile Arg Trp Ser Pro 555 Ser Al a Phe Val1 Giu 635 Thr Thr Ala Ala Trp 715 Val1 540 Ile Ile Tb r Pro Ala 620 Glu Val Phe Phe Phe 700 Asp Val Val Ala Gi y 605 Leu Thr Thr Ala Ile 685 Leu Asn Leu Pro 575 Gly Asp Ile Thr Gly 655 Leu Al a Pro Asp Val1 560 Leu ValI Pro Asp His 640 Val1 Tyr Phe Al a Se r 720 Pro Ser Lys Leu Asn Gin Lys Tyr Gin 725 Lys Gin Pro Gin c210> 219 <211> 983 <212> DNA <213> Corynebacterium glutanicum <220> <221> CDS <222> (960) <223> RXN03124 <400> 219 atg act cct acc ctg gcg tcg atg att ggt ctg gct gtc ggt atc gac 48 Met Thr Pro Thr Leu Ala Ser Met Ile Gly Leu Ala Val Gly Ile Asp 1 5 10 WO 01/00804 WO 0100804PCT/IBOO/00922 tao gcg Tyr Ala cta ttt atc Leu Phe Ile gtg tcc ogt ttc cgc aat gag ttg att tct cag Val Ser Arg Phe Arg Asn Gin Leu Ie Ser Gin act Thr acc Thr act Thr ctg Leu at Ile ttc Phe cgc Arg atg Met 145 ctg Len aat Asn gcg Ala cgo Arg gaa 9gC Gly atg Met gcg Ala gt Val got Al a cto Leu gig Val1 130 ggt Gi y ctg Leu atg Met ccg Pro aac Asn .Z 210 gaa c got Ala cg Pro ggi Gly gct Al a gc Ala cca Pro 115 cot Pro ct g Leu gtt Val1 :go D~rg cgc krg 195 ;cg l~a ~gc aal Asi ttC Let tct S ex ctg Leu gca Ala 100 gct Ala gg a Gly aag Lys ggc Gly ctg Len 180 acg Thr ccc Pro cca t ga -i Asj jAl.
Al~ toc Se2 *atc Ile ctg Leu cct Pro t gg Trp gtc Val 165 gcc Al a 9g9 Gly atg Met ttg t cti p Le' t gol a Al a Va: a tc Ilc acc Thr ctt Leu a ag Lys gt c Val1 150 gt t Val1 atg Met tat Tyr att.
Ile gt g ValI 230 g gag cca u Glu Pro 40 t cgt gcg a Arg Ala 55 gta t LVal Phe -att aat Ile Asn -gtt gc *Val Ala *ggc ctg IGly Len 120 git cog Val Pro 135 ogo Ott Arg Len ttg ott Leu Len cog act Pro Thr gac aig Asp Met 200 gcg ott z Ala Leu I 215 ttt gga c Phe Gly G aag Lys oat His gog Ala at Ile etc Ile 105 ott Len gati Asp gig Val1 ggt Gly gat Asp 185 acg Chr Ito 1le :ag I n gaa Gin *gcg Ala *ggt Gly cca Pro gca Ala ggc Gly cct Pro ogo Arg gca Ala 170 ggC Gly gca Ala gaoc Asp gcg t; Ala V~ tg Leu at g Met acc Thr 75 ttt Phe gtt Val1 act Thr gag Gin eag Lys 155 atc Ile 300 Thr gat %sp ;ca l.a ~tg al1 got Al a gga Gly 60 a og Thr cta Len ctg Leu ogo Arg ga c Asp 140 aig Met gca Ala too Ser gog Ala aco Thr 220 gag Glu gag Gin 45 atg Met Igig Val aoo Thr gt t Val1 ato Ile 125 gag Gin cog Pro at Ile eog Th r tic Phe 205 gao Asp caea Gin cg t Arg got Al a ct g Leu gtg Val1 got Ala 110 to Phe ag Lys gtg Val ct Pro ot g Len 190 99c :Giy gtc Val to Phe cig Leu gt g Val1 atc Ile atg Met ctg Len gca Ala cca Pro got Al a gog Ala 175 ggo Gly cog Pro oct Pro t ig Len ogo Arg ggc Gl y got Ala gcc Aia too Ser gca Ala ecg Thr tao Tyr 160 acc Thr aco Thr ggc Gly gag Gin aac Asn 240 96 144 192 240 288 336 384 432 480 528 576 624 672 720 Gin Gin Arg Pro Len 225 act get ggt gig aeg eat got ceg etc act ceg aco acg gag eat ttO WO 01/00804 Thr Asp Gly Val Lys Asn Ala Gin Ile 245 gat acc gcg cag atc ctg tta ccc cag Asp Thr Ala Gin Ile Leu Leu Pro Gin 260 265 gca cct ctg aga. ctc tcg caa ctc ttc Ala Pro Leu Arg Leu Ser Gin Leu Phe 275 280 ctg atg aca ccg gcg cga cgt atg gca Leu Met Thr Pro Ala Arg Arg Met Ala 290 295 acg atg aca tct ctq ctc gcc tcg gcg Thr Met Thr Ser Leu Leu Ala Ser Ala 305 310 tgatcgtttt ggttctagcg ttc <210> 220 <211> 320 <212> PRT <213> Corynebacterium giutamicui <400> 220 Met Thr Pro Thr Leu Ala Ser Met Ile 1 1 5 Tyr Ala Leu Phe Ile Val Ser Arg Phe 25 Thr Gly Ala Asn Asp Leu Giu Pro Lys 40 Thr Met Pro Leu Ala Ala Aug Ala His Thr Ala Gly Ser Ala Val Val Phe Ala 70 Leu Val Ala Leu Ser Ile Ile As Ile Ile Ala Ala Ala Ilie Thr Val Ala Ile 100 105 Phe Leu Pro Ala Leu Leu Gly Leu Leu 115 120 Arq Val Pro Gly Pro Lys Val Pro Asp 130 135 Met Gly Leu Lys Trp Val Arg Leu Val 145 150 PCTIBOO/00922 Gin ttg Leu ca g Gin ct g Leu tcc Ser 315 Gly 10 Arg Gi u Al a Gly Pro 90 Alia
G
1 y Pro krg Leu Asn Leu Met Th r 75 Phe ValI Thr Giu Lys 155 Val1 Leu Glu Met Val Thr Val1 Ile 125 Glu Pro Gly Ile Arg Ala Leu Val Al a 110 Phe Lys Val Ile Se r Leu Val1 Ile Met Leu Ala Pro Ala Asp Gin Arg Gi y Ala Ala Ser Ala Thr Tyr 160 Leu Asn Ala Arg Glu 225 Thr Asp Al a Leu Thr 305 WO 01/00804 Leu Val Gly Met Arg Leu 180 Pro Arg Thr 195 Asn Ala Pro 210 Glu Arg Pro Asp Gly Val Thr Ala Gln 260 Pro Leu Arg 275 Met Thr Pro 290 Met Thr Ser ValI 165 Ala Gly Met Leu Lys 245 I le Leu Aila Leu Val Met Tyr I le Val1 230 Asn Leu Ser Arg Leu 310 Leu Pro Asp Ala 215 Phe Ala Leu Gln Arg 295 Ala Leu Gly Thr Asp 185 Met Thr 200 Leu Ile Gly Gln Gln Ile Pro Gln 265 Leu Phe 280 Met Ala Ser Ala Ala Ile 170 Gly Thr Ala Asp Asp Ala Ala Val 235 Thr Gln 250 Asn Leu Val Gln Leu Leu Thr Ser 315 I le Thr Phe 205 Asp Gln Th r Arg Leu 285 Ser Phe Pro Leu 190 Gl y Val1 Phe Glu Ser 270 Arg Pro Leu Ala Thr 175 Gly Thr Pro Gly Pro Glu Leu Asn 240 Asn Phe 255 Met Ser Pro Ser Gln Phe Thr Phe 320 PCT/IBOO/00922 <210> 221 <211> 762 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> <223> FRXA01180 <400> 221 atg act cct acc ctg gcg tcg atg att ggt ctg gct gtc qgt atc gac Met Thr Pro Thr Leu Ala Ser Met Ile Gly tLeu Ala Val Gly Ile Asp 1 5 10 tac gcg cta ttt atc gtg tcc cgt ttc cgc aat gag ttg att tct cag Tyr Ala Leu Phe Ile Val Ser Arg Phe Arg Asn Glu Leu Ile Ser Gln 25 act ggc gct aat gat ctg gag cca aag gaa ttg gct gag cgt ctg cgc Thr Gly Ala Asri Asp Leu Glu Pro Lys Glu Leu Ala Glu Arg Leu Arg 40 WO 01/00804 WO 0100804PCT/IBOO/00922 acc atg ccg ttq gc~t gct cgt gq cat gcg atg gga atg gct gtg ggc Gly Met Ala Val Gly Thr act Thr ctg Leu att Ile tic Phe cgc Arg aig Met 145 ci g Le u eat Asn gcg Ala cgc Arg.
gaa Gin 225 Met gcg Ala gt Val gct Ala ci c Leu gig Val1 130 ggt Gi y ci g Leu atg Met ccg Pro aac PAsn 210 gaa Glu Pro qgt Gly gct Ala gcc Al a cc a Pro 115 cci Pro ctg Leu gt Val cgc Arg cgc Arg 195 gcg Ala cgc Arg Leu Ala Ala Arg tct gcq gtt gia Ser Ala Val Val 70 ctg icg atc att Leu Ser Ile Ile gca aic acc gt Ala Ile Thr Val 100 gci ctg cit ggc Ala Len Leu Gly gga cci eag gt Gly Pro Lys Val 135 aeg tgg gtc cgc Lys Trp Val Arg 150 ggc gic git tig Gly Val Val Leu 165 ctg gcc atg ccg Leu Ala Met Pro 180 acg ggg tat gac Thr Gly Tyr Asp ccc aig att gcg Pro Met Ile Ala 215 cca itg gtg ttt Pro Leu Val Phe 230 Ala His Ala Met tc Phe aat As n gcc Ala ci g Leu 120 ccg Pro ctt Leu ctt Len act Thr atg Met 200 cti Leu gga Gly gcg Ala at Ile atc Ile 105 cii Leu gat Asp gig Val1 ggi GI y gati Asp 185 acg Thr atc Ile cag Gin ggt Gly cc a Pro 90 gca Ala ggc Gly cci Pro cqc Arg gca Ala 170 ggc Gly gca Al1a gac Asp gcg Al a acc Thr 75 ttt Phe gt Val act Thr gag Glu aag Lys 155 aic Ile acc Thr gat Asp gca Ala gtg Val 235 acg Thr cta Leu ctg Leu cgc Arg gac Asp 140 a ig Met gca Ala icc Ser gcg Al a acc Thr 220 gag Glu gt g Val1 acc Th r gt Val etc Ile 125 gag Glu ccg Pro ati Ile acg Thr ttc Phe 205 gac Asp caa Gin cig Len gig Val1 gct Ala 110 tic Phe ag Lys gt g ValI cci Pro cig Leu 190 ggc Gly gi c Val1 tc Phe atc Ile aig Met ctg Leu gca Ala cca Pro gci Ala gcg Ala 175 9gc Gly ccg Pro cci Pro ttg Len g ci Aila gcc Al a tcc Se r gca Ala acg Thr tac Tyr 160 acc Thr acc Thr ggc Gi y gag Glu aac Asn 240 192 240 2B8 336 384 432 480 528 576 624 672 720 act gat ggi gig Thr Asp Gly Val aag Lys 245 aet gci cag aic Asn Ala Gin Ilie act cag acc acg gag Thr Gin Thr Thr Gin <210> 222 <211> 254 <212> PRT WO 01/00804 PCT/IBOO/00922 <213> Corynebacterium giutamicum <400> 222 Met Thr Pro Thr Leu Ala Ser Met Ile Gly Leu Ala Val Gly Ile Asp 1 5 10 Tyr Ala Leu Phe Ile Val Ser Arg Ph6 Arg Asn Glu Leu Ile Ser Gin 25 Thr Giy Ala Asn Asp Leu Giu Pro Lys Glu Leu Ala Glu Arg Leu Arg 40 Thr Met Pro Leu Ala Ala Arg Ala His Ala Met Gly Met Ala Val Gly 55 Thr Ala Gly Ser Ala Val Val Phe Ala Gly Thr Thr Val Leu Ile Ala 70 75 Leu Val Ala Leu Ser Ilie Ile Asn Ile Pro Phe Leu Thr Val Met Ala 90 Ilie Ala Ala Ala Ile Thr Val Ala Ile Ala Val Leu Val Ala Leu Ser 100 105 110 Phe Leu Pro Ala Leu Leu Gly Leu Leu Giy Thr Arg Ile Phe Ala Ala 115 120 125 Arg Val Pro Giy Pro Lys Val Pro Asp Pro Glu Asp Giu Lys Pro Thr 130 135 140 Met Gly Leu Lys Trp Val Arg Leu Val Arg Lys Met Pro Val Ala Tyr 145 150 155 160 Leu Leu Val Gly Val Val Leu Leu Gly Ala Ile Ala Ile Pro Ala Thr 165 170 175 Asn Met Arg Leu Ala Met Pro Thr Asp Gly Thr Ser Thr Leu Gly Thr 180 185 190 Ala Pro Arg Thr Gly Tyr Asp Met Thr Ala Asp Ala Phe Gly Pro Gly 195 200 205 Arg Asn Ala Pro Met Ile Ala Leu Ilie Asp Ala Thr Asp Val Pro Giu 210 215 220 Glu Glu Arg Pro Leu Val Phe Gly Gin Ala Val Glu Gin Phe Leu Asn 225 230 235 240 Thr Asp Gly Val Lys Asn Ala Gin Ile Thr Gin Thr Thr Giu 245 250 <210> 223 <211> 393 <212> DNA <213> Corynebacterium giutamicum WO 01/00804 <220> <221> CDS <222> (370) <223> RXA02586 <400> 223 PCT/IBOO/00922 ttctctgaga tcgtcatg gatgccacca tcatccgc gac Asp a tg Met ege Arg ggC Gly gat Asp ct t Leu t gg T rp g gc Gly gac Asp gtg Val1 tcc Se r ct a Leu at gaagtacatc gcgttcggca tgatcgcagc gctgattctg at gctgcttgtc ccccgccgtg atg cac ctg ctt ege Met His Leu Leu Arg 1 gca ccc ggc ttc gtt aaa aag gee tac acc gte Ala Pro Gly Phe Val Lys Lys Ala Tyr Thr Val gag gtg gag gaa gca cct cgc cca acc acc cgt Glu Val Gin Gin Ala Pro Arg Pro Thr Thr Arg 30 gag gaa gte aec gtg cat gaa gca gtt gte get Gin Glu Val Thr Val His Glu Ala Val Val Ala tct cgc ggt ggt ttg agc acg cag gaa aac cgt Ser Arg Gly Gly Len Ser Thr Gln Giu Asn Arg gtg gaa ctt aag get cgt ttg gaa aag cgc agg Val Glu Leu Lys Ala Arg Leu Gin Lys Arg Arg 75 80 taaatctatg cgaggatttt tea <210> 224 <211> <212> PRT <213> Corynebacteriui glutamicun <400> 224 Met His Leu Leu Arg Asp Asp Asn 1 5 Lys Ala Tyr Thr Val Met Gly His Arg Pro Thr Thr Arg Arg Len Asn 40 Gin Ala Val Val Ala Gly Asp Thr 55 Thr Gin Glu Asn Arg Asp Len Val 70 Trp Trp Ala Pro Gly Phe Val Lys 10 Gly Ser Glu Val Gin Gin Ala Pro 25 Asp Asp Giu Glu Val Thr Val His Val Ala Ser Arg Gly Gly Leu Ser Ser Phe Val Gin Len Lys Ala Arg 75 WO 01/00804 PCT/IBOO/00922 Leu Glu Lys Arg Arg Leu Glu Asp Leu Asp <210> 225 <211> 2214 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> (101)..(2191) <223> RXA02587 <400> 225 agcctggata acctgccaga cggtggcgca tggctgcagc ttgttatcca accgccacaa ttcccaggag taatccaccc cgttccgccc tctgactgcc gt g ttt tct aaa tgg ggc cac Gly His gcc gcg Ala Ala cgc atg Arg Met gcg gcg Ala Ala gtc gtg Val Val gag gtg Glu Val aac cct Asn Pro caa aat Gin Asn gct Al a ttg Leu cag Gin atc Ile ct g Leu tcc Se r gaa Giu 105 ctc Leu tac aga Tyr Arg gct ttg Ala Leu gaa gga Glu Gly gag ttg Glu Leu ttt act Phe Thr 75 agc atc Ser Ile gtc agc Val Ser agc aaa Ser Lys ttt Phe ttt Phe tgg Trp gag Giu 60 gcg Ala t ct Ser cac His ga c Asp agg Arg gt c Val1 gat Asp acc Thr cct Pro ggc Gly at c Ile ggc Gly 125 cgc Arg att Ile 30 gat Asp ttt Phe ga a Gi u tac Tyr aac Asn 110 acc Thr gt t Val1 Gi y ggt Gly cgt Arg act Thr 80 gat Asp tac Tyr acc Thr Val1 1 ccg Pro acc Thr t ct Ser gac Asp t ct Ser ggg Gi y ttt Phe ttt Phe tta Leu aag Lys t cc Ser aat Asn ttc Phe ct a Leu gac Asp g ca Ala 130 Phe Sex Lys gt c Val et g Leu t cg Se r ga c Asp gat Asp atc Ile act Thr 115 g ct Ala gtc Val1 ggc Gi y acc Thr ggc Gly gat Asp gag Giu 100 cgt Arg ctc Leu Trp atc Ile ga c Asp gct Ala gat Asp gca Al a aac Asn aat Asn ggg Gly 115 163 211 259 307 355 403 451 499 547 ctc aaa ggt qac ggc gag caa acg ctg aag gac ttc cgg gag ait gaa Glu Ile Glu Leu Lys 135 Giy Asp Giy Giu Gin Thr Leu Lys Asp Phe Arg wo 01/00804 WO 0100804PCTIBOOIOO922 ga t Asp 150 gcg Al a ga t Asp ctg Len gtg Val1 gct Ala 230 ctg Len t tc Phe a cc Thr gt g Val1 aag Lys 310 at g Met atc Ile cag ctc cat ccg gac aac ctt gcc Gln ggt Gly at t I le ctc Leu 9gC Gly 215 gga Gly ggc Gly cgt Arg act Thr gct Ala 295 tcg Ser t cg Ser gat Asp Len gcc Ala t ca Ser atc I le 200 att I le ttc Phe ttg Leu gag Glu acg Thr 280 gt g Val gtg Val1 gtg Val1 aag Lys His Pro Asp 155 acc gct gta Thr Ala Val 170 cgc gcc gaa Arg Ala Gin 185 gtg ttt ggc Val Phe Gly ttg tcc atc Leu Ser Ile ttc cag gtc Phe Gln Val 235 ggt Ctt gcc Gly Leu Ala 250 gaa atg gat Gin Met Asp 265 qcg acc gcg Ala Thr Ala gCg ctg tcc Ala Leu Ser gca ttc ggt Ala Phe Gly 315 acg gtg ttg Thr Val Leu 330 tgg agt ttg Trp Ser Len 345 Asn Leu Ala ggt ggc gic acc act gag Gly Gly Val Thr Thr Glu 160 gcc Al a gtt ValI tca Ser ttg Leu 220 aac Asn att I le aag Lys ggt Gl y ggg Gly 300 qcg Ala ccg Pro cgt Arg gac Asp ttt Phe gt t Val1 205 ggt Gly gt a Val gac Asp ggc Gly aag Lys 285 ttg Len at t Ile tcg Se r cgc Arg gca Ala gcg Al a 190 gt t ValI t eg Ser ttt Phe tat T yr acc Thr 270 act Thr ttt Phe t cc Ser ctg Leu act Th r 350 ct c Len 175 ctg Leu gcc Ala ctg Len gca Ala ggc Gly 255 ccg Pro gtg Val1 gt t Val gcg Ala ttc Phe 335 gct Al a gat Asp cc t Pro gcg Ala ggc Gly caa Gln 240 tta Len gt t Val1 gt g Val ttc Phe gtt Val 320 agc Ser cga Arg gag Glu ttc Phe gcg Ala atc Ile 225 tct Se r ttc Phe ga a Glu ttc Phe cca Pro 305 ggc Gly atg Met aca Th r 9gc Gly gtg Val1 atg Met 210 ttg Len gt t ValI atg Met cag Gin tct S er 290 cag Gin ct t Len ttg Len gcg Ala atg Met gct Ala 195 cca Pro gca Ala gtg Val gt c Val1 gct Ala 275 gca Ala gct Al a gct Al a ggt Gly cgc Ar g 355 gt c Val1 165 9gC Gly ttg Len atc Ile ttg Leu ct t Leu 245 cgt Arg gcc Ala atg Met ttg Len t tg Len 325 aat Asn ttg Len 595 643 691 739 787 835 883 931 979 1027 1075 1123 1171 1219 gaa gac Gln Asp acc att tgg tac cgc gtg ccg gca tgg gca atg cgc cat gcc Thr Ile Trp Tyr Arg Val Pro Ala Trp Ala Met Arg His Ala WO 01/00804 WO 0100804PCT/IBOO/00922 aag gca gtg acc Lys Ala Val Thr 375 ccg ttg acg ggc Pro Leu Thr Gly 390 cca gct aac gac Pro Ala Asn Asp ccc gce ttc cgc Pro Ala Phe Arg 425 aac aac cag ctg Asn Asn Gin Leu 440 ctg aca gat cgt Leu Thr Asp Arg 455 gtg ttg tct act Val Leu Ser Thr 470 gag cag ctt cgc Giu Gin Leu Arg ggt ggc act cca Gly Gly Thr Pro 505 aag ctc ctc tgg Lys Leu Leu Trp 520 atg gca ttg gta Met Ala Leu Val 535 atg aec att ctg Met Thr Ile Leu 550 tte gtc gat gge Phe Val Asp Gly ctg atg agt cea Leu Met Ser Pro 585 gtg ggc gte Val Gly Val 380 gtg aaa ttc Val Lys Phe 395 ace cgc gte Thr Arg Val 410 ace gag ceg Thr Glu Pro ate gat ate Ile Asp Ile ttc ace gca Phe Thr Ala 460 ggt att eag Giy Ile Gin 475 get att tcc Ala Ile Ser 490 gcc atg gag Ala Met Giu atg get etc Met Ala Leu ttt qgt tcg Phe Gly Ser 540 ggt atg ggt Gly Met Gly 555 gtg ggt gee Val Gly Ala 570 gtg ctg gtg Val Leu Val gta.
Val 9gc Gly gee Ala gte ValI tat Tyr 445 ggt Gly gat Asp gte Val ate Ile tae Tyr 525 gtg Val1 gee Ala age Se r et g Le u ttg etc ttg ctt get ctt aca gtg Leu Leu Leu Leu Ala Leu Thr Val 385 gge Gly ca a Gin aag Lys 430 qt t Val1 geg Ala cgt Arg cet Pro gaa Giu 510 att Ile att Ilie ace Th r gca Ala ate Ile ate Ile gag Giu 415 ett Leu eag Gin act Thr tee Se r gag Giu 495 tee Ser gtg Val1 ttg Leu ttg Leu ttg Leu 575 a tg Met aat Asn 400 egt Arg gtg Vai gee Ala ace Thr etc Leu 480 ggC Gly att Ile ctg Leu ceg Pro ggt Gly 560 aac Asn get Ala gaa Glu tte Phe gtc Val1 aae Asn gat Asp 465 aat Asn gtt Val gag Giu gee Al a geg Ala 545 at t Ile t te Phe att Ile acg Th r gae Asp ace Thr gaa Glu 450 gat Asp gag Glu gag Glu geg Ala act Thr 530 aag Lys etc Leu tee Ser att Ile tat Tyr gag Glu ggg Gly 435 gt t Val1 Gly cag Gin gt g Val etc Leu 515 tte Phe gee Ala ace Thr ct Pro tat Tyr eca Pro 405 ttt Phe gac Asp gga Giy a cg Thr gt g Val1 485 ate Ile gaa Giu etc Leu ate Ile atg Met 565 tea Pro ctt Leu 1267 1315 1363 1411 1459 1507 1555 1603 1651 1699 1747 1795 1843 1891 1939 590 595 tee ace gae tat gag gtg tte etg gta tet ege atg gtg gag gee ege WO 01/00804 PCT/1BO0100922 Ser Thr Asp Tyr Glu Val Phe Leu Val Ser Arq Met Val Glu Ala Arg 600 605 610 gat aaa ggc gaa icc acc gac gac gc-c atc aga tac ggc act gca cac 1987 A-sp Lys Gly Giu Ser Thr Asp Asp Ala Ile Arg Tyr Gly Thr Ala His 615 620 625 acc gga tct atc atc acc gcg gcc qca ctg atc atg att gtg gtc tgt 2035 Thr Gly Ser Ile Ile Thr Ala Ala Ala Leu Ile Met Ile Val Val Cys 630 635 640 645 gga gcg ttt ggt ttc tct gag aic gtc atg atg aag tac atc gcg tic 2083 Gly Ala Pbe Gly Phe Ser Glu Ile Val Met Met Lys Tyr Ile Ala Phe 650 655 660 ggc atg atc gca gcq ctg att ctg gat gcc acc atc atc cgc atg ctg 2131 Gly Met Ile Ala Ala Leu Ile Leu Asp Ala Thr Ile Ile Arg Met Leu 665 670 675 cit gtc ccc cgc cgt gat gca cct gct tcg cga cga caa ctg gtg ggc 2179 Leu Val Pro Arg Arg Asp Ala Pro Ala Ser Arg Arg Gin Leu Val Gly 680 685 690 acc cgg ctt cgt taaaaaggcc tacaccgtca tgg 2214 Thr Arg Leu Arg 695 <210> 226 <211> 697 <212> PRT <213> Corynebacterium giutamicun <400> 226 Val Phe Ser Lys Trp Gly His Phe Ala Tyr Arg Phe Arg Arg Ile Val 1 5 10 Pro Leu Val Val Ile Ala Ala Ile Leu Ala Leu Phe Val Ile Phe Gly 25 Thr Lys Leu Gly Asp Arg Met Ser Gin Giu Gly Trp Asp Asp Pro Gly 40 Ser Ser Ser Thr Ala Ala Ala Arg Ile Glu Leu Glu Thr Phe Gly Arg 55 Asp Asn Asp Gly Asp Val Val Leu Leu Phe Thr Ala Pro Glu Gly Thr 70 75 Ser Phe Asp Asp Ala Giu Val Phe Ser Ser Ile Ser Gly Tyr Leu Asp 90 Gly Leu Ile Giu Asn Asn Pro Asp Giu Val Ser His Ile Asn Ser Tyr 100 105 110 Phe Asp Thr Arg Asn Gin Asn Leu Leu Ser Lys Asp Gly Thr Gin Thr 115 120 125 WO 01/00804 WO 0100804PCT/IBOO/00922 Phe Ala Ala Leu Gly Leu Phe 145 ValI Glu Phe Ala Ille 225 S er Phe Glu Phe Pro 305 Gly Met Thr Ala Leu 385 Glu 130 Arg Thr Gly Val Met 210 Leu Val Met Gin Ser 290 Gin Leu Leu Ala Met 370 Al a Th r Glu Thr Met Al a 195 Pro Al a Val Val Al a 275 Al a Al a Al a Gly Ar g 355 Arg Leu Tyr I le Giu Al a 180 Ile Leu Ile Thr Ser 260 Val1 Al a Phe Ala Lys 340 Arg His Thr Leu Glu Val 165 Giy Leu Ile Leu Leu 245 Arg Al a Met Leu Leu 325 Asn Leu Al a ValI Pro IAsp 150 Al a Asp Leu Val Ala 230 Leu Phe Thr Val1 Lys 310 Met Ile Glu Lys Pro 390 Pro Lys 135 Gin Gly Ile Leu Gly 215 GI y GI y Arg Thr Ala 295 Ser Ser A.sp Isp 375 ,eu lia Let.
Ala Se r Ile 200 Ile Phe Leu Glu Thr 280 Val Val1 Val1 Lys Thr 360 Val Thr As n His Thr Arg 185 Val Leu Phe Gly Glu 265 Al a Al a Ala Thr Trp 345 Ile Thr Gl y Asp Giy'Asp Giy Glu Gin Thr Leu Lys Asp Pro Asp 155 Ala Val 170 Ala Glu Phe Gly Ser Ile Gin Val 235 Leu Ala 250 Met Asp Thr Ala Leu Ser Phe Gly 315 Vai Leu 330 Ser Leu Trp Tyr Vai Gly Val Lys 395 Thr Arg 410- As n Al a Val1 Ser Leu 220 As n Ile Lys Gly Gly 300 Al a Pro Arg Arg Val 380 Phe Val1 Leu Asp Phe Val 205 Gly Val Asp Gly Lys 285 Leu Ile Ser Arg Val1 365 Vai GI y Ala Al a Ala Ala 190 Val Ser Phe Tyr Th r 270 Thr Phe Ser Leu Thr 350 Pro Leu GI y Gin Gly Gly 160 Leu Asp 175 Leu Pro Ala Ala Leu Gly Ala Gin 240 Gly Leu 255 Pro Val Val Val Val Phe Ala Val 320 Phe Ser 335 Ala Arg Ala Trp Leu Leu Ile Asn 400 Giu Arg 415 405 Phe Asp Glu Phe Ap Glu Phe Pro Ala Phe Arg 425 Thr Giu Pro Val Lys Leu Val 430 WO 01/00804 WO 0100804PCT/IBOO/00922 Val Thr Gly 435 Asn Glu Val 450 Asp Asp Gly 465 Asn Glu Gin Val Glu Val Glu Ala Leu 515 Ala Thr Phe 530 Ala Lys Ala 545 Ile Leu Thr Phe Ser Pro Ile Ile Tyr 595 Met Val Glu 610 Tyr Gly Thr 625 Met Ile Val Lys Tyr Ile Ilie Ilie ArgI 675 Ala Asp Asn Asn Gin Leu Ile Asp Ile Giu Thr ValI Gin 500 Phe Ilie Ilie Leu Gly 580 Gly Al a Al a Val Ala 660 Met Gly Thr Val1 485 Ile Glu Leu Ile Met 565 Pro Leu Axg His Cys 645 Phe Leu Leu ValI 470 Glu Gly Lys Met Met 550 Phe Leu Ser Asp Thr 630 Gly Gliy Leu Th r 455 Leu Gin Gly Leu Ala 535 Thr Val1 Met Thr Lys 615 Gly Ala Met Val1 Asp Ser Leu Th r Leu 520 Leu Ile Asp Ser Asp 600 Gly Se r Phe Ile Pro 680 Arg Thr Arg Pro 505 Trp ValI Leu Gly Pro 585 Tyr Glu Ile Gly Ala 665 Arg Phe Gly Ala 490 Ala Met Phe Gly Val1 570 Val1 Glu Ser Ile Phe 650 Ala Arg Thr Ile 475 Ile Met Al a Gi y Met 555 Gi y Leu ValI Thr Th r 635 Ser Leu Asp Al a 460 Gin Ser Giu Leu Se r 540 Gly Ala Val Phe Asp 620 Ala Glu Ile Ala Tyr 445 Gly Asp Val1 Ile Tyr 525 Val1 Ala Ser Leu Leu 605 Asp Al a Ile Leu Pro 685 Val Gin Ala Ala Arg Pro Glu 510 Ile Ile Thr Ala Ile 590 ValI Ala Al a Val1 Asp 670 Ala Thr Thr Ser Leu 480 Giu Gly 495 Ser Ile Val Leu Leu Pro Leu Giy 560 Leu Asn 575 Met Ala Ser Arg Ile Arg Leu Ile 640 Met Met 655 Ala Thr Ser Arg Arg Gin Leu Val Gly Thr 690 Arg Leu Arg 695 <210> 227 <211> 729 <212> DNA <213> Corynebacterium glutamicum WO 01/00804 WO 0100804PCT/IBOO/00922 <220> <221> CDS <222> (706) <223> RXN03042 <400> 227 atgacaccgg cgcgacgtat ggcattactg gcgtacccca atttacgatg acatctctgc tcgcctcgge gacgtectgg ttecttacgt tetgatcgtt ttg gtt cta gcg tte Leu Val Leu Ala Phe ct C Leu get Ala gcg Ala ctq Leu gc Ala ace Th r gg t Gly geg Ala get Ala att Ile 150 gtg Val.
ctg Leu ate Ile ctg Leu atg Met aag Lys gee Ala gca Ala ct g Leu 135 ate Ile ctg ttg Leu Leu ggC ttt Gly Phe ttc caa Phe Gin tcc ttc Ser Phe gat tac Asp Tyr ggc aag Gly Lys cgc gtg Arg Val 105 ttc ata Phe Ile 120 gcc gtt Ala Vai eet gea Pro Ala etc Leu ggc Gly gaa Glu t tg Leu Gag Gin act Th r gte Val1 geg Ala get Ala aea Thr gtg Val ttg Leu ggt Gly ceg Pro ate Ile 75 geg Al a act Thr cag Gln gt g Val1 atg Met 155 tte Phe tea Ser get Ala ate Ile 60 ttc Phe ggc Gly get Ala gac Asp tte Phe 140 tte Phe egg Arg gt t Va].
ttc Phe 45 atg Met etc Leu aac As n geg Ala atg Met 125 tte Phe ctg Leu tc Ser et g Leu 30 9gc Gly etc Leu gtt Val gca Al a geg Al a 110 geg Ala gat Asp et t Leu att Sle 15 get *Ala ate Sle ate Ile act Th r aeg Thr 95 ctg Leu ttt Phe gee Al a gat Asp t gg T rp ace Thr ate Ile Gly cgt Arg 80 t eg Ser ate Ile at t Ile tte Phe gae Asp 160 1 gte Val1 ttt Phe gac Asp etg Leu a tg Met aat As n atg Met aag Lys gt t Val 145 aag Lys eea Pro gg t Gly gat Asp gta ValI cgt Arg ggt Gl y gt g Val1 ace Thr 130 gt t Val1 get Ala ttg Leu get Ala cct Pro tt t Phe gag Glu ttC Phe tet Ser 115 atg Met ege Arg tgg Trp ate Ile ace Thr cag Gin ggt Gly ggC Gly aag Lys 100 g tg Val1 Gly atg Met tg Trp geg Al a gtg Val1 eca Pro etg Leu ttc Phe eac His ttC Phe ttt Phe atg Met eta Leu 165 163 211 259 307 355 403 451 499 547 595 643 cet aag tgg Pro Lys Trp ttg gat Leu Asp 170 aag att ctt eec aae gtt gat gtt gaa Val Asp Val Giu Lys Ile Leu Pro Asn 175 ggt gag Gly Giu 180 WO 01/00804 PCT/IBOO/00922 ggt ctt agt gaa cta cat gag qct cgc acc gag gaa ctg aag gaa aat 691 Gly Leu Ser Glu Leu His Glu Ala Arg Thr Glu Glu Leu Lys Giu Asn 185 190 195 gta ggt gtc ggg gct tagagaaaca aaaaaggctg cta 729 Val Gly Val Gly Ala 200 <210> 228 <211> 202 <212> PRT <213> Corynebacterium giutamicum <400> 228 Leu Val Leu Ala Phe Leu Val Leu Leu Leu Val Phe Arg Ser Ile Trp 1 5 10 Vai Pro Leu Ile Ala Ala Leu Gly Phe Gly Leu Ser Val Leu Ala Thr 25 Phe Gly Ala Thr Val Ala Ile Phe Gln Giu Gly Ala Phe Gly Ile Ile 40 Asp Asp Pro Gin Pro Leu Leu Ser Phe Leu Pro Ile Met Leu Ile Gly 55 Leu Val Phe Gly Leu Ala Met Asp Tyr Gin Ile Phe Leu Val Thr Arg 70 75 Met Arg Glu Gly Phe Thr Lys Gly Lys Thr Ala Gly Asn Ala Thr Ser 90 Asn Gly Phe Lys His Gly Ala Arg Val Val Thr Ala Ala Ala Leu Ile 100 105 110 Met Val Ser Val Phe Ala Ala Phe Ilie Ala Gln Asp Met Ala Phe Ile 115 120 125 Lys Thr Met Gly Phe Ala Leu Ala Val Ala Val Phe Phe Asp Ala Phe 130 135 140 Vai Val Arg Met Met Ile Ile Pro Ala Thr Met Phe Leu Leu Asp Asp 145 150 155 160 Lys Ala Trp, Trp Leu Pro Lys Trp Leu Asp Lys le Leu Pro Asri Val 165 170 175 Asp Val Giu Gly Giu Gly Leu Ser Glu Leu His Giu Ala Axg Thr Giu 180 185 190 Giu Leu Lys Glu Asn Val Gly Val Gly Ala 195 200 <210> 229 <211> 729 WO 01/00804 <212> DNA <213> Corynebacteriusi giutamicum <220> <221> CDS <222> (706) <223> FRXA02893 <400> 229 atgacaccgg cgcgacgtat ggcattactg gcgiacccca PCT/IBOO/00922 atttacgatg acatctctgc tcgcctcggc gacgtcctgg ttccttacgt tctgatcgtt itg gtt cta gcg tic Leu Val Leu Ala Phe ctc Leu gc t Ala gcg Al a cig Leu gcc Ala acc Thr gt Gly gcg Ala gct Ala att Ile 150 ctg ttg Leu Leu ggc ttt Gly Phe tic caa Phe Gin tcc tic Ser Phe gat tac Asp Tyr ggc aag Gly Lys cgc gig Arg Val 105 itc ata Phe Ile 120 gcc gt Ala Val cci gca Pro Ala ctc gig Leu Val ggc tig Gly Leu gaa ggt Glu Gly ttg ccg Leu Pro cag atc Gin Ile 75 act gcg Thr Ala gic act Val Thr gcg cag Ala Gln gct gig Ala Val aca aig Thr Met 155 tc Phe t ca Ser gci Ala atc Ile tic Phe ggc Gly gct Ala ga c Asp tic Phe 140 tic Phe c99 Arg gt Val1 tic Phe 45 aig Met ctc Leu aac Asn gcg Ala aig Met 125 tc Phe ctg Leu icc at Ser Ile 15 ctg gci Leu Ala 30 ggc aic Gly Ile cic aic Leu Ile git act Val Thr qca acg Ala Thr gcg cig Ala Leu 110 gcg iii Ala Phe gat gcc Asp Ala ctt gat Leu Asp 1 tgg gic Trp Val acc ttt Thr Phe aic gac Ile Asp ggc cig Giy Leu cgt aig Arg Met 80 tcg aai Ser Asn aic atg Ile Met ait aag Ile Lys tic gt Phe Val 145 gac aag Asp Lys 160 cca tig Pro Leu ggt gci Gly Ala gat cci Asp Pro gia iii Val Phe cgt gag Arg Glu ggt tic Gly Phe gig ict Val Ser 115 acc aig Thr Met 130 gtt cgc Val Arg gci tgg Ala Trp gcg Al a gt g Val1 cca Pro ci g Leu tiC Phe cac His tic Phe iii Phe aig Met cia Leu 165 cci aag tgg itg gat aag ati cii ccc aac gti Pro Lys Trp Leu Asp Lys Ilie Leu Pro Asn Val gat git gaa ggi gag Asp Val Giu Gly Giu WO 01/00804 ggt ctt agt Gly Leu Ser gta ggt gtc Val Gly Val 200 PCTIIBOO/00922 175 180 cat gag gct cgc acc gag gaa ctg aag qaa aat 691 His Giu Ala Arg Thr Glu Glu Leu Lys Giu Asn 190 195 tagaqaaaca aaaaaggctg cta 729 <210> 230 <211> 202 <212> PRT <213> Corynebacterium glutamicum <400> 230 Leu Val Leu Ala Phe Leu Val Leu 1 Val1 Phe Asp Leu Met Asn Met Lys Val 145 Lys Asp Pro Gly Asp Val1 Arg Gly Val Th r 130 Val1 Ala Val1 Leu Ala Pro Phe Gi u Phe Ser 115 Met Arg Trp Gi u lie Thr Gin Gly Gly Lys 100 Val Gly Met Trp Gly 180 5 Al a Val1 Pro Leu Phe His Phe Phe Met Leu 165 Glu Ala Ala Leu Ala Thr Gly Ala Ala Ile 150 Pro Gly Leu Ile Leu 55 Met Lys Al a Ala Leu 135 Ile Lys Leu Gly Phe 40 Ser Asp Gi y Arg Phe 120 Al a Pro V rp Ser Leu Leu 10 Phe Gly 25 Gin Glu Phe Leu Tyr Gin Lys Thr 90 Val Val 105 lie Ala Val Ala Ala Thr Leu Asp 170 Glu Leu 185 Phe Se r Al a Ile Phe Gly Ala Asp Phe 140 Phe I le Arg Val1 Phe Met Leu Asn Al a Met 125 Phe Leu Leu Ser Ile Leu Ala Gly Ile Leu Ile Vai Thr Ala Thr Ala Leu 110 Ala Phe Asp Ala Leu Asp Pro Asn His Glu Ala Arg Thr Glu 190 Glu Leu Lys 195 Glu Asn Val Gly Val Gly Ala 200 WO 01/00804 <210> 231 <211> 1605 (212> DNA <213> Corynebacterium giutamicum <2 <221> CDS <222> (1582) <223> RXA01616 <400> 231 cctacgattt ccgacgtctt aaatcgccac acagcgccqt PCTIIBOO/00922 ggtctaaaac accaacaaaa gagttgtaac tgtaccgacc attcgttaca gttacgatcc atg act tca gaa acc Met Thr Ser Glu Thr tta Leu gt t Val1 tac Tyr caa Gin cgt Arg ttc Phe ttt Phe ate Ile a cg cag Gin atc Ile a cc Thr gcg Ala ttg Leu ctc Leu g Ct Ala ggt Giy ttt gcg Ala agc Ser gca Al a ttg Leu ggt Gly atg Met C Ca Pro gcg Ala 120 gag caa Gin ggt Gly et c Leu t gg Trp gee Ala Gly act Thr 105 gca Ala gat gcg Ala ggt GI y cct Pro ate Ile Gly ttg Leu gcg Al a a cg Thr gag cct Pro etc Leu ctg Leu ate Ile act Th r 75 agc Se r tgg Trp a tg Met cgt *acg Thr *ttt Phe ctg Leu aac Asn 60 ttg Leu att Ile get Ala atg Met gag aaa Lys ctg Leu cg t Arg 45 gca Ala ggt Gly ttC Phe ctt Leu cct Pro 125 gc ace Thr ate Ile 30 gaa Giu tat Tyr gac: Asp gga Gly gt t Val 110 gca Ala aac Asn caa Gl n 15 gg t Gly cag Gln cCC Pro aaa Lys ate Ile 95 get Ala ace rhr a ct T'hr cgt Arg gta Val1 etc Leu ctg Leu aac Asn 80 get Ala gcg Ala ttg Leu gca Al a 1 tgg Trp gac Asp g ca Ala Ct c Leu ggc Gly tca Ser aga Arg get Al a att Ile 145 gct Ala aac As n gcc Ala a tg Met: cac His ctt Leu get Al a ct g Leu 130 gt Gly ttc Phe t cg Ser tee Ser g Cg Ala cgc Arg ggt Gi y ttC Phe 115 ate Ile att Ile etc Leu 20 att I le gaa Glu ggc Gi y Arg get Ala 100 ct t Leu cgc Arg tgg Trp gcc Al a c Leu ace Th r Ctt Leu atg Met gcg Ala 9gc Gly att Ile ggt Gi y 115 163 211 259 307 355 403 451 499 547 Thr Phe Glu Asp Glu Arg Glu Arg tC Ser 150 qtg gca att ctt Val Ala Ile Leu ggc gct gcg gca ggc ccg Gly Ala Ala Ala Gly Pro 155 160 atc att ggt ggt gcg Ile Ile Gly Gly Ala WO 01/00804 WO 0100804PCT/IBOO/00922 ctg ttg gaa ttc ttc tgg tgg ggt tcg gtt ttc etc att aac Leu Leu Giu Phe Phe Trp Trp Gly Ser Val Phe Leu Ile Asn gtt cog Val Pro gtg Val1 atc Ile ct g Leu act Thr 230 att Ile ctt Leu gt t Val a cc Thr ggt Gly 310 atc Ile ggt Gly gcg Al a atg Met gct Ala gcg A1a ctc Leu 215 gca Al a ggt Gl y cta Leu got Al a t cg Ser 295 ttg Leu ggt Gly ggt di y act Th r ggC Gly gtt Val1 aat Asn 200 aca Thr cgc Arg gog Ala ga t Asp gcg Ala 280 cag Gin oto Leu ggt Gly ttt Phe oat His 360 gcg Ala ate Ile 185 0 cg Pro ott Leu cat His gt g Val1 ot g Leu 265 ggo Gly cgt Arg atg Met gca Ala got Ala 345 act Thr ggt dl y 170 *Ala tot *Ser got Al a atg Met ttg Leu 250 tog Se r atg Met tto Phe atc Ile aao Asn 330 gc Ala ga t Asp got Ala ttg ate Leu Ile aag oat Lys His ggg ttg Gly Leu 220 cot ott Pro Leu 235 ttt ago Phe Ser ttg tto Leu Phe gog atg Ala Met cag ttg Gin Leu 300 oca got Pro Ala 315 otg oat Leu His act gcc Thr Ala ggt ttg Gly Leu ggt tog Gly Ser 175 180 got Ala t gg Trp 205 ato Ile ott Leu agt Se r ogt Arg ttt Phe 285 tot Ser gca Ala cgt Arg gtt Val cog Pro 365 gt a Val1 a og i hr 190 ga t Asp at c Ile ttg Leu cg t Arg aat Asn 270 act Thr gtg Val ttg Leu tgg Trp ggc Gl y 350 ttt Phe atg Met ott Leu ttc Phe aog Thr ggt Gly cag Gin 255 ogo Arg gtg Val ggt Gly ggt Gly ggc GI y 335 atc Ile tto Phe tot Ser ttt qtg Phe Val ttg tog Leu Ser ato aag Ile Lys 225 goa gto Ala Val 240 aag aag Lys Lys ott ttc Leu Phe too ggt Ser Gly tto act Phe Thr 305 ago ttc Ser Phe 320 tto aaa Phe Lys goc otg Ala Leu atc gog Ile Ala gtg tot Val Ser gog Al a tog Ser 210 gaa Glu ato Ile ato Ile t ta Leu t tg Leu 290 cca Pro cog Pro cog Pro tgt Cys ggt Gly 370 too Ser 691 739 787 835 883 931 979 1027 1075 1123 1171 1219 1267 1315 375 380 385 ato ggt too gog cog gtg ogt aag got ggc atg qog tog tog ato gaa WO 01/00804 Ile Gly Ser Ala Pro Val Arg Lys Ala Gly 390 395 gag gtc tct tat gag ttc ggc acg ctg ttg Glu Val Ser Tyr Giti Phe Gly Thr Leu Leu 410 415 agc ttg ttc cca ttc ttc tac tcg ctg cat Ser Leti Phe Pro Phe Phe Tyr Ser Leu His 425 430 qat aac ttc tcg gcg ggt qtt cac cac qcg Asp Asn Phe Ser Ala Giy Val His His Ala 440 445 cgt gca tct ttg gac acc gca tac att aac Arg Ala Ser Leu Asp Thr Ala Tyr Ile Asn 455 460 gta tgc gca gta gcg gct gct ctg atc agc Val Cys Ala Val Ala Ala Ala Leu Ile Ser 470 475 aat ccg aag gga gcc aat aat gcg cac tagi Asn Pro Lys Gly Ala Asn Asn Ala His 490 tgc <210> 232 <211> 494 <212> PRT <213> Corynebacterium glutamicum <400> 232 Met Thr Ser Giti Thr Leu Gin Ala Gin Ala 1 5 Trp Ala Phe Leu Ala Val Ile Ser Gly Gly Asp Asn Ser Ilie Leti Tyr Thr Ala Leu Pro 40 Ala Ala Ser Glu Thr Gin Ala Leu Trp Ilie 55 Leu Met Ala Gly Leu Arg Leu Gly Ala Gly 70 Gly His Arq Arg Met Phe Leu Met Gly Leu Ser Leu Gly Ala Ala Phe Ala Pro Thr Ala 100 105 PCT/IBOO/00922 Met Ala Ser Ser Ile 400 tct gtc gcg att ttg Ser Val Ala Ile Leti 420 gcc ccg gca gag gtt Ala Pro Ala Giu Val 435 att gat ggc gat gcg Ile Asp Gly Asp Ala 450 gtg ttg atc att gcc Val Lei Ile Ile Ala 465 agt tac ctt ttc cgc Ser Tyr Leti Phe Arg 480 taaaaaa gagatgattc Pro Thr Leu Phe Leu Leti Ile Asn Thr Leti 75 Ser Ile Trp Ala Lys Leu Arg Ala Gi y Phe Leu Giti 405 ggt Gi y gcg Al a gcg Al a ct a Leu gga Gly 485 Arg Val1 Leu Leu Asn Ala Al a 1363 1411 1459 1507 1555 1602 1605 Ar Al Ii, 14 Ill Let Val Ser Lys 225 Val Lys Phe Gly Thr 305 Phe Lys Leu Ala Ser 385 Al a WO 01/00804 g Ala Phe Li 115 a Leu Ile A~ 130 Gly Ile T~ 5 Ile Gly Gl Ile Asn Va 18 Ala Pro Al 195 Ser Phe Ty 210 Glu Ser Va Ile Met Le' Ile Glu Gli 26~ Leu Gly Gl~ 275 Leu Glu Met 290 Pro Leu GIl Pro Met Ser Pro Leu Ile 340 Cys Ile Trp 355 Gly Leu Phe 370 Ser Thr Ala Ser Ser Ile eu Gly rg Ile :p Gly -y Ala 165 1i Pro 0 a Asn r Ala 1 Asn u Ile 245 u Pro 0 ~Val I Thr TI Ala G 3 Ile I 325 Ser G Gly A Phe Mi Ile I: 3c Glu G] 405 Ii Th Se 15 Le Va.
Il Lei Thr 230 Ile Leu l hr 1 y 10 le ly la et le e Gly Ala 120 r Phe Glu 135 r Val Ala 0 u Leu Gin 1 Ala Val SAla Asn 200 Leu Thr 215 Ala Arg Gly Ala Leu Asp Ala Ala 280 Ser Gin 1 295 Len Leu Gly Gly A Gly Phe A 3 Thr His T 360 Gly Ala G 375 Gly Ser A.
Val Ser T~
A:
Ii Ph~ Ii 18 Pr Le Hi Va, Let 26! ~et la l1a 45 hr ly la la Th ;p GI "e Le "e Ph 17' e Al 5 Sei Alz Met 1 Leu 250 u2 Ser 5 ~Met Phe Ile Asn 330 Al a Asp Ala Pro Glu 410 r Met Met Pro Ala 125 Arg Glu Arg Asn 140 Gly Ala Ala Ala 155 Trp Trp Gly Ser 0 Len Ile Ala Thr 190 *Lys His Trp Asp 205 Gly Len Ile Ile 220 Pro Leu Leu Leu 235 Phe Ser Ser Arg Leu Phe Arg Asn 270 Ala Met Phe Thr 285 Gin Leu Ser Val 300 Pro Ala Ala Leu 315 Leu His Axg Trp C Thr Ala Val Gly I 350 Gly Leu Pro Phe P 365 Gly Ser Val Met S 380 Val Arg Lys Ala G 395 Phe Gly Thr Len L Th Th.
Va 17! Let PhE Thi Gly Girt 255 Arg Val Gly ,ly le 'he er ly eu PCT/IBOO/00922 r Len r Ala y Pro 160 1 Phe aPhe Leu Ile Ala 240 Lys Len Ser Phe Ser 320 Phe Al a I le Val Met 400 Ser 4 WO 01/00804 PCTIIBOO/00922 Val Ala Ile Leu Gly Ser Leu Phe Pro Phe Phe Tyr Ser Leu His Ala 420 425 430 Pro Ala Glu Val Ala Asp Asn Phe Ser Ala Gly Val His His Ala Ile 435 440 445 Asp Gly Asp Ala Ala Arg Ala Ser Leu Asp Thr Ala Tyr Ile Asn Val 450 455 460 Leu Ile Ile Ala Leu Val Cys Ala Val Ala Ala Ala Leu Ile Ser Ser 465 470 475 480 Tyr Leu Phe Arg Gly Asn Pro Lys Gly Ala Asn Asn Ala His 485 490 <210> 233 <211> 1500 <212> DNA <213> Corynebacteriwn glutamicun <220> <221> CDS <222> (1477) <223> RXA01666 <400> 233 cgacgcgccc ctccaccttt tcagtagcgt cacgggcgcc agtttgaggg tttttgctcc ccatctttag gagacacccc aaa Lys ttc Phe ctg Leu tcc Ser atg Met ctg Leu ttg Leu gcc Ala ggc Gly ttt Phe t tt Phe tgg Trp atc Ile gt g Val1 at c Ile ttc Phe t cc Ser gt g Val1 atg atc Met Ilie tgg atg Trp Met gga att Gly Ilie 45 gtt gtt Val Val acc aca Thr Thr ctg gag Leu Glu t cc Se r tat Tyr 30 tac Tyr ga t Asp ct C Leu gaa Glu aac Asn ctt Leu atg Met cac His gtg ValI ga c Asp gtc Val1 tcc Ser ggt Gi y aat Asn ttt Phe 80 ggc Gly aatcctgtat ttttagcagc gtg tcc acg ttt cat Val Ser Thr Phe His 1 acc act gga ttt ctg Thr Thr Gly Phe Leu act ggc aac gtc gca Thr Gly Asn Val Ala ttg atc gcc gtt tgt Leu Ile Ala Val Cys cgc aag aag tcc gtc Arg Lys Lys Ser Val tat tgt ctc agt gcc Tyr Cys Leu Ser Ala ctg agc atc gga aat Leu Ser Ile Gly Asn 100 115 163 211 259 307 355 403 WO 01/00804 WO 0100804PCTIBOO/00922 ace gcc ctg tgg gtg ttc gtt Val Phe Val tct tte ate etc ate gga tea ate gtg Ser Phe Ile Leu Ile Gly Ser Ile Val Thr Ala Leu gaa cac Glu His cct gaa Pro Glu 135 ggt gtt Gly Val 150 ttc ttg Phe Leu gtc gcg Val Ala ate acc Ile Thr aca cct Thr Pro 215 gga tca Gly Ser 230 ttg ttt Leu Phe atg gac Met Asp ctg ctt Leu Leu tcc aaa Ser Lys 295 atg Met 120 gct Ala gga Gly gge Gly ctg Leu caa Gin 200 acc Thr a tg Met gcg Ala cet Pro gga Gly 280 act Thr Trp 105 egc Arg qaa Gliu ttt Phe atg Met ct g Leu 185 ga a Giu tee Ser aaa Lys tcC Ser tac Tyr 265 ct C Leu ggc Gly 110 115 *aac Asn egc Arg tta Leu ga a Glu 170 cac His gac Asp gat Asp atc Ile ttc Phe 250 gge Gly acc Thr ttg Leu atc gca Ile Ala gac aaa Asp Lys 140 gte ace Val Thr 155 ate acc Ile Thr ctg ctg Leu Leu gca eag Ala Gin ttg gcg Leu Ala 220 atc ctg Ilie Leu 235 aac aac Asn Asn etg gaa Leu Glu age etc Ser Leu ggc aaa Gly Lys 300 ttt gtt Phe Val ctg Leu 125 gca Al a age Ser etg Leu ceg Pro cct Pro 205 ate Ile ag t Se r ctc Leu ctt Leu ggc Gi y 285 aac Asn Gly tec Ser aac Asr gtc Val tgg Trp at t Ile 190 act Thr gt g Val1 gt t Val1 ate Ile ttC Phe 270 ttc Phe ect Pro atq Met ace Thr ggC Gly att Ile atc Ile 175 cgc Arg gtt Val1 tc Ser ccg Pro gge Gly 255 agc Ser atc Ile gtg Val tta Leu gt g Val1 ctg Leu gct Ala 160 t gc Cys gte Val1 tct Ser aaa Lys gga Gly 240 ggc Gi y c ca Pro gtt Val :gc lkrg ttt ?he gte Val gta Val 145 ggt Giy ct t Leu ga c Asp ga c Asp ggc Gly 225 ctg Leu gtg Val1 cag Gin gt Gly acc Thr 305 gce Ala acg Thr 130 gga Gi y tee Ser ggg Gly gaa Giu gat Asp 210 atc Ile ctc Leu tac Tyr etg Leu ggt Gly 290 ttg Leu att Ile ctg Leu gee Al a gee Ala etc Leu ccg Pro 195 tea Ser gac Asp geg Ala tee Ser tgg T rp 275 get Ala etg Leu ege Arg ttg Leu gtg Val1 ate Ile tea Ser 180 gaa Glu gtt Val1 eta Leu ct t Leu gea Al a 260 ggg Gly gtg Val1 ctg Leu gaa Glu gt t Val caa Gin ggg Gly 165 ett Leu ate Ile ec Pro aaa Lys gtg Val1 245 etc Leu eta Leu ate Ile qt t ValI t gg Trp 325 499 547 595 643 691 739 787 835 883 931 979 1027 1075 1123 aat gtt ggt gtg get Asn Val Gly Vai Ala 310 315 320 tgg tgg ete tac: ate etg gge att ttc ate ttC atg get ate aee cca Trp gct Ala cgc Arg qcc Ala ctc Leu 390 atc Ile tca Ser t cc Ser WO 01/00804 Trp Leu Tyr gcc gaa gcc Ala Glu Ala 345 caa caa ggc Gin Gin Gly 360 aac ccq ctc Asn Pro Leu 375 att cca tgg Ile Pro Trp ctc ggc gag.
Leu Gly Glu ggt gcc atc Gly Ala Ile 425 tac cgg aaa Tyr Axg Lys 440 PCT/IBOO/00922 Ile 330 gca Al a cgc Arg tcc Ser at g Met ggt Giy 410 atg Met ctc Leu Leu gaa Glu gta Vai aca Thr gct Aia 395 aaa Lys ttg Leu agc Se r Gly caa Gin ttt Phe gt g Val 380 ggc Gly gct Ala gt t Val1 cag Gin Ile Phe Ile 335 acc atc ctt Thr Ile Leu 350 gga cta gcc Gly Leu Ala 365 atc gtg gcg Ile Val Ala ccc ggc gcg Pro Gly Ala cgc ggc atg Arg Giy Met 415 gtc gtg ctg Val Vai Leu 430 tac tac gcc Tyr Tyr Ala 445 Phe ca a Gin atg Met att Ile gac Asp 400 gca Al a ttg Leu acc Ala gtc Val gtg Val 370 gcc Ala atc Ile atg Met ttc Phe agc Thr 340 cca Pro atg Met qcc Ala 9gC Gly ct C Leu 420 tcg Se r gac Asp 1171 1219 1267 1315 1363 1411 1459 1500 Thr Thr Ser Gin 450 gcg gga gct gct gag aag taagtgc Ala Gly Ala Aia Giu Lys 455 <210> 234 <211> 459 <212> PRT <213> Corynebacterium glutamicur <400> 234 Val Ser Thr Phe His Lys Val Leu 1 5 Thr Thr Gly Phe Leu Phe Phe Ala Thr Gly Asn Val Ala Leu Thr Gly 40 Leu Ilie Ala Val Cys Ser Ile Phe 55 Arg Lys Lys Ser Val Met Leu Phe 70 tct agaccgttgt ttg Ile Asn Thr Met Ile Ser Asn Val 10 Val Vai Phe Trp Met Tyr Leu Ser 25 Ile Val Ser Gly Ile Tyr Met Gly Phe Gly Thr Val Val Asp His Asn Ser Ser Val Thr Thr Leu Val Phe 75 wo 01/00804 WO 0100804PCT/IBOO/00922 Tyr Cys Leu Ser Ala Leu Val Trp Val Phe Trp Leu Glu Glu Asp Gly 90 Leu Ile Val1 Val 145 Gly Leu Asp Asp Gly 225 Leu Val1 Gin Gly Thr 305 Ala Met Ser Gly Thr 130 Gi y Se r Gly Giu Asp 210 Ile Leu Tyr Leu Gly 290 Leu Ile Ala Ile Se r 115 Leu Al a Al a Leu Pro 195 Ser Asp Al a Se r Trp 275 Ala Leu Arg Ile Gly 100 Ilie Le u Val1 Ile Ser 180 Giu Val1 Leu Le u Al a 260 Gly Val1 Le u Giu Thr 340 As n Val1 Val1 Gin Gly 165 Leu Ile Pro Lys ValI 245 Leu Leu Ile Val Trp 325 Pro Thr Gi u Pro Gly 150 Phe Val1 Ile Thr Gly 230 Leu Met Leu Ser As n 310 Trp Al a Ala His Giu 135 Vai Leu Ala Thr Pro 215 Ser Phe Asp Leu Lys 295 Val Trp Ala *Leu Met 120 Ala Gly Gi y Leu Gin 200 Thr Met Al a Pro Gly 280 Thr Gly Leu Glu Gin 360 Trp 105 Arg Glu Phe Met Leu 185 Glu Se r Lys Ser Tyr 265 Leu Gly Val1 Tyr Ala 345 Gly Val1 Asn Arg Leu Giu 170 His Asp Asp Ile Phe 250 Gly Thr Leu Ala Ile 330 Ala Arg Phe Ile Asp Val1 155 Ile Leu Al a Leu Ile 235 Asn Leu Ser Gly Phe 315 Leu Giu Val *Val Ala Lys 140 Thr Thr Leu Gin Ala 220 Leu Asn Glu Leu Lys 300 Val Gly Gin Phe Se r Leu 125 Ala Ser Leu Pro Pro 205 Ile Ser Leu Leu Gly 285 Asn Gly Ile Thr Gi y 365 Phe 110 Ser Asn Val1 Trp Ile 190 Thr Val Val Ile Phe 270 Phe Pro Met Phe I le 350 Leu Ile Thr Gly Ile Ile 175 Arg Val Ser Pro Gly 255 Se r Ile Val1 Leu Ile 335 Leu Ala Leu Val Leu Ala 160 Cys Val1 Ser Lys Gly 240 Gly Pro Val1 Arg Phe 320 Phe Gin Met Arg Val Val Pro Phe Arq Gin 355 Ala Val Glu Met Ala Ala Asn Pro Leu Ser Thr Val Ile Val Ala Ile WO 01/00804 Leu Ala Glu Ala Tyr Leu Ile Pro Trp Met Ala 385 390 395 Thr Ile Trp Gly Val Ile Leu Gly Glu Gly Lys 405 410 Leu Met Phe Leu Ala Ser Gly Ala Ile Met Leu 420 425 Ala Phe Met Ser Arg Ser Tyr Arg Lys Leu Ser 435 440 Thr Ser Gin Asp Ile Ala Gly Ala Ala Glu Lys 450 455 <210> 235 <211> 1521 <212> DNA <213> Cory-nebacterium glutamicum <220> <221> CDS <222> (1498) <223> RXA00062 <400> 235 cttcaacata ggegttgggg ctgactttta aacaggtacc tcactgttgc gttttcttgc tgccatcaaa aattagtcac PCT/IBOO/00922 Gly Pro Gly Ala Asp 400 Ala Arg Gly Met Ala 415 Val Val Val Leu Leu 430 Gin Tyr Tyr Ala Thr 445 gte ValI acg Thr ctg Leu ctg Leu tac Tyr tct Ser ctt Leu ggt Gi y tca Ser ctg Leu att Ile c ea Pro ggC Gly cct Pro gtg Val get Al a ctc Leu get Ala ttc Phe ate Ilie agt Ser gcc Ala ttg Leu 75 gte Val1 att Ile agt Se r tae Tyr gat Asp geg Ala att Ile ctg Leu gaa Glu 30 aea Thr ate Ile get Al a gga Giy ga e Asp gge Gly gte Val 9ge Gly t eq Ser 80 ege Arg agtagtaceg geataagega atg att tta agc atc Met Ile Leu Ser Ile 1 ace tee ate gte att Thr Ser Ilie Val Ile ate gat eec gtg eac Ile Asp Pro Val His tte gge gca ctt eti Phe Gly Ala Leu Leu ega aag aaa gtg etc Arg Lys Lys Val Leu ttg gca att geg ctt Leu Ala Ile Ala Leu gta gtt caa ggc geg Val Val Gin Gly Ala 100 115 163 211 259 307 355 403 gga Gi y ttc Phe gtt Val got Ala 150 gcc Ala ago Ser ggt Gi y tgg Trp ttc Phe 230 ccc Pro cgc Arg cag Gin gcg Ala cca Pro 310 WO 01/00804 got gog att Ala Ala Ilie 105 ccc gaa ggo Pro Glu Gly 120 gcc ggc atc Ala Gly Ilie 135 gat ott tig Asp Leu Leu gca gtg ttg Ala Val Leu agg cct gga Arg Pro Gly 185 atc gcc gog Ile Ala Ala 200 aca gat ccg Thr Asp Pro 215 atc tgg tic Ile Trp Phe otg ggg ctc t Leu Gly Leu 1 itt ctt ctg q Phe Leu Leu 265 ctg ttc cag g Leu Phe Gin A 280 ttc atg ccg c Phe Met Pro L 295 cgg ott too 0 Arg Leu Ser A atc Ile cca Pro ggt Gi y t cg Sex gc Al a 170 tca Ser ;i g Val ~ttt Phe z:tg eu :tt 'he ~tt 'al rac ~sp :ta .eu ga rg got Al gct Ala gic Val tgg Trp 155 ta c Tyr ctc Leu Ct C Leu gtg Val cgc Arg 235 aaa Lys ggo Gly acc Thr tot Ser gca Al a 315 -cca Pro -cgo Arg gca *Ala 140 cqc Arg ata Ile *gac Asp t ac Tyr ttg Leu 220 cat His aac Asn icc Ser atg Met ctg Leu 300 ggo Gly gcg Al a ct t Leu 125 gca Al a atc Ile qt g Val ato Ile gca Al a 205 at t Ile gaa Glu ogc Arg gtg Val1 gga Gly 285 ct g Leu gta lal aca Thr 110 cg t IArg Gly ggC Gly cac His to Phe 190 at Ile *i C Ser too Ser a gg Arg aig Met 270 atg Met cag1 GinI tot Ser cit Leu got Ala cta Leu tc Phe aaa Lys 175 gga Gi y gtc Val1 ot 0 Leu i ca Ser cga Arg 255 tca Se r aat Asn ~ti Phe lat ksp gog Ala aco Thr gig IVal ttt Phe 160 gco Ala goa Ala cgc Arg gtq Val gco Ala 240 aao Asn tc Phe gct Ala gcc Ala too Ser 320 tt q Leu tot Ser atc I le 145 atc Ile att Ile ati Ile ago Se r ci g Leu 225 aaa Lys a cc Thr tic Phe cto Leu agc Ser 305 atg let att Ile got Ala 130 ggo Gly aao Asn 000 Pro aoo Thr gc Ala 210 ggo Gly gaa Glu ato Ile tic Phe ca g Gln 290 9oo APla cto Leu act Thr 115 tat Tyr ggc Gi y gt 0 Val1 goa Ala too Ser 195 gat Asp aic Ile cca Pro itg Leu tt Phe 275 gca Ala gcg Ala aoo Thr gag Giu ggi Gly gta ValI 000 Pro acc Thr 180 acg Thr tao Tyr gca Ala Ott Leu goo Al a 260 gc Ala ggc Gly atg Met gtc ValI tc Phe got Ala ttt Phe aic Ile 165 to Phe gca Al a ago Ser gig Val ci g Leu 245 ago Ser aco Thr ott Leu gtg Val1 ato Ile 325 PCTIBOO/00922 451 499 547 595 643 691 739 787 835 883 931 979 1027 1075 1123 qg tic gcc atc aig gic ato ggc aig gca. ggo oto goa itt gta oca WO 01/00804 WO 0100804PCT/IBOO/00922 Gly Phe Ala Ile Met Val Ile Gly Met Ala Gly Leu Ala Phe Val Pro 330 335 340 aac acg Asn Thr caa ggc Gin Gly ccg aag Pro Lys 375 caa atc Gin Ile 390 get. gte Ala Val eac ttc His Phe ttt gcg Phe Ala atg atc Met Ile 345 tte gct Phe Ala 360 gac caa Asp Gin Gly Gly atc gga Ile Giy gga ttc Gly Phe 425 gte aca Val Thr 440 gcg Al a ttc Phe tcc Ser acc Thr cat His 410 ttg Leu ctg Leu ctg ate Leu Ile gga cca Gly Pro ggc gcc Giy Ala 380 ttC ggt Phe Gly 395 gat gca Asp Ala ctc tcc Leu Ser ctg aag Leu Lys eta Leu atg Met 365 gt t Val1 ttg Leu aca Thr acc Thr cgc Arg 445 ata Ile get Ala ggc Gly gtg Val1 gag Glu 415 acg Thr gaa Glu ttg Leu gca Ala gtg Val 385 tce Ser atc Ile a cg Thr cga Arg gga Gly 355 caa Gin tee Se r ttg Leu ga c Asp gcc Al a 435 agt Ser 1171 1219 1267 1315 1363 1411 1459 1508 1521 ege eca ace cag etc gte gac gaa aag gca gtt acc tet tagtgcgctg Arg Pro Thr Gln Leu Val Asp Glu Lys Ala Val Thr Ser 455 460 465 cageatecca gtt <210> 236 <211> 466 <212> PRT <213> Corynebacterium glutamicum <400> 236 Met Ile Leu Ser Ile Val Leu Leu Gly Tyr Phe Met Ile Leu Leu Asp 1 5 10 Thr Ser Ile Val Ile Thr Gly Leu Pro Ala Ile Gly Ser Glu Leu Gly 25 Ile Asp Pro Val His Leu Ser Trp Val Gin Ser Ser Tyr Thr Leu Val 40 Phe Gly Ala Leu Leu Leu Leu Gly Ala Arg Ala Gly Asp Ile Phe Gly 55 Arg Lys Lys Val Leu Tyr Ile Gly Leu Ala Leu Phe Ala Ala Ser Ser WO 01/00804 PCTIIBOO/00922 70 75 Leu Ala Ile Ala Leu Ser Pro Asn Ala Ala Val Leu Ilie Gly Ala Arg 90 Val Val Gln Gly Ala Gly Ala Ala Ile Ile Ala Pro Ala Thr Leu Ala 100 105 110 Leu Ile Thr Glu Phe Phe Pro Glu Gly Pro Ala Arg Leu Arg Ala Thr 115 120 125 Ser Ala Tyr Gly Ala Val Ala Gly le Gly Val Ala Ala Gly Leu Val 130 135 140 Ile Gly Gly Val Phe Ala Asp Leu Leu Ser Trp Arg Ile Gly Phe Phe 145 150 155 160 Ile Asn Val Pro Ile Ala Ala Val Leu Ala Tyr Ile Val His Lys Ala 165 170 175 Ile Pro Ala Thr Phe Ser Arg Pro Gly Ser Leu Asp Ile Phe Gly Ala 180 185 190 Ile Thr Ser Thr Ala Gly Ile Ala Ala Val Leu Tyr Ala Ile Val Arg 195 200 205 Ser Ala Asp Tyr Ser Trp Thr Asp Pro Phe Val Leu Ile Ser Leu Val 210 215 220 Leu Gly Ile Ala Val Phe Ile Trp Phe Leu Arq His Glu Ser Ser Ala 225 230 235 240 Lys Giu Pro Leu Leu Pro Leu Gly Leu Phe Lys Asn Arg Arg Arg Asn 245 250 255 Thr Ile Leu Ala Ser Arg Phe Leu Leu Val Gly Ser Val Met Ser Phe 260 265 270 Phe Phe Phe Al1a Thr Gin Leu Phe Gin Asp Thr Met Gly Met Asn Ala 275 280 285 Leu Gin Ala Gly Leu Ala Phe Met Pro Leu Ser Leu Leu Gin Phe Ala 290 295 300 Ser Ala Ala Met Val Pro Arg Leu Ser Arg Ala Gly Val Ser Asp Ser 305 310 315 320 Met Leu Thr Val Ile Gly Phe Ala Ilie Met Val Ile Gly Met Ala Gly 325 330 335 Leu Ala Phe Val Pro Asn Thr Met Ilie Ala Leu Ile Leu Pro Ile Val 340 345 350 Leu Val Gly Phe Gly Gin Gly Phe Ala Phe Gly Pro Met Thr Ala.Leu 355 360 365 Ala Val Gin Gly Ala Pro Lys Asp Gin Ser Gly Ala Val Ser Gly Leu WO 01/00804 370 375 Vai Asn Ser Leu His Gin Ile Gly Gly Thr Phe 385 390 395 Ser Ser Leu Ala Val Ala Val Ile Giy His Asp 405 410 Ile Ser Asp Arg Ala His Phe Gly Phe Leu Leu 420 425 Thr Leu Ala Thr Ile Phe Ala Val Thr Leu Leu 435 440 Arg Lys Ser Ser Glu Arg Pro Thr Gin Leu Val 450 455 Thr Ser 465 <210> 237 <211> 1584 <212> DNA <213> Corynebacterium giutamicum <220> <221> CDS <222> (1561) <223> RXA00215 <400> 237 cagtgcaaac tgaceccgca tcctaaaccg cgccagattt ccttttccag gcgccetcgt gcgtgaaaga ataactcaac PCTIBOO/00922 380 Giy Leu Gly Val Phe 400 Ala Thr Ser Glu Met 415 Ser Thr Val Thr Leu 430 Lys Arg His Giu Thr 445 Asp Giu Lys Ala Val 460 cag Gin gc Al a at t Ile gtg Val1 aac Asn cta aca Leu Thr ccc gct Pro Ala ttg tgc Leu Cys gte tet Val Ser gtc atc Val Ile tee Ser ccc Pro ggg Gly ca Pro gt a ValI 75 gca Ala t tg Leu ttt Phe gcg Al a ace Thr gca Ala ect Pro ttc Phe 45 tta Leu t cg Ser agt Sc r aag Lys ate Ile gca Al a tat Tyr etacctcaaa gaattgaagg gtg tct gac aaa aag Val Ser Asp Lys Lys 1 gca ccc caa. act aag Ala Pro Gin Thr Lys get tgg tea get eta Ala Trp Pro Ala Leu ttg gat caa ace ate Leu Asp Gin Thr Ile atg .ggc gcg tee tae Met Gly Ala Ser Tyr etc act ttc gcg gtg Leu Thr Phe Ala Val 115 163 211 259 307 355 WO 01/00804 WO 0100804PCT/IBOO/00922 eca ctg ctt gtt act ggc cgt ttg ggc gac aag Pro Leu Leu Val Thr Gly Arg Leu Gly Asp Lys 95 gtc tat gtc gca ggc atg git atc ttc aca gtg Val Tyr Val Ala Gly Met Val Ile Phe Thr Val 105 110 ggt ttg gcc eca gac atg ttc acg ttg att atc Gly Leu Ala Pro Asp Met Phe Thr Leu Ilie Ile 120 125 ggt ttg ggc gca gec ctt ttg act cca caa ac Gly Leu Gly Ala Ala Leu Leu Thr Pro Gin Thr 135 140 cgc atc ttt get ttt gag cgc egc ggt gca gct Arg Ile Phe Ala Phe Giu Arg Arg Gly Ala Ala 150 155 160 tct aca get ggc ctt gca tee cta gea gga ccg Ser Thr Ala Gly Leu Ala Ser Leu Ala Gly Pro 170 175 ate ace gaa aae tgg ggt tgg caa tgg gte ttc Ile Thr Giu Asn Trp Gly Trp Gin Trp Vai Phe 185 190 atc ggc gtg ate teg gtg atc gca gta atg aag Ilie Gly Val Ilie Ser Val Ile Ala Val Met Lys 200 205 eca ccg ctg acc cga ccg ctt gat ceg ett tct Pro Pro Leu Thr Arg Pro Leu Asp Pro Leu Ser 215 220 gtg gcc gtg ttc ttc etg gtg ttt gct ttc cag Val Ala Val Phe Phe Leu Val Phe Ala Phe Gin 230 235 240 ggc tgg gcg gca tgg gtg tgg atc atg ate gta Giy Trp Ala Aia Trp Val Trp Ile Met Ile Val 250 255 ttt geg tgg ttt atc tac caa eaa age agg gee Phe Ala Trp, Phe Ile Tyr Gin Gin Ser Arg Ala 265 270 gat ect etc gte eea etg gag att tte aag ttt Asp Pro Leu Val Pro Leu Glu Ile Phe Lys Phe 280 285 tae ggt ceg aaa aat Tyr Gly Pro Lys Asn 100 ag Se, get Ala a tc Met 145 ctt Leu at c Ile tac Tyr t ae Tyr ate Ile 225 gaa Giu gee Ala gag Glu a ga krg :tet :Ser egt Arg 130 gca Ala *gga I Gly ctg *Leu ate Ile gtt Val 210 gtg Val gge Gi y gee Ala aaa Lys aae As n 290 ttg Leu 115 gge Gi y aca Th r gtg Val ggt Gly aae Asn 195 ct Pro ttg Leu gaa Glu ttt Phe tee Ser 275 tte Phe gee Ala gtt Val ate Ile tgg T rp ggt Gi y 180 gt g Val1 gaa Giu tee Ser ggc Gly geg Al a 260 gga Gl y age Ser tqt Cys caa Gin aac Asn gg t Gi y 165 gte Val ccc Pro tte Phe ate Ile get Al a 245 etc Leu aae Asn ct e Leu 403 451 499 547 595 643 691 739 787 835 883 931 979 1027 gge aat Gly Asn 295 ate tge ate atg Ile Cys Ile Met gee Ala 300 atg gga ttc ace Met Gly Phe Thr gtg Val1 305 gct ggt act eet Ala Gly Thr Pro WO 01/00804 WO 0100804PCTIIBOO/00922 ctg ccc atc Leu Pro Ile atg ttg Met Leu tac ttc cag caa gca cac gga Phe Gin Gin Ala His Giy atg aac gcc atg Met Asn Ala Met 310 gaa Giu t ca Ser qca Ala atg Met act Thr 390 t cc Se r gtg Vali atc Ile gct Ala att gcg ggt Ala Giy cca ttt Pro Phe gcC ctc Ala Leu 360 gta atg Val Met 375 ttg ctc Leu Leu act atg Thr Met ttc aat Phe Asn ggc gcg Gly Ala 440 ttt ggt Phe Gly 455 gtg gca ttc Phe gt t Val1 345 ggt Gi y att Ile Gi y cgc Arg aca Th r 425 gt a Val1 caa Gin tca atg, Met 330 gga Gi y ttt Phe ttc Phe atc Ile gac Asp 410 acc Thr a tg Met gca Ala acg Tyr 315 atg Met aag Lys a gc S er gat Asp gga Gly 395 ctg Leu cgc Arg cag Gin ct t Leu at g gtg Val ctg Leu aca Thr acg Thr 380 aac Asn cca Pro caa Gin att Ile ct a Leu 460 gca cct Pro gt t Val1 gt g Val1 365 ggt Gly gcc Ala cac His tta Le u cga Arg 445 ctt Leu gga Gly caa Gin gat Asp 350 gct Ala cta Leu ttt Phe aag Lys ggt Gly 430 ct g Leu gcc Ala 320 gct ctc Ala Leu 335 cga tc Arg Ser gtg tcC Val Ser gtC tgg Val Trp gtq tgg Val Trp 400 ttc atg Phe Met 415 tca gtc Ser Val gca gca Ala Aia gct gcg Ala Ala atg Met aac As n att Ile gca Ala 385 gca Ala gga Gly atc Ile.
Gi y gtg Val 465 gca Ala gga Gly 355 ct g Leu gt t Val1 aac Asn ggc Gi y gcc Ala 435 gag Giu gt t Val1 325 ctg Leu atg Met t ca Ser atg Met acc Thr 405 ggc Gly gcc Al a gca Al a ggC Gi y 1075 1123 1171 1219 1267 1315 1363 1411 1459 1507 1555 1584 aaa aat gca cac cca gcg ccg gta Lys Asn Ala His Pro Ala Pro Val Ile Val Ala Ser Thr Met Ala aag cct Lys Pro taaaggtcgc atgaatcctt cga <210> 238 <211> 487 <212> PRT <213> Corynebacterium giutamicun <400> 238 Val Ser Asp Lys Lys Gin Asp Leu Thr Ser Ser Ala Ala Gly Ser Ala 1 5 10 wo 01/00804 WO 0100804PCT/IBOO/00922 Ala Pro Gin Thr Lys Ala Tyr Pro Ala Met Pro Leu Pro Glu Lys Gin Ala Trp Leu Asp Met Gly Leu Thr Tyr Gly Ser Ser Ala Arg 130 Met Ala 145 Leu Gly Ile Leu Tyr Ile Tyr Val 210 Ile Val 225 Giu Gly Ala Ala Giu Lys Arg Asn 290 Val Ala 305 Al a Thr Ser Ala Lys 100 Ala Val1 Ile Trp Gly 180 Val1 Gl u Se r Gi y Ala 260 Giy Ser Thr 25 Leu Ile Tyr Val Asn Cys Gin Asn Gly 165 ValI Pro Phe Ile Ala 245 Leu Asn Leu Pro Sle Val1 Asn 70 Pro Val1 Gly Gi y Arg 150 Se r Ile Ile Pro Val1 230 Gly Phe Asp Gly Leu 310 Ala Ala Giu Leu Tyr Leu Leu 135 Ile Th r Thr Gly Pro 215 Ala Trp Al a Pro Asn 295 Pro Leu Val Val1 Leu ValI Al a 120 Gly Phe Ala Giu Val 200 Leu Val1 Al a Trp Leu 280 Ilie Ile Cys Se r Ilie Val1 Ala 105 Pro Ala Al a Gly Asn 185 Ilie Thr Phe Al a Phe 265 Val Cys M2et Ile Thr Trp Thr 90 Gly Asp Ala Phe Le u 170 Trp Ser Axg Phe Trp 250 Ile Pro Ie Leu Gly Pro Val 75 Gly Met Met Leu Glu 155 Ala Gly Val1 Pro Leu 235 Val1 Tyr Leu Met Tyr 315 Phe Leu Ser Leu Ile Thr 125 Thr Arg Leu Gin Al a 205 Asp Phe Ile Gin Ile 285 Met Gin Met Gin Val1 Gly Phe 110 Leu Pro Gi y Al a T rp 190 Val1 Pro Al a Met Ser 270 Phe Giy Gin Ilie Leu Ala Asp Tyr Leu Asp Lys Thr Val Ile Ile Gin Thr Ala Ala 160 Gly Pro 175 Val Phe Met Lys Leu Ser Phe Gin 240 Ile Val 255 Arg Ala Lys Phe Phe Thr Ala His 320 Gi y Met Asn Ile Ala 385 Ala Gly Ile Gly Val1 465 His WO 01/00804 Met Asn Ala Met 325 Ala Ala Val Leu 340 Pro Gly Leu Met 355 Val Leu Leu Ser 370 Leu Val Ser Met Pro Asn Ser Thr 405 Ala Gly Ser Gly 420 Gly Ala Ala Ala 435 Asp Glu Gly Ala 450 Leu Val Ile Gly Pro Ala Pro Val 485 Giu Se r Al a Met Thr 390 Ser Val1 Ile Ala Ile 470 Lys Ala Pro Ala Val1 375 Leu Thr Phe Gi y Phe 455 Val1 Pro Met Lys Ser Asp Gl y 395 Leu Arg Gin Leu Met 475 Val Leu Thr Th r 380 As n Pro Gin Ile Leu 460 Ala Pro Val1 Vali 365 Gly Ala His Leu Arg 445 Leu Gly PCT/IBOO/00922 Gin Ala 335 Asp Arg 350 Ala Val Leu Val Phe Val Lys Phe 415 Gly Ser 430 Leu Ala Ala Ala Lys Asn <210> 239 <211> 1455 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> (1432) <223> RXN03064 <400> 239 tggagccttg tcttcctcca gcaatcccac aacggagcag gttgggatcc cgagaaatgt tgtcatcatc ttggctgtat tagtttttac agcctttgtc atg atg ttg aat gag Met Met Leu Asn Giu 1 act act ctg gca gtc gcg ttg ccg tcq atc atg gcg gac ttt gac att Thr Thr Leu Ala Val Ala Leu Pro Ser Ile Met Ala Asp Phe Asp Ile 15 gag gcq aat act gcg cag tgg ttg ctc act ggt ttt atg ttg acc atg WO 01/00804 WO 0100804PCT/IBOO/00922 Glu Ala Asn Thr Ala Gin Trp Leu Leu Thr Gly Phe Met Leu Thr Met 30 gct Ala cgt Arg acg Th r gct Ala gcg Ala att Ile ggt Gly gtt ValI 150 aac As n att Ile Gly 9gc Gly aag Lys 230 gtg Val1 ag t Se r gct Al a cag Gin atg Met gcg Ala ttC Phe 135 ccg Pro gt C Val tcc Ser atc Ile atc Ile 215 cag Gin gtt Val1 g tg Val1 gcg Ala gcg Ala acc Thr gt C Val1 120 gt a Val1 t tg Leu agt Ser gca Ala att Ile 200 att Ile ga t Asp ctt Leu ttt Phe t tg Leu att I le gt t Val1 105 gt g Val1 Ct C Leu gtg Val gag Glu gtg Val 185 ttg Leu gcg Al a aag Lys cca PrC att Ile tct Ser gg t Gi y gt t Val1 atg Met agc Ser tt Phe cct Pro 170 gct Al a gaa Glu ttg Leu gcg Ala gCt Ala ttc Phe *cct *Pro 75 acc Thr cct Pro gcc Al a ttg Leu gtg Val1 155 aaa Lys ttc Phe ggt Gly gtg Val ctg Leu 235 act Thr gcc Al a 60 act Th r gCt Al a cca Pro qt t Val t ct Ser 140 gca Al a aag Lys ggt Gly gac Asp gtg Val1 220 Ltg Leu ggt Gly 45 acg Thr ttt Phe gtg ValI gag Glu ggt Gly 125 t cg Ser' a gc Ser act Thr ggc Gly aga Arg 205 ttt Phe gat Asp t gg Trp gtg Val1 gcg Ala atc Ile cgc Arg 110 CCt Pro t gg T rp ctg Leu cct Pro ct t Leu 190 agc Ser gtg Vai ctg Leu atg Met gt C Val1 att Ile a tg Met 95 cgt Arq gct Ala cac His atc Ile ttg Le u 175 gtg Val gct Ala tgq Trp, cg t Arg ttg Leu ttc Phe a tg Met 80 ccg Pro ggc Gly ctt Leu gcg Al a ggt Gly 160 gat Asp tac Tyr t tg Leu cgc Arg ccg Pro 240 gaa Giu ctg Leu ctt Leu ctg Leu gcc Ala gga GI y att Ile 145 acc Thr gtt Vai gcc Ala gtc Val cag Gln 225 ttg Leu cgt Arg atc Ile gca Ala ctg Leu gt c Val1 cct Pro 130 ttc Phe ctg Leu att Ile ttg Leu gtg Val1 210 at t I le gcg Al a ttt Phe ggt Gi y gcc Ala atg Met atg Met 115 agt Ser t gg T rp cgt Arg tcc Ser agc Se r 195 ttg Leu gcc Al a att Ile acc act Thr Thr act gtg Thr Val cgc gtC Arg Val act gtc Thr Val 100 ggt ttg Gly Leu gtg gct Val Ala gtc atg Val Met ctg acc Leu Thr 165 ttc ctg Phe Leu 180 tcg att Ser Ile gCt gtc Aia Val atq ggt Met Gly cgt gag Arg Glu 245 259 307 355 403 451 499 547 595 643 691 739 787 835 tac acc att ccg ctg gtt gtg ctt ttg Tyr Thr Ile Pro Leu Val Val Leu Leu acg ctg ttc Thr Leu Phe ggt gcg ctg ctc Gly Ala Leu Leu WO 01/00804 WO 0100804PCTIIBOO/00922 9gt Gly acc Thr ggt Gi y cgc Arg 310 gca Ala gta Val1 a tg Met t cc Ser gcg Ala 390 ga c Asp ttc Phe gtc Val1 gCC Al a gt g Val1 295 gga Gly ctg Leu cac His aca Thr gCg Al a 375 gt C Val1 ggc Gly ttc Phe atg Met ttg Le u 280 ct g Leu ctc Leu t~c Ser atc Ile gt c Val1 360 at c Ile atg Met gca Ala gcC Ala aat Asn 265 gt C ValI t cg Ser gt q Val1 acc Thr gtg Val 345 gcg Ala ctc Leu att Ile acc Tb r t ca Se r 425 250 8 C8 Thr gcg Ala cca Pro atc Ile gt c ValI 330 ttc Phe ctc Leu aac Asn qcg Ala caa Gin 410 gcg Ala ct g Leu ggt Gi y ttt Phe ggc Gly 315 gat Asp tcC Se r gca Al a acc Thr gt t Val 395 caa Gin tgC ccg Pro ct a Leu gtg Val 300 ggt Gly gag Si u at c Ile tcc Ser ctc Leu 380 tat Tyr acc Tb r gt g ctc Leu gtg Val 285 ggt Giy atg Met tt C Phe ggC Gly gtc Val 365 caa Gin tcC Se r gcc Ala gca tac Tyr 270 ctg Leu cga Arg tca Ser gcc Ala .ctt Leu 350
CCC
Pro cag Gin acc Thr ctc Leu gtg 255 Ctg Leu ttg Leu att.
Ile Ctc Leu aac As n 335 gcg Ala gac Asp ctc Leu gt c Val gcc Ala 415 tt cag Gin cca Pro tat Tyr gtt Val 320 gtg Val1 ctg Leu aac Asn gc Ala a gc Ser 400 gac Asp gca gga Gly ggt Gi y ga t Asp 305 gt g Val1 tgg Trp ctg Leu atg Met ggC Gly 385 aac As n ggc Gi y Ctg tcc Ser ggt Gly 290 cgt Arg atc Ile ttc Phe ttc Phe tac Tyr 370 gcc Al a aac Asn gcc Ala atc t tg Leu 275 ct t Leu cat His tcc Ser atc Ile aCC Thr 355 ggC Sly gca Al a gcg Ala aac Asn gtg Val1 435 260 atg gtc Met Val ttg gaa Leu Giu ggt cca Sly Pro ctg ttt Leu Phe 325 atc ggc Ile Gly 340 cca ctg Pro Leu cac ggc His Gly ggc acc Sly Thr ctt atc Leu Ile 405 tct gca Ser Ala 420 ggc ttC Sly Phe 931 979 1027 1075 1123 1171 1219 1267 1315 1363 1411 1455 Val Ala Val Phe Ala Leu Ile ttt gta Phe Val aag agg cca Lys Arg Pro 440 gcc cgc taagctaggt cgcatgatca gca Ala Arg <210> 240 <211> 444 <212> PRT <213> Corynebacterium giutamicwn <400> 240 WO 01/00804 WO 0100804PCT/IBOO/00922 Met Met Leu Asn Giu Thr Thr Leu Ala Val Ala Leu Pro Ser Ile Met Ala Phe Giu Leu Leu Leu Ala Gly Ile 145 Thr Val1 Ala Val Gin 225 Leu Phe Gly Asp Phe Met Leu Arg Phe Ilie Gly Ala Ala Leu Met Val Met Pro Ser 130 Phe Trp Leu Arg Ile Ser Leu Ser 195 Vai Leu 210 Ile Ala Ala Ile Gly Ala Ser Leu 275 Asp Ile Thr Met Thr Thr Thr Vai Arg Val Thr Val 100 Giy Leu Val Ala Val Met Leu Thr 165 Phe Leu 180 Ser Ilie Ala Val Met Gly Arg Glu 245 Leu Leu 260 Met Val Giu Al a Arg Th r 70 Al a Ala Ile Gly Val1 150 Asn Ile Gly Gly Lys 230 Tyr Gly Thr Al a Val Ser 55 Ala Gin Met Ala Phe 135 Pro Val1 Se r Ile Ile 215 Gin Thr Val Ala Asn Val 40 Val Ala Al a Thr Val1 120 Val Leu Sc r Al a Ile 200 Ilie Asp Ile Met Leu 280 Thr 25 Leu Phe Leu Ile Val1 105 ValI Leu Val Giu Val 185 Leu Ala Lys Pro Asn 265 Val1 Ala Gin Trp Pro Ala Thr Ile Phe Ala Ser Pro Thr 75 Gly Thr Ala 90 Val Pro Pro Met Ala Val Ser Leu Ser 140 Phe Val Ala 155 Pro Lys Lys 170 Ala Phe Gly Glu Gly Asp Leu Val Val 220 Ala Leu Leu 235 Leu Val Val 250 Thr Leu Pro Ala Gly Leu Leu Leu Thr Gly Gly Trp Met Leu Thr Val Val Phe Phe Ala Ile Met Val Ile Met Pro Giu Arg Arg Gly 110 Gly Pro Ala Leu 125 Ser Trp His Ala Ser Leu Ile Gly 160 Thr Pro Leu Asp 175 Gly Leu Val Tyr 190 Arg Ser Ala Leu 205 Phe Val Trp Arg Asp Leu Arg Pro 240 Leu Leu Thr Leu 255 Leu Tyr Leu Gin 270 Val Leu Leu Pro 285 Gly Gly 290 Leu Leu Giu Gly Val Leu Ser Pro Phe Val Gly Arg Ile Tyr WO 01/00804 Arg His Gly Pro Ile Ser Leu Phe 325 Phe Ile Ilie Gly 340 Phe Thr Pro Leu 355 Tyr Gly His Gly 370 Ala Ala Gly Thr Asn Ala Leu Ile 405 Ala Asn Ser Ala 420 Ile Val Gly Phe 435 PCT/IBOO/00922 Leu Ser Ile Val1 360 Ile Met Al a Ala Lys 440 <210> 241 <211> 1093 <212> DNA <213> Corynebacterium giutamicum <220> <221> CDS <222> (101)..(1093) <223> FRXA00565 <400> 241 tggagccttg tcttcctcca. gcaatcccac aacggagcag tgtcatcatc ttggctgtat tagtttttac agcctttgtc act act ctg gca gtc gcg ttg ccg tcg atc atg Thr Thr Leu Ala Val Ala Leu Pro Ser Ile Met 15 gag gcg aat act gcg cag tgg ttg ctc act ggt Glu Ala Asn Thr Ala Gin Trp Leu Leu Thr Gly 30 gct gtg gtt ctt cca gct act ggt tgg atg ttg Ala Val Val Leu Pro Ala Thr Gly Trp Met Leu 45 gttgggatcc cgagaaatgt atg atg ttg aat gag Met Met Leu Asn Giu 1 gcg gac ttt gac att Ala Asp Phe Asp Ile ttt atg ttg acc atg Phe Met Leu Thr Met gaa. cgt ttt acc act Glu Arg Phe Thr Thr WO 01/00804 WO 0100804PCT/IBOO/00922 eg t Arg acg Thr get Ala 9gg Ala att Ile ggt Gly gtt Val1 150 aac As n at t Ile Gly ggc Gly aag Lys 230 tac Tyr ggt Gly agt gtg Ser Val get gcg Ala Ala ttt att ttc gcc acg gtg gtc ttc etg ate ggt act gtg Gly Thr Val geg Al a ace Thr gt c Val1 120 gt a Val ttg Leu agt Ser gca Ala att Ile 200 att Ile gat Asp att Ile atg Met Phe ttg Leu att I le gt t Val 105 gtg ValI Cc Leu gtg Val gag Glu gt g Val1 185 ttg Leu gcg Ala a ag Lys ceg Pro aat Asn Ile t et Ser gg t Gly 90 gt t Val1 atg Met agc Ser ttt Phe cot Pro 170 get Ala gaa Glu t tg Leu geg Ala ctg Leu 250 aca Th r 60 cct Pro 75 ace Thr ct Pro gee Ala ttg Leu gtg ValI 155 aaa Lys ttC Phe ggt Gly gtg Val1 ctg Leu 235 gt t Val1 ctg Leu act Thr get Al a cca Pro gt t Val1 tet Se r 140 gca Al a aag Lys ggt Gly gac Asp gtg Val 220 ttg Leu gt g ValI ceg Pro ttt Phe gtg Val1 gag Glu ggt Gly 125 t cg Ser agc Ser act Thr gge di y aga Arg 205 ttt Phe gat Asp ct t Leu etc Leu qgg Ala atc Ile ege Arg 110 cct Pro tgg Trp et g Leu cct Pro ct t Leu 190 age Ser gtg Val1 ctg Leu ttg Leu tac Tyr 270 att Ile a tg Met cg t Arg gct Al a eac His ate Ile ttg Leu 175 gtg ValI get Al a t gg Trp cgt Arg acg Thr 255 ctg Leu atg ett Met Leu ccg etg Pro Leu gge gcc Gly Ala ett gga Leu Gly geg att Ala Ile 145 ggt ace Gly Thr 160 gat gtt Asp Val tac gee Tyr Ala ttg gte Leu Val ege eag Arg Gin 225 ceg ttg Pro Leu 240 ctg tte Leu Phe eag gga Gin Glv Phe Ala Thr Val Val Phe Leu Ile 307 355 403 451 499 547 595 643 691 739 787 835 883 931 265 275 acc gee ttg gte geg ggt eta gtg etg ttg eca ggt ggt ctt ttg gaa WO 01/00804 Thr Ala Leu Val 280 ggt gig ctg tcg Gly Val Leu Ser 295 cgc gga etc gtg Arg Gly Leu Val 310 gca ctg tcc acc Ala Leu Ser Thr PCT/IBOO/00922 Gly Leu Val Leu Leu Pro Gly Gly Leu Leu Giu 285 290 ttt gtg ggt cga att tat gat cgt cat ggt cca Phe Val Gly Arg Ile Tyr Asp Arq His Gly Pro 300 305 ggc ggt atg tca ctc qtt gtg atc tcc ctg ttt Gly Gly Met Ser Leu Val Val Ile Ser Leu Phe 315 320 325 gat Asp 1027 1075 1093 <210> 242 <211> 331 <212> PRT <213> Corynebacterium giutamicum <400> 242 Met Met Leu Asn Glu Thr Thr Leu Ala Val Ala Leu Pro Ser Ile Met 1 Ala Asp Phe Met Giu Arg Leu Ile Leu Ala Leu Leu Ala Val Gly Pro 130 Ile Phe 145 Thr Leu Phe Leu Phe Gly Ala Met Met 115 Ser Trp Arg Asp Thr Thr Th r Arg Thr 100 Gly Val Val1 Leu 5 Ile Met Thr Val Val Val Leu Al a Met Thr Giu Ala Arg Thr 70 Ala Al a Ile Gly Val1 150 Asn Al a Val1 Se r 55 Al a Gin Met Ala Phe 135 Pro Val1 Asn Val 40 Val1 Al a Ala Thr Val1 120 Val1 Lcu S er Thr 25 Leu Phe Leu Ile Val1 105 Val Leu Val1 Glu 10 Ala Pro Ile Ser Giy 90 Val1 Met Ser Phe Pro 170 Gin Ala Phe Pro 75 Thr Pro Ala Leu Val 155 Lys Trp Thr Al a Thr Al a Pro ValI Ser 140 Ala Lys Leu Gly Thr Phe ValI Glu Gly 125 Ser Ser Thr Leu Trp Val Ala I le Arg 110 Pro Trp Leu Pro Thr Gly Met Leu Val Phe Ile Met Met Pro Arg Gly Ala Leu His Ala Ile Gly 160 Leu Asp 175 Val Ile Ser Phe Leu Ile Ser Ala Val Ala Phe Gly Gly Leu Val Tyr WO 01/00804 PCT/IBOO/00922 Ala Leu Ser Ser Ile Gly Ile Ile Leu Glu Gly Asp Arg Ser Ala Leu 195 200 205 Val Val Leu Ala Val Gly Ile Ile Ala Leu Val Val Phe Val Trp Arg 210 215 220 Gin Ile Ala Met Gly Lys Gin Asp Lys Ala Leu Leu Asp Leu Arg Pro 225 230 235 240 Leu Ala Ile Arg Glu Tyr Thr Ile Pro Leu Val Val Leu Leu Thr Leu 245 250 255 Phe Gly Ala Leu Leu Gly Val Met Asn Thr Leu Pro Leu Tyr Leu Gin 260 265 270 Gly Ser Leu Met Val Thr Ala Leu Val Ala Gly Leu Val Leu Leu Pro 275 280 285 Gly Gly Leu Leu Glu Gly Val Leu Ser Pro Phe Val Gly Arg Ile Tyr 290 295 300 Asp Arg His Gly Pro Arg Gly Leu Val Ilie Gly Gly Met Ser-Leu Vai 305 310 315 320 Val Ile Ser Leu Phe Ala Leu Ser Thr Val Asp 325 330 <210> 243 <211> 380 <212> DNA <213> Corynebacterium glutamicun <220> <221> CDS <222> <223> FRXA02878 <400> 243 tgc cig tcc acc gtc gat gag ttc gcc acg tgt tgq tca tca tic gCg 48 Cys Leu Ser Thr Val Asp Giu Phe Ala Thr Cys Trp Ser Ser Phe Ala 1 5 10 gac aca tcg tgg tic tca tcg gcc cit gcg ctg cig ttc acc cca ctg 96 Asp Thr Ser Trp Phe Ser Ser Ala Leu Ala Leu Leu Phe Thr Pro Leu 25 atg aca gtc gcg ctc gca icc gtc ccc gac aac atg tac ggc cac ggc 144 Met Thr Val Ala Leu Ala Ser Val Pro Asp Asn Met Tyr Gly His Gly 40 icc gcg atc cic aac acc ctc caa cag cic gcc ggc gcc gca. ggc acc 192 Ser Ala Ile Leu Asn Thr Leu Gin Gin Leu Ala Gly Ala Ala Gly Thr 55 gcg gtc atg ati gcg git tat icc acc gtc agc aac aac gcg cit atc 240 WO 01/00804 Ala Val Met Ile gac gqc qca aCC Asp Gly Ala Thr ttc ttc gcc tca Phe Phe Ala Ser 100 ttt gta aag agg Phe Val Lys Arg 115 PCT/IBOO/00922 Ser Thr Val Ser Asn Asn Ala Leu Ile 75 gcc ctc gec gac ggc gcc aac tct gca Ala Leu Ala Asp Gly Ala Asn Ser Ala gca gtg ttt gca ctg atc gtg ggc ttc Ala Val Phe Ala Leu Ile Val Gly Phe 105 110 taagctaggt cgcatgatca gca <210> 244 <211> 119 <212> PRT <213> Corynebacterium glutamicum <400> 244 Cys Leu Ser Thr Vail Asp Giu PheAla 1 5 Asp Thr Ser Trp Phe Ser Ser Ala Leu 25 Met Thr Val Ala Leu Ala Ser Val Pro Ser Ala Ile Leu Asn Thr Leu Gin Gin 55 Ala Vai Met Ile Ala Val Tyr Ser Thr 70 Asp Gly Ala Thr Gin Gin Thr Ala Leu Phe Phe Ala Ser Ala Cys Val Ala Val 100 105 Phe Val Lys Arg Pro Ala Arg 115 <210> 245 <211> 1533 <212> DNA <213> Corynebacterium giutamicum <220> <221> CDS <222> (1510) <223> RXA00648 Thr Cys 10 Ala Leu Asp Asn Leu Ala Val Ser Ala Asp 90 Phe Ala Trp Leu Met Gly Asn Gly Leu Se r Thr Giy Ala Ala As n Val1 110 Phe Pro His Gly Le u Se r Cly WO 01/00804 <400> 245 gtttgccagc tattgcatct tgcacaaaat gtgiaccata PCTIBOO/00922 cacataatgt catcgagtcc tcccgaatca gccacaccac agatcaaata cggcctgctg tca Set att Ilie t gg Trp atg Met tca Set gat Asp ggC Gi y gag Glu ggc Giy Ser 150 9gc Gly agt gct Al a ggi Gly atc Ile Gly ct t Leu tg Leu ct g Leu aaa Lys ggt Gly 135 tgg Trp gcg Al a gg t Gi y Arg at Ile agg Arg gt C Val1 ati Ile att Ile gca Ala 120 gca Al a c9g Arg gtc Va 1 *atc Ile tg Leu act Thr ct Leu ccg Pro ccg Pro cct Pro 105 ggg Gly ci c Le u gtg Val att le tt C act Thi ccc Pro gig Val1 gca Al a tic Phe atg Met ctt Leu tct Ser ggi Gly ct g Leu t gg FTp, 170 ;at gtt tcc cta gcg Val Ser Leu Ala gag Glu acg Thr ga t Asp at Ile 75 atc Ile Gly gcc Ala cia Leu ttc Phe 155 aag Lys tatI atc I le ctg Leu atg Met 60 ct Leu atc Ile at Ile at I le ccg Pro 140 tgg rrp ;cg !U a ttc tic Phe tig ILeu 45 tac Tyr gga Gly Gly tci Ser gci Al a 125 cig Leu tic Phe ati Ile qgt Gly aac Asn 30 gig ValI Gly tca Set cgi Arg cic Leu 110 ttg Leu gci Ala acc Thr Pro gct kla 190 cag Gin 15 acc Thr ggc Gly aag Lys gig Val ggi Gl y 95 atg Met atg Met gct Ala gCt Ala gci Ala 175 ctc Leu acc Thr a cg Thr gca Ala aaa Lys atc Ile 80 ttt Phe cat His a gt S er gci Ala cig Leu 160 aga Arg 9gc Gly gig Val 1 ctg Leu gct Ala gtg Val aag Lys 65 ige Cys cag Gin gati Asp ici Ser at Ile 145 gi a Val1 ccc Pro ct t Leu gt i Val1 gc t Ala gcg Ala 50 atg Met gci Ala ggg Gly tig Leu icc Ser 130 gcc Al a gcg Ala agg Arg gca Ala at i Ile aai Asn 35 act Thr aig Met gig Val ct i Leu to Leu 115 atg Met cag Gin cti Leu aic I le atg Met 195 gic act cic gcc Val Thr Leu Ala ccg Pro 20 gcC Ala cct Pro ct c Leu i cg Ser Gl y 100 ccc Pro ggc Sly ttt Phe aca Thr gig Val1 180 gga Gi y aic Ile tct Set gig ValI aic Ile gig Val ici Set Arg at Ile gcg Al a gtt ValI 165 a gg Arg cii Leu 115 163 211 259 307 355 403 451 499 547 595 643 691 Set Sly Gly Phe Asp Tyr Phe 185 atc gca Ile Ala t 0 tig cic gcg gig icc aag Leu Leu Leu Ala Val Set Lys gga Gly ica gaa tgg Set Glu Ttp ggc tgg aga Gly Trp Arq WO 01/00804 PCTIIBOO/00922 200 205 210 agt gce ctg acc att ggg tta ttc gtg gca gcg ctg gtg att ttg gtg 787 Ser Ala Leu Thr Ile Gly Leu Phe Val Ala Ala Leu Val Ile Leu Val 215 220 225 ggt tgg gge tgg ttc gaa acc cgc cag aaa tcc ect ttg att gat etg 835 Gly Trp Gly Trp Phe Giu Thr Arq Gin Lys Ser Pro Leu Ile Asp Leu 230 235 240 245 egc act act att egg gcg aec gtg ttg atg aca aat att gcg tee atc 883 Arg Thr Thr Ile Arg Ala Thr Val Leu Met Thr Asn Ile Ala Ser Ile 250 255 260 etc ate ggt tte ace atg tat gga atg aat etg atc ctg cet eag gte 931 Leu Ile Gly Phe Thr Met Tyr Gly Met Asn Leu Ile Leu Pro Gin Val 265 270 275 atg cag ctg cct gta att etg ggc tac ggt eta ggc cag agc atg ctt 979 Met Gin Leu Pro Val Ile Leu Gly Tyr Gly Leu Giy Gin Ser Met Leu 280. 285 290 cag atg ggc atc tgg ctg atc ceg atg ggt cta gge atg atg ttg att. 1027 Gin Met Gly Ilie Trp Leu Ile Pro Met Giy Leu Gly Met Met Leu Ile 295 300 305 teg aat gea ggt gea gee att age get get cat ggt cet egt gtg aeg 1075 Ser Asn Ala Gly Ala Ala Ile Ser Aia Ala His Gly Pro Arg Vai Thr 310 315 320 325 etg aea att geg ggt gtt gtg ate gca gte ggt tat gea ett act gee 1123 Leu Thr Ile Ala Gly Val Val Ile Ala Val Gly Tyr Ala Leu Thr Ala 330 335 340 aca gtg ttg tte act ate ggc aae ege aea ceg gga gga gat gea gac 1171 Thr Val Leu Phe Thr Ile Giy Asn Arg Thr Pro Gly Gly Asp Ala Asp 345 350 355 aae gea ett att ttg ace ace etg gtg etg tte tea gtg tgt agt etc 1219 Asn Ala Leu Ile Leu Thr Thr Leu Vai Leu Phe Ser Val Cys Ser Leu 360 365 370 gtg gte ggt ate gge att gge ctg gea ttt ggt tee atg eet gee ttg 1267 Val Val Gly Ilie Gly Ile Gly Leu Ala Phe Giy Ser Met Pro Ala Leu 375 380 385 ate atg ggt gee gta eta gee aeg gag aaa gee gca geg aat ggt tte 1315 Ile Met Gly Ala Val Pro Ala Thr Giu Lys Ala Ala Ala Asn Gly Phe 390 395 400 405 aae tet ctt atg egt tea ctg ggc ace ace gge tea tea get gte ate 1363 Asn Ser Leu Met Arg Ser Leu Gly Thr Thr Gly Ser Ser Ala Val Ile 410 415 420 ggt gea gtg ttg gce gga atg atg agt ggc gga gta eec ace tta ggg 1411 Gly Ala Val Leu Ala Gly Met Met Ser Gly Gly Val Pro Thr Leu Gly 425 430 435 WO 01/00804 PCT/1BO0100922 gga ttc atg acc act ctg atc ate gga tgc: tgc gce gcg ctt gtg get 1459 Gly Phe Met Thr Thr Leu Ile Ile Gly Cys Cys Ala Ala Leu Val Ala 440 445 450 gcg gtc ate tcc tat ttc ate ccc ace aca. acc act gtq gtg gaa gca 1507 Ala Vai Ile Ser Tyr Phe Ile Pro Thr Thr Thr Thr Val Val Glu Ala 455 460 465 aaa taatcceggc agcgactcga cca. 1533 Lys 470 <210> 246 <211> 470 <212> PRT '213> Corynebacterium glutamicum <400> 246 Val Val Thr Leu Ala Ser Ala Gly Ile Thr Val Ser Leu Ala Gin Thr 1 Leu Ala Vai Lys Cys Gin Asp Ser Ile 145 Val Pro Val1 Ala Al a Met Al a Gi y Leu Ser 130 Al a Al a Arg Ile Asn Thr Met Val Leu Leu 115 Met Gin Leu Ile Pro Al a Pro Leu Se r Gi y 100 Pro Giy Phe Thr Val1 5 Ile Ser Val Ile Val1 Ser Arg Ile Ala Val1 165 Arg Ile Trp Met Ser 70 Asp Giy Glu GI y Se r 150 Gly Ser Gly Ile Gi y 55 Leu Leu Leu Lys Gly 135 Trp Ala Gly Arg I le 40 Arg Val Ile Ile Al a 120 Ala Arg Val1 Gly Leu 25 Thr Leu Pro Pro Pro 105 Gi y Leu Val1 Ile Phe 185 10 Pro Vai Ala Phe Met 90 Leu Ser Gly Leu Trp 170 Asp Gi u Th r Asp Ile Ile Giy Al a Leu Phe 155 Lys Tyr Ile Leu Met Leo Ile Ile Ile Pro 140 T rp Ala Phe Phe Asn Leo Val Tyr Gly Gly Ser Gly Arg Ser Leu 110 Ala Leu 125 Leu Ala Phe Thr Ile Pro Gly Ala Thr GI y Lys Val Gb y Met Met Al a Ala Al a 175 Leu 180 190 Leu Ala met Gly Le Ile Ala Leu Leu Leu Ala Val Ser Lys Gly Ser WO 01/00804 PCT/TBOO/00922 195 200 205 Glu Trp Gly Trp Arg Ser Ala Leu Thr Ile Gly Leu Phe Val Ala Ala 210 215 220 Leu Val Ile Leu Val Gly Trp Gly Trp Phe Giu Thr Arg Gin Lys Ser 225 230 235 240 Pro Leu Ilie Asp Leu Arq Thr Thr Ile Arq Ala Thr Val Leu Met Thr 245 250 255 Asn Ile Ala Ser Ile Leu Ile Gly Phe Thr Met Tyr Gly Met Asn Leu 260 265 270 Ile Leu Pro Gin Val Met Gin Leu Pro Val Ile Leu Gly Tyr Giy Leu 275 280 285 Gly Gin Ser Met Leu Gin Met Gly Ile Trp Leu Ile Pro Met Gly Leu 290 295 300 Gly Met Met Leu Ilie Ser Asn Ala Gly Ala Ala Ile Ser Ala Ala His 305 310 315 320 Gly Pro Arg Val Thr Leu Thr Ile Ala Gly Val Val Ile Ala Val Gly 325 330 335 Tyr Ala Leu Thr Ala Thr Val Leu Phe Thr Ile Gly Asn Arg Thr Pro 340 345 350 Gly Gly Asp Ala Asp Asn Ala Leu Ile Leu Thr Thr Leu Val Leu Phe 355 360 365 Ser Val Cys Ser Leu Vai Val Giy Ile Gly Ile Gly Leu Ala Phe Gly 370 375 380 Ser Met Pro Ala Leu Ilie Met Gly Ala Val Pro Ala Thr Glu Lys Ala 385 390 395 400 Ala Ala Asn Giy Phe Asn Ser Leu Met Arg Ser Leu Gly Thr Thr Gly 405 410 415 Ser Ser Ala Val Ile Gly Ala Val Leu Ala Gly Met Met Ser Gly Gly 420 425 430 Val Pro Thr Leu Gly Gly Phe Met Thr Thr Leu Ile Ile Gly Cys Cys 435 440 445 Ala Ala Leu Val Ala Ala Val Ile Ser Tyr Phe Ile Pro Thr Thr Thr 450 455 460 Thr Val Val Glu Ala Lys 465 470 <210> 247 <211> 1770 <212> DNA WO 01/00804 <213> Corynebacteriui glutamicui <220> <221> CDS <222> (101)..(1747) <223> RXN01320 <400> 247 gtgaatggca cgacatgcca caaggcacgc aagetgattt PCT/IBOO/00922 ccaagcctgc tgtcgcaaag caattaaaaa tacttttctt cttagaggtg gattttcaga atg aca tea cag gte Met Thr Ser Gin Val aag Lys ce t Pro gct Ala etc Leu tet Ser ace Thr att Ile ttt Phe eag Gin ggt GI y 150 ceg Pro t eg Ser gte Vali atg Met gee Ala tgg Trp tte Phe gee Al a aac As n 135 ggt Gly gac Asp gee Ala gag Glu ttg Leu etg Leu gt g Val gge Gly ate Ile 120 atg Met ggc Gly gae Asp eae His gaa Gi u geg Al a eea Pro att Ile aag Lys 105 gca Ala aee Thr ttg Leu gaa Glu ace Thr aaa Lys atg Met aeg Thr aee Thr ttg Leu ctg Leu aee Thr atg Met egt Arg tea Ser aee Th r et t Leu att Ile gee Ala ggt Gly tte Phe ttg Leu att Ile 155 ceg Pro gea Ala aaa Lys et t Leu 60 gt t Val1 tte Phe ga e Asp gt g Val1 att Ile 140 ett Leu gta Val1 eca Pro ggt Gi y 45 age Se r ggt Giy etc Leu eag Gin gtg Val 125 gt g Val1 tet Se r aca Thr tat Tyr 30 ege Arg tee Ser gag Glu ttg Leu ttt Phe 110 ggt Gi y get Al a eag Gin aea Thr 15 ggt Gly gtt Val t tg Leu ctt Leu gge Gly ggt Gi y tee Ser eg t Arg gea Ala
I
tea Ser gea Ala ttt Phe eag Gin gge Gi y ace Thr aaa Lys ate Ile ct g Leu 145 ace Thr aaa Lys gea Ala ate Ile aee Thr gt t Val1 at t Ile tae Tyr ggt Gly 130 cag Gin get Ala 115 163 211 259 307 355 403 451 499 547 595 643 ace gee Thr Ala egt gag egt gca aag tac atg Arg Glu Arg 170 Ala Lys Tyr Met gge ate atg ggt tee gtt tte Gly Ile Met Gly Ser Val Phe 175 180 WO 01/00804 gga ctg tcc icc atc cti ggc cca ttg cit ggt qgc Gly Leu Ser Ser Ilie Leu Gly Pro Leu Leu Gly Gly 185 190 tgg tic act Trp Phe Thr gac Asp 195 ggt Gly atc Ile cgt Arg 230 gcc Ala gag Glu gct Ala gtc Val1 gcC Al a 310 cct Pro ctg Leu gig Val atc Ile cca Pro gca Ala 215 ggc Gly acc Thr tgg Trp gcg Ala ccc Pro 295 ggt Gi y acc Thr a ig Met 99C Gly 99C Gly 375 ggc Gly 200 ctg Leu aag Lys acc Thr gca Ala ata Ile 280 a tg Met atc Ile tac Tyr ctg Leu aac Asn 360 atg M4et t gg Trp gitt Val gt c Val1 gca Ala t ca Se r 265 gtg Val1 ggc Gly ggc Gi y ctg Leu atc Ile 345 atc Ile cic Leu cg t Arg gc t Ala t cc S er t tt Phe 250 cca Pro ttc Phe Ctt Leu gt a ValI cag Gin 330 cca Pro gtg ValI atc Ile tgg Trp atc Ile qtt Val 235 gt c Val1 atg Met gitt Val1 tc Phe ggc Gly 315 atg Met at g Met tcc Ser atg Met ggt Gly gct Ala 220 gac Asp ci c Leu at c Ile t tc Phe t cg Ser 300 ctg Leu gitt Val1 atg Met aag Lys gtc Val 380 ct g Leu 205 gig Val1 t gg Trp gca Al a atc Ile gtc Val1 285 aac As n tt Phe cat His atc Ile act rhr 365 ct i Leu igg Trp ctg Leu t tg Leu gtg Val1 gg i 270 ga a Gi u cg c Arg aig Met ggt Gly ggc Gly 350 99c Gi y gc Ala tig Leu ctg Leu gga Gly acc Thr 255 tig Leu aag Lys aac Asn aig Met ct g Leu 335 cig Leu aa g Lys cia Leu aac Asri aaa Lys agc Ser 240 t gg Trp tic Phe cgt Arg i tc Phe ggc Gly 320 aac As n at Ile i ac Tyr gia ValI gt i Val1 ct t Leu 225 aic Ile ggt Gly atc Ile gct Ala gt g Val1 305 acc Thr cc a Pro ggt Gly aag Lys cig Leu 385 cca aic Pro Ile 210 cca gct Pro Ala tic atg Phe Met ggc aat Gly Asn acg aca Thr Thr 275 git gac Val Asp 290 cic acc Leu Thr atc gcg Ile Ala acg caa Thr Gin aca tcc Thr Ser 355 tgg tac Trp Tyr 370 cia tcg Leu Ser ggc Gly cgi Arg gci Al a gaa Giu 260 tig Leu cca Pro c Ala i ac T yr gct Al a 340 act Thr cc a Pro acg Th r aic Ile gaa Giu aic Ile 245 tat T yr gic Val cig Leu gi c ValI atg Met 325 ggi Gly gtg ValI ttc Phe ctg Leu PCT/IBOO/00922 691 7?39 787 835 883 931 979 1027 1075 1123 1171 1219 1267 aca cci tcg gca agc ttg Thr Pro Ser Ala Ser Leu cic ati gga ctg Leu Ile Gly Leu 400 tac itc tic gic Tyr Phe Phe Val 1315 WO 01/00804 WO 0100804PCT/IBOO/00922 gg a Gly aac As n t t Phe ctg Leu qca Ala 470 teec Ser ct t Leu ctg Leu ate ttc ggc ctg ggc Phe Gly Leu Gly tgt gca atg eag att ttg gtt etc ate Cys Ala Met Gin Ile Leu Val Leu Ile gtg cag Val Gin 420 tcc Se r ttc Phe ttt Phe 455 gtg Val gat Asp eca Pro aca Thr ctc t tc Phe ege Arg 440 ate Ile get Aia ttC Phe caa Gin eca Pro 520 etc qd LU eca ate ace atg gtt ggc Pro Ile Thr Met Val Giy 425 430 caa ate ggt gga 9ca gta Gin Ilie Gly Gly Ala Vai 445 tee aac ctg tee gac ega Ser Asn Leu Ser Asp Arg 460 tee atg ggt gaa gaa gge Ser Met Gly Giu Giu Gly 475 tee ggt gca tee aac etc Ser Gly Ala Ser Asn Leu 490 gca etc cgt gaa gca att Ala Leu Arg Glu Aia Ile 505 510 ate tte ttg gcg etc ace Ile Phe Leu Ala Leu Thr 525 ttt ttc ate cqt qaa gat 415 ace Th r gg t Gly t te Phe gca Ala act Thr 495 caa Gin ceg Pro ace Thr gca Ala gaa Giu 465 tac Tyr cac His t et Ser gea Ala tee Ser 435 ate Ile gte Val1 tea Ser gt t Val1 aac Asn 515 gte Vali 1363 1411 1459 1507 1555 1603 1651 1699 1747 1770 cac etc aag gaa. aeg cac gaa Ilie Leu Leu Phe Phe Ilie 535 Arg Giu As~p 540 His Leu Lys 545 Glu Thr His Glu taatgacaca cgaaacttcc gte <210> 248 <211> 549 <212> PRT <213> Corynebacterium giutamicum <400> 248 Met Thr Ser Gin Val Lys Pro Asp Asp Giu Arg Pro Val Thr Thr Ile 1 5 10 Ser Lys Ser Gly Ala Pro Ser Ala His Thr Ser Ala Pro Tyr Giy Aia 25 Ala Ala Thr Glu Glu Ala Val Giu Giu Lys Thr Lys Gly Arg Val Gly 40 Phe Ile Ile Ala Ala Leu Met Leu Ala Met Leu Leu Ser Ser Leu Gly 55 WO 01/00804 Gin Thr Ile Phe PCT/IBOO/00922 Gly Ser Ala Leu Pro Thr Ile Val Gly Giu Leu 70 75 Gl Thr Lys Ile Leu 145 Thr Met Gly Val Leu 225 Ile Gly Ile Ala Va1 305 Val Ile Tyr Gly 130 Gin Ala Gly Trp Pro 210 Pro Phe Gly Thr Val 290 Leu Asr Ser Leu 115 Ala Gly Asp Ser Phe 195 Ile Ala Met Asn Thr 275 Asp rhr His Leu 100 I Phe Leu Ile Val Val 180 Thr Gly Arg Ala Glu 260 Leu Pro Ala Met Pro Met Ala Ala Thr 165 Phe Asp Ile Glu Ile 245 Tyr Va1 Leu fal Thr Ile Phe Gin Gly 150 Thr Gly Gly lle Arg 230 Ala Glu Ala Val Ala 310 Tr; Phe Ala Asn 135 Gly Ala Leu Pro Ala 215 Gly Thr Trp Ala Pro 295 3iy Val Gly Ile 120 Met Gly Arg Ser Gly 200 Leu Lys Thr Ala Ile 280 Met Ile Tyr 114 Ly 10! Al Thi Let Glu Ser 185 Trp Va1 Val Ala Ser 265 Val Gly ly Leu Thr 90 Leu 5 a Leu Thr Met Arg 170 Ile Arg Ala Ser Phe 250 Pro Phe Leu Val Gin b 330 Pro t Ala Gly Fhe Leu Ile 155 Ala Leu Trp Ile Va1 235 Va1 Met Va1 Ehe fly 315 let let Phe Asf Val Ile 140 Leu Lys Gly Gly Ala 220 Asp Leu Ile Phe Ser 300 Leu Va1 Met Leu Gin Val 125 Val Ser Tyr Pro Leu 205 Val Trp Ala Ile Va 1 285 Asn Phe His Ile Leu Phe 110 Gly Ala Gin Met Leu 190 Trp Leu Leu Val Gly 270 Glu Arq Met Gly fly 350 Gly Gly Ser Arg Ala Gly 175 Leu Leu Leu Gly Thr 255 Leu Lys Asn Met Leu 335 Leu Gly Gin Arg Ile Ala Ile 160 Ile Gly Asn Lys Ser 240 Trp Phe Arg Phe Gly 320 Asn Ile Thr Ile Ala Tyr Met Pro Thr 325 Pro Thr Gin Ala Gly Leu Met Leu Ile 340 345 Gly Thr Ser 355 Thr Val Val Gly Asn 360 Ile Vai Ser Lys Gly Lys Tyr WO 01/00804 Lys Trp Tyr Pro Phe Ile Gly 370 375 PCT/IBOO/00922 Met Leu Ile Met Val Leu Ala Leu VJal 380 Leu Leu Ser Thr Leu Thr Pro Ser 385 Tyr ValI Thr Ala Glu 465 Tyr His Phe Phe Leu Ile Gly Ser 435 Leu Ile 450 Asn Val Ala Ser Leu Val Val1 ValI 420 Asn Gly Pro Al a Glu 500 Phe 405 Gin Asn Gly Al a Met 485 Ser 390 Gi y Asn Phe Leu Al a 470 Ser Leu Phe Ser Phe Phe 455 Val Asp Pro Gly Phe Arg 440 Ile Ala Phe Gin Ala Leu Pro 425 Gin Se r Se r Ser Ala 505 Ser Gi y 410 Ile Ile Asn Met Gly 490 Leu Phe Leu 395 Cys Thr Gly Leu Gly 475 Ala Arg Leu Ala Ala Met Gly Ser 460 Giu Ser Giu A~la Leu Met Val1 Ala 445 Asp Giu Asn Ala Leu 525 I le Gin Gly 430 Val1 Arg Gly Leu Ile 510 Thr Gly Ile 415 Th r Gly Phe Ala Thr 495 Gin Pro Ser Tyr Asn Asp Ala Leu Thr Pro Ile 515 520 Ala Val Val Ala Ala Ilie Leu Leu Phe Phe Ile Arg Glu Asp His Leu 530 535 540 Lys Giu Thr His Glu 545 <210> 249 <211> 841 <212> DNA <213> Corynebacteriun glutarnicum <220> <221> CDS <222> (841) <223> FRXA01314 <400> 249 gtgaatqgca cgacatgcca caaggcacgc aagctgattt ccaagcctgc tgtcqcaaag caattaaaaa tacttttctt cttagaggtg gattttcaga atg aca tca cag gtc 115 Met Thr Ser Gin Val 1 aag ccg gac gac gaa cgt ccg gta aca aca att tca aaa agt ggt gca 163 Lys Pro Asp Asp Giu Arg Pro Val Thr Thr Ile Ser Lys Ser Gly Ala 15 WO 01/00804 WO 0100804PCTIBOOIOO922 ct Pro got Ala ct c Leu tct Ser ace Thr att Ile ttt Phe ca g Gin ggt Gly 150 ace Thr gga Gly ggt Gly atc Ile cgt Arg 230 tcg Ser gte Va I atg Met gcc Ala tgg Trp ttc Phe gc Al a aac Asn 135 ggt Gly gee Ala ct g Leu eca Pro gca Al a 215 gee Ala gag Glu t tg Leu otg Leu gt g Val1 Gly ate Ile 120 atg Met gge Gly cgt Arg tee Se r gge Gly 200 ctg Leu ec His qaa Glu gog Al a cca Pro at t Ile aag Lys 105 gca Al a ace Thr ttg Leu gag Glu tee Ser 185 tgg Trp gtt Val aec Thr aaa Lys at q Met aeg Th r a cc Thr t tg Leu etg Leu ace Thr atg Met egt Arg 170 ate I le cgt krg Iet U. a tea Ser acc0 Thr ctt Leu att Ile 75 gee Ala ggt.
GI y tt C Phe ttg Leu att.
Ile 155 gca Ala ott Leu tgg Trp ate Ile gea Ala aaa Lys ctt Leu 60 gtt Val1 ttC Phe ga e Asp gtg Val1 att Ile 140 ott Leu a ag Lys GI y ggt gct kla 220 o ea Pro ggt Gly 45 a go Ser ggt Gly etc Leu eag Gin gtg Val1 125 gtg Val tet Ser tac Tyr cca Pro ct g Leu 205 gtg Ia 1 tat Tyr 30 ego Arg too Se r gag Glu ttg Leu ttt Phe 110 ggt Gly get Al a ea g Gin atg Met ttg Leu 190 tgg Trp etg Leu ggt Gi y gtt Val1 ttg Leu ott Leu gge Gly 95 ggt GI y tee Ser egt Arg gea Ala 9gC Gly 175 ctt Leu t tg Leu ctg Leu qea Ala *gga *Gly ggt IGly Gly 80 cag Gln ege Axg ate Ile qea Al a att Ile 160 ate Ile ggt Gly aac Asn aaa Lys gca Al a ttt Phe cag Gin gg e Gly ace Thr aaa Lys ate Ile etg Leu 145 ace Thr atg Met gge Gly gtt Val1 ott Leu 225 gca Al a ate Ile ace Th r gtt ValI att Ile tao T yr ggt Gly 130 ca g Gin got Al a ggt Gly t gg Trp cca Pro 210 oca Pro act Thr ate Ile att Ile aac Asn tea Ser etc Leu 115 get Al a ggt GI y gat Asp too Ser t to Phe 195 ate I le get Ala gaa gaa Glu Glu gca gee Ala Ala tte ggt Phe Gly cac atg His Met ttg cot Leu Pro 100 tte atg Phe Met ttg gct Leu Ala ate gco Ile Ala gte ace Val Thr 165 gtt tte Val Phe 180 act gao Thr Asp ggc ate Gly Ilie egt gaa Arg Glu ggc aag gte tco Gly Lys Val Ser gtt Val1 235 gao tgg ttg gga Asp Trp Leu Gly ate ttc atg get Ile Phe Met Ala WO 01/00804 PCTIBOO/00922 gcc acc 841 Ala Thr <210> 250 <211> 247 <212> PRT <213> Corynebacterium giutamicum <400> 250 Met Thr Ser Gin Val Lys Pro Asp Asp Giu Arg Pro Val Thr Thr Ile 1 5 10 Ser Lys Ser Giy Ala Pro Ser Ala His Thr Ser Ala Pro Tyr Gly Ala 25 Ala Ala Thr Glu Giu Ala Val Giu Glu Lys Thr Lys Gly Arg Val Gly 40 Phe Ile Ile Ala Ala Leu Met Leu Ala Met Leu Leu Ser Ser Leu Gly 55 Gin Thr Ile Phe Gly Ser Ala Leu Pro Thr Ile Val Gly Giu Leu Gly 70 75 Gly Val Asn His Met Thr Trp Val Ile Thr Ala Phe Leu Leu Gly Gin 90 Thr Ilie Ser Leu Pro Ilie Phe Gly Lys Leu Gly Asp Gin Phe Gly Arg 100 105 110 Lys Tyr Leu Phe Met Phe Ala Ilie Ala Leu Phe Val Vai Gly Ser Ile 115 120 125 Ilie Gly Ala Leu Ala Gin Asn Met Thr Thr Leu Ile Val Ala Arg Ala 130 135 140 Leu Gin Gly Ile Ala Gly Gly Gly Leu Met Ile Leu Ser Gin Ala Ile 145 150 155 160 Thr Ala Asp Val Thr Thr Ala Arg Giu Arg Ala Lys Tyr Met Gly Ile 165 170 175 Met Gly Ser Val Phe Gly Leu Ser Ser Ile Leu Gly Pro Leu Leu Gly 180 185 190 Gly Trp Phe Thr Asp Gly Pro Gly Trp Arg Trp Gly Leu Trp Leu Asn 195 200 205 Val Pro Ile Gly Ile Ile Ala Leu Val Ala Ile Ala Val Leu Leu Lys 210 215 220 Leu Pro Ala Arg Giu Arg Gly Lys Val Ser Val Asp Trp Leu Gly Ser 225 230 235 240 Ile Phe Met Ala Ile Ala Thr WO 01/00804 WO 0100804PCT/IBOO/00922 <210> 251 <211> 803 <212> DNA <213> Corynebacteriun glutamicuw <220> <221> CDS <222> (1)..4780) <223> FRXA01320 <400> 251 gtt gac eca ctg gte ccc atg ggc Val Asp Pro Leu Val Pro Met Gly 1 5 ctt ttc tcg aac: egc aac ttc gtg Leu Phe Ser Asn Arg Asn Phe Val 10 ct C Leu atc Ile acg Thr aca Thr t gg Trp ct a Leu ttC Phe ctc Leu ggt Gly 145 acc Th r qC9 Al a eaa Gin tcc Ser ta c Tyr tcg Se r ttC Phe atc Ile 130 tcC Ser gce Ala t ae Tyr gct Ala act Thr cca Pro a cg Thr gte Val1 115 gtg Val1 aac Asn qt C Val1 atg Met ggt Gi y gt g ValI tte Phe et g Leu 100 ttc Phe cag Gin aac Asn gcc ggt ate ggc gta Ala Gly Ile Giy Val 25 cet ace tac ctg cag Pro Thr Tyr Leu Gin 40 etg atg etg ate cca Leu Met Leu Ile Pro 55 gtg ggc aac ate qtg Val Gly Asn Ile Val 70 atc ggc atg etc atc Ile Giy Met Leu Ile aca cet tcg gca age Thr Pro Ser Ala Ser 105 gga ttc ggc etg gqc Gly Phe Gly Leu Gly 120 aae: tcc: ttc cca ate Asn Ser Phe Pro Ile 135 ttc ttc cgc eaa ate Phe Phe Arg Gin Ile 150 ggc Gly atg Met atg Met tee Se r atg Met 90 ttg Leu t gt Cys ace Th r 9gt Giy :t g Leu 170 ctq Leu qtt Val1 atg Met aag Lys 75 gte Val1 get Ala gca Ala atg Met gga Gly 155 ttt Phe eat His ate Ile acet Thr ctt Leu ct C Leu atg Met gt t ValI 140 gca Ala atg Met ggt Gly gge Gly gge Gly gee Ala att Ile eag Gin 125 gge Gly gta Val1 atg Met ctg Leu ct q Leu aag Lys eta Leu gga Gly 110 a tt Ile ace Th r ggt GI y ggc ace Gly Thr aac eca Asn Pro att ggt Ile Gly tac: aag Tyr Lys gta ctg Val Leu etg tac Leu Tyr ttg gtt Leu Val gcg ace Ala Thr tee gca Ser Ala 160 96 144 192 240 288 336 384 432 480 528 etg ate ggt ge Leu Ile Gly Gly etg Leu 165 ttt ate tee aae Phe Ile Ser Asn tee gac cga ttc Ser Asp Arg Phe ace gaa Thr Glu 175 WO 01/00804 a ac Asri gcc Ala ctt Leu tac Tyr 225 gta Val gaa Gl u gea Ala 180 atg Met tea Ser gee Al a geg Al a ga a Glu 260 gca gtg get tec atg ggt gaa Ala Val Ala Ser Met Gly Glu 185 tee gat ttc tcc ggt gea tee Ser Asp Phe Ser Gly Ala Ser 200 ctt eea caa gca etc eqt gaa Leu Pro Gin Ala Leu Arg Glu 215 ctg aca cca ate tte ttg geg Leu Thr Pro Ilie Phe Leu Ala 230 235 atc etc etc ttt ttc ate egt Ile Leu Leu Phe Phe Ile Arg 245 250 taatgacaca cgaaacttcc gte PCT/IBOO/00922 576 624 672 720 768 <210> 252 <211> 260 <212> PRT <213> Corynebaeteriun giutamicum <400> 252 Val Asp Pro Leu Val Pro Met Gly Leu 1 5 Leu Thr Ala Val Ala Gly Ile Gly Val 25 Ile Ala.Tyr Met Pro Thr Tyr Leu Gin 40 Thr Gln Ala Gly Leu Met Leu Ile Pro s0 55 Thr Ser Thr Val Val Gly Asi Ile Val Trp Tyr Pro Phe Ile Gly Met Leu Ile Leu Ser Thr Leu Thr Pro Ser Ala Ser 100 105 Phe Phe Val Phe Gly Phe Gly Leu Gly 115 120 Leu Ile Val Gin Asn Ser Phe Pro Ile Phe 10 Gi y Met Met Ser Met 90 Leu Cys Th r Asn Phe His Ile Thr Leu Leu Met Val1 Arg Met Gi y Gi y Gi y Al a Ile Gin 125 Gly Asn Phe Met Gly Leu Asn Leu Ile Lys Tyr Leu Val Gly Leu 110 Ile Leu Thr Ala Gly 145 Le u Asn Al a Leu Tyr 225 Val Giu WO 01/00804 130 Ser Asn Asn Phe Ile Gly Gly Leu 165 Val Pro Ala Ala 180 Ser Ala Met Ser 195 Val Giu Ser Leu 210 Asn Asp Ala Leu Val Ala Ala Ile 245 Thr His Glu 135 Arg Ile Ala Phe Gin 215 Pro Leu Ile Gly Gly 155 Asn Leu Ser 170 Met Gly Glu 185 Gly Ala Ser Leu Arq Giu Phe Leu Ala 235 Phe Ile Azg 250 PCT/IBOO/00922 140 Al a Asp Glu Asn Ala 220 Leu Glu Ser Th r 175 Gin Pro Leu Ile Leu 255 <210> 253 <211> 1755 <212> DNA <213> Corynebacteriun giutamicum <220> <221> CDS <222> (1732) <223> RXN02926 <400> 253 ccctgacacc aatcttcttg gcgctcaccc: cgatcgcagt ttttcatccg tgaagatcac ctcaaggaaa cgcacgaAta tcc S er cgc Arg ga a Glu a tg gtc ccc gga cct gcc Vai Pro Giy Pro Ala aaa ggc cgc gcg aag Lys Gly Arg Ala Lys caa caa aag aaa gtc Gin Gin Lys Lys Val atg atg gcc tcc ctt gac gcg cag Asp Ala Gin aag gaa aaa Lys Giu Lys 30 tgg tqg qtc Trp Trp Vai 45 gac cag atg gtc gca Vai Ala 15 act cct Thr Pro ctc agc Leu Ser att ttc agtcgccgcg atcctcctct atg aca cac gaa act 115 Met Thr His Giu Thr 1 gga gat acg aag ctg 163 Gly Asp Thr Lys Leu tca tca atg acg cct 211 Ser Ser Met Thr Pro gcg ctg atg gtc gcc 259 Ala Leu Met Val Ala ggc aca gcc ctg cca 307 WO 01/00804 PCT/IBOO/00922 Met Met Met Ala Ser Leu Asp Gin Met Ile Phe Gly Thr Ala Leu Pro 60 aca Thr ac Thr ctc Leu atc Ile tgg Trp atg Met 150 cgt Arg gtt Val1 ege Arg gte ValI t gg Trp 230 ate Ile ate Ile atc Ile gca Ala 99C Gly ttc Phe ttg Leu 135 atc Ile Gly ctt Leu tgg Trp gcc Ala 215 gat Asp ct g Leu ate Ile gtc Va tac Tyi gac Asr etc Let 120 atc Ile etc Leu ege Arg 99C Gly gea Ala 200 att Ile tae Tyr ttc Phe att Ile :ggt L Gly e ta 7Leu ctg SLeu 105 ate Ile gtc Val teg pSer tac Tyr eca Pro 185 ttc Phe tac Tyr etg Leu ace a Thr 1 gga c Gly L 265 gaa Git ctt Leu gt t Val gge Gly ggc Gly cag Gin atg Met 170 eta Leu tgg rrp ttc Phe ;ge ;iY Icc hr :tg ~eu I tc ILet cc Ala gga Gly tee Se r eq t Arg gea Ala 155 ggt Gly etc Leu atg Met etg Leu aet Thr 235 tgg Trp ate Ilie iGly gaa Glu c gt Ar g gte Val gee Ala 140 ate Ile gte ValI ggt Gi y aae Asn gae Asp 220 tte Phe ggt Giy ate Ile g9C G15 aec Thr a aa Lys ate Ile 125 gt a Val1 ate Ile a tg Met gge Giy ate Ile 205 at t Ile tte Phe gga Gly ace Phr -gtt ~Val -ate Sle ggt *Gly 110 99Cg *Gly eag Gin geg Ala ggt Gly tgg Trp 190 cea Pro eca Pro atg Met tee Ser ac Thr 270 gac Asp atg Met 95 ete Leu ggg Gi y Gi y gae Asp gga Gly 175 tte Phe etg Leu aag Lys ate Ile eag Gin 255 ate Ile eac His 80 etg Leu tte Phe ctt Leu ate Ile gtt Val 160 gte Val1 ace Thr gga Gly aag Lys gtt Val 240 tac Tyr gtt Val atg Met ceg Pro ate Ile gca Ala ggt Gi y 145 gt t Val1 tte Phe gaa Giu ate Ile age Ser 225 gee Ala gag Giu gee %la atg Met ate Ile gga Gi y gga Gly 130 gge Gly eea Pro gga Gly gga Gi y ate Ile 210 gte Val1 gea Al a t gg Trp get tgg Trp tac Tyr gee Ala 115 aa t Asn ggt Gly gea Ala et e Leu eea Pro 195 gee Al a aag Lys aee Thr t et Ser gea Al a 275 gte Val1 gga Gly 100 etc Leu atg Met gga Gly egt Arg tet Se r 180 9ge Gly ate Ile ttc Phe age Ser gat Asp 260 et g Leu ate Ile a ag Lys gge Gly ace Thr etg Leu ga a Gi u 165 gea Ala t gg Trp ggt Gly ege Arg etg Leu 245 eca Pro et g Leu 355 403 451 499 547 595 643 691 739 787 835 883 931 gtt gtt gtg gaa Val Val Val Giu ctg ege gea aaa gat eca ttg gtt eca atg tee tte Leu Arg Ala Lys Asp Pro Leu Val Pro Met Ser Phe WO 01/00804 WO 0100804PCTIIB0O/00922 ttc Phe ggt Gly 310 atg Met atg Met too Ser acc Thr ctg Leu 390 cta Leu gog Al a ggt Gly t tq Leu t ca Se r 470 aac Asn caa Gin 295 atc Ile gt c Vai a tg Met aac Asn t tc Phe 375 tgg Trp gc Ala gtg Val1 t cc Ser gga Gly 455 cca Pro gaaI GluI 280C aac Asn qoa Ala cac His gtC Val1 aca Th r 360 gtg Vali cag Gin atg Met gtc Val1 t ca Se r 440 acc rhr gaa ttg ,eu cg Arc atc Met gga G15~ Gl 345 9ga Gily gca Ala atc: Ile cag Gin gga Gi y 425 ctc: Leu ctc: Leu qaa Giu acg Thr -aac SAsn ttc -Phe atc Ile 330 *atg Met aag Lys ct g Leu gga Gly gt t Val1 410 t co Ser gga Gly atg Met caa Gin Ccg Pro 490 ggt Gly I ttc Phe ggo Gly 315 aac Asn aig Met tac Tyr atc Ile ato Ile 395 ctg Leu gca Aila tcC Ser gaa Glu goo Ala 475 gca kiaI a og Thr 300 ato Ile 9C Al a gg t Giy aaa Lys ttC Phe 380 tao Tyr gtC Val1 acc Th r gcg Al a gaa 460 goo kla ~tc Ele 285 ctc Leu atc Ile acc Thr ac Th r oto Leu 365 ttt Phe cto Leu ctg Le u got Ala otg Leu 445 aga Arg atg Met gt c Val *acc Thr *gaa too Ser 350 ttC Phe
C
Ala ttC Phe atc Ile gtg Val1 430 g to Val1 atg Met gca Ala aat Asn acc Thr tac Tyr gc Ala 335 ato Ile ooa Pro oga Arg gt c Val1 gt t Val1 415 aao Asn ggt Gly cca Pro goo :a a 31n 495 att Ile ott Leu 320 990 Giy tgg Trp ooa Pro atg Met oto Leu 400 cag Gin aao Asn ggo Gi y goa Ala oaa Gin 480 ttg Leu gca Aia 305 009 Pro tao Tyr aot Thr atc Ile gaa Glu 385 9go Gly aao Asn tto Phe atg Met gco Ala 465 ggo Giy coa Pro 290 ggC Gi y ac Thr atg Met ggt Giy Gly 370 gtg Val1 gt C Vali aoo Tb r tto Phe t to Phe 450 atg Met gga Giy aoo Thr ctg Leu tao Tyr ctg Leu atc Ile 355 atg Met too Se r ggo Gly otg Leu cgt Arg 435 gt t Val1 goa Al a ct g Leu gog Alia ato Ile ct C Leu ato Ile 340 c Arg gtg Va 1 aoo Tb r otg Leu oca Pro 420 oaa Gin Gly oaa Gin gao Asp oto Leu 500 ctg Leu cag Gin 325 coa Pro ato Ile gtt Val1 aoo Thr ggt Gly 405 a oo Thr ato Ile aao As n ott Leu too Se r 485 oac His 1027 1075 1123 1171 1219 1267 1315 1363 1411 1459 1507 1555 1603 1651 gat gog tto goo :cc tao aao gao goa cto ato coa Asp Ala Phe Ala 505 ;er Tyr Asn Asp 510 Ala Leu Ile Pro gtg tto tao Vai Phe Tyr 515 WO 01/00804 PCTIIB00/00922 gtg atg atg cca ctg ate ggc atc geg ctg ctt etc ttg ctg ttt att 1699 Val Met Met Pro Leu Ile Gly Ile Ala Leu Leu Leu Leu Leu Phe Ile 520 525 530 aag caa gaa aaa eta cgc gaa ace acc aca gac taaacacaaa aeaaatgaga 1752 Lys Gin Giu Lys Leu Arg Giu Thr Thr Thr Asp 535 540 cct 1755 <210> 254 <211> 544 <212> PRT <213> Corynebacteriun giutamieum <400> 254 Met Thr His Glii Thr Ser Val Pro Gly Pro Ala Asp Ala Gin Val Ala 1 Giy Ser Ala Gi y Met Pro Ile Ala Lys Thr Val1 Leu Val Gly 100 Le u Met 5 Leu Pro Ala Pro Ile Lys Giy Thr Arg Giu Met Thr 70 Thr Leu Ile Trp Lys Gin Met Ile Ala Gly Phe Leu 135 Gly Gin Met Val1 Tyr Asp Leu 120 Ile Leu Arg Ci y Arg 25 ILys Ala Gly Leu Leu 105 Ile Val1 Ser Tyr Pro 185 10 Ala Lys Ser Giu Leu 90 Val1 Gly Gly Gin M1et 170 Leu Lys Val Leu Leu 75 Al a Gi y Ser Arg Al a 155 Giy Leu Lys Trp Asp Gly Giu Arg Val1 Ala 140 Ile Val1 Gly Giu Trp Gin Gly Thr Lys Ile 125 Val1 Ile Met Gi y Lys Val1 Met Val Ile Gi y 110 Gly Gin Ala Gly Trp 190 Thr Pro Leu Ser Ile Phe Asp His Met Leu Leu Phe Giy Leu Gly Ile Asp Val 160 Giy Val 175 Phe Thr Gly Gly Gly Gly Leu Met Ile Glu Gly Pro 195 Gly Trp Arg Trp Ala 200 Phe Trp Met Asn Pro Leu Gly WO 01/00804 PCT/IB00/00922 Ile Ile Ala Ile Gly Val Ala Ile Tyr Phe Leu Asp Ile Pro Lys Lys 220
C
A
4
G
210 Ser Val 225 Ala Ala Glu Trp Ala Ala Val Pro 290 Ala Gly 305 Pro Thr Tyr Met Thr Gly Ile Gly 370 ;lu Val 385 Sly Val sn Thr 'he Phe let Phe 450 la Met 65 ly Gly 215 Lys Thr Ser Ala 275 Met Leu Tyr Leu Ile 355 Met Ser Gly Leu Arg 435 Val Ala Leu Phe Ser Asp 260 Leu Ser Ile Leu Ile 340 Arg Val Thr Leu Pro 420 Gin Gly Gin Asp SArg Leu 245 Pro SLeu Phe Leu Gin 325 Pro Ile Val Thr Gly 405 Thr Ile Asn Leu Ser 485 Trp 230 Ile Ile Val Phe Gly 310 Met Met Ser Thr Leu 390 Leu Ala Gly Leu 3er 170 Asn Asp SLeu SIle Val Gin 295 Ile Val Met Asn Phe 375 Trp Ala Val Ser Gly 455 Pro Glu I Tyr Phe Ile Val 280 Asn Ala His Val Thr 360 Val Gin Met Val Ser 440 Thr ;lu Leu SLeu SThr Gly 265 Glu Arg Met Gly Gly 345 Gly Ala Ile Gin Gly 425 Leu Leu Glu Thr Gly Thr 250 Leu Leu Asn Phe Ile 330 Met Lys Leu Gly Val 410 Ser Gly Met Gln Pro SThr 235 Trp Ile SArg Phe Gly 315 Asn Met Tyr Ile Ile 395 Leu Ala Ser Glu Ala 475 Ala Phe Gly Ile Ala Thr 300 Ile Ala Gly Lys Phe 380 Tyr Val Thr Ala Glu 460 Ala Ile Phe Gly Thr Lys 285 Leu Ile Thr Thr Leu 365 Phe Leu Leu Ala Leu 445 Arg Met Val Met Ser Thr 270 Asp Thr Gly Glu Ser 350 Phe Ala Phe Ile Val 430 Val Met Ala Asn Ile Gin 255 Ile Pro Thr Tyr Ala 335 Ile Pro Arg Val Val 415 Asn Gly Pro Ala Gin Val 240 Tyr Val Leu Ile Leu 320 Gly Trp Pro Met Leu 400 Gin Asn Gly Ala Gin 480 Leu 490 495 Pro Thr Ala His Asp Ala Phe Ala 505 Gly Ser Tyr Asn Asp Ala Leu 510 WO 01/00804 PCT/IBOO/00922 Ile Pro Val Phe Tyr Val Met Met Pro Leu Ile Gly Ile Ala Leu Leu 515 520 525 Leu Leu Leu Phe Ile Lys Gin Glu Lys Leu Arg Giu Thr Thr Thr Asp 530 535 540 <210> 255 <211> 1294 <212> DNA <213> Corynebacteriui glutamicwtm <220> <221> CDS <222> (1294) <223> FRXA01319 <400> 255 ccctgacaCc aatcttcttq gcgctcaccc cgatcgcagt agtcgccgcg atcctcctct ttttcatcCg tgaagatcac ctcaaggaaa cgcacgaata atg aca cac gaa act Met Thr His Giu Thr tcc gtc Ser Val cgc aaa Arg Lys gaa caa Glu Gin atg atg Met Met aca atc Thr Ile acc gca Thr Aia ctc ggC Leu Gly ccc Pro 990 Gly caa Gin atg Met gtc Val1 t ac Tyr gac Asp gga cct Giy Pro cgc gcg Arg Aia aag aaa Lys Lys gCC tcC Ala Ser ggt gaa Gly Glu cta ct Leu Leu ctg gtt Leu Val gcc gac gcg Ala Asp Ala aag aag gaa Lys Lys Glu qtc tgg tgg Val Trp Trp 45 ctt gac cag Leu Asp Gin 60 ctc ggc ggc Leu Gly Gly 75 gcc gaa acc Ala Glu Thr gga cgt aaa Giy Arg Lys cag Gin aaa Lys 30 gtc Val1 a tq Met gt t Val1 atc Ile ggt Gly 110 gtc gca Val1 Aia 15 act cct Thr Pro ctc agc Leu Ser att ttc Ile Phe gac cac Asp His 80 atg ctg Met Leu 95 ctc ttc Leu Phe 1 gga Gly t ca Ser gcg Al a ggc Giy atg Met ccg Pro atc Ile a cg Th r atg Met atg Met 9CC Ala tgg Trp tac Tyr gcc Ala 115 aag ctg Lys Leu acg OCt Thr Pro gtc gCC Val Ala ctg cca Leu Pro gtc atC Val Ile gga aag Gly Lys 100 ctC 9gC Leu Gly 115 163 211 259 307 355 403 451 105 atc ttc ctg atc ggc tco gtc atc 99c ggg Ctt gca gga aat atg acc Ile Phe Leu Ile Gly Ser Vai Ile Gly Giy Leu Ala Gly Asn Met Thr WO 01/00804 120 PCT/IBOO/00922 t gg T rp atg Met 150 cg t Arg gt t Val1 cgc Arg gtc ValI t gg T rp 230 atc Ile atc Ile gt t Val ttc Phe ggt Gly 310 atg Met t tg Leu 135 atc Ile Gly ott Leu tgg Trp gc Ala 215 gat Asp ctg Leu atc Ile gtt Val caa Gin 295 atc Ile gtc Val1 ato gtc Ile Val ctc tog Leu Ser Ogc tac Arg Tyr ggc cca Gly Pro 185 gca ttc Ala Phe 200 att tac Ile Tyr tac ctg Tyr Leu ttc acc Phe Thr att gga Ile Gly 265 gtg gaa Val Giu 280 aac cgc Asn Arg gca atgt Ala Met cac gga a His Gly I ggc cag Gln atg Met 170 cta Leu t gg Trp ttc Phe ggc Gly acc Thr 250 ct g Leu ctg Leu aac Isn :tc ?he ~tc le cgt gc Arg Ala 140 qca atc Ala Ile 155 ggt gtc Gly Val ctc ggt Leu Gly atg aac Met Asn ctg gao Leu Asp 220 act ttc Thr Phe 235 tgg ggt Trp Gly atc ato Ile Ile cgc gca Arg Ala tto acg Phe Thr 300 ggc ato Gly Ile 315 aac gc Asn Ala gti Va.
a t I it atc Met ggC atc Ile 205 att Ile ttc Phe gga Gly acc Thr aaa Lys 285 oto Leu atc Ile acc rhr 3cag ggc atc ggt ggc L Gin Gly Ile Giy Gly 145 gcg gac gtt gtt cca Ala Asp Val Val Pro 160 ggt gga gtc ttc gga Gly Gly Val Phe Gly 175 tgg tto acc gaa gga rTrp Phe Thr Giu Gly 190 oca otg gga atc atc Pro Leu Giy Ile Ile 210 cca aag aag ago gtc Pro Lys Lys Ser Val 225 atg atc gtt goc gca Met Ile Val Ala Ala 240 too cag tao gag tgg Ser Gin Tyr Glu Trp 255 aco ato gtt goc got Thr Ile Val Ala Ala 270 gat oca ttg gtt oca Asp Pro Leu Vai Pro 290 aco aco att gca ggc Thr Thr Ile Ala Gly 305 ggc tao ott cog aco Gly Tyr Leu Pro Thr 320 gaa. goc ggc tao atg Giu Ala Giy Tyr Met 335 ggt Gi y goa Ala oto Leu cca Pro 195 gc Ala aag Lys acc Thr tot Ser gca Ala 275 atg Met ot g Leu tao Tyr ct g Leu gga Gly ogt Arg tot Ser 180 9go Gly at 0 Ile ttc Phe ago Ser gat Asp 260 otg Leu too Ser ato Ile oto Leu ato Ile 340 otg Leu gaa Glu 165 goa.
Al a tgg Trp ggt Gi y ogo Arg otg Leu 245 ooa.
Pro ctg Leu tto Phe ot g Leu ca g Gin 325 cca Pro 547 595 643 691 739 787 835 883 931 979 1027 1075 1123 1171 330 atg atg gto ggc atg atg ggt Met Met Val Gly Met Met Gly 345 aco too ato tgg act Thr Ser Ile Trp Thr 350 ato ogo ato Ile Arg Ile 355 WO 01/00804 tee aaC aca gga aag tac aaa cte Ser Asn Thr Gly Lys Tyr Lays Leu 360 365 ace ttc gtg gea ctg ate tte ttt Thr Phe Val Ala Leu Ilie Phe Phe 375 380 ctg tgg cag atc gga ate tac etc Leu Trp Gin Ilie Gly Ilie Tyr Leu 390 395 <210>; 256 '211> 398 <212> PRT <213> Corynebacterium giutamicu ttc cca cca ate ggc atg gtg gtt Phe Pro Pro Ile Gly Met Val Val 370 gee ega atg gaa gtg tee acc ace Ala Arg Met Giu Val Ser Thr Thr 385 tte Phe PCT/IBOO/00922 1219 1267 1294 <400> 256 Met Thr Ri-s Glu Thr Ser Val Pro Gly Pro Ala Asp Ala Gin Val Ala 1 Gly Ser Al a Gi y Met Pro Ile Al a Gly 145 Val Phe Asp Se r Leu Thr Met Ile Gly Gly 130 Gi y Pro Gi y Thr Met Met Ala T rp Tyr Ala 115 Asn Gly Ala Leu Lys Thr Val Leu Val Gly 100 Leu Met Gly Arg Ser 5 Leu Pro Al a Pro Ile Lys Gly Thr Leu Giu 165 Ala Arg Glu Met Th r Thr Leu Ile T rp Met 150 Arg Val Gly Gin 40 Met Val1 Tyr Asp Leu 120 Ile Leu Arg Gi y Arg Lys Al a Gi y Leu Leu 105 Ile Val1 Ser Tyr Pro 185 Al a Lys Ser Glu Leu Val Gly Gly Gin Met 170 Leu Lys T rp Asp Gly Glu Arg Val Ala 140 Ile Val Gly Glu T rp Gin Gi y Thr Lys Ile 125 Val Ile Met Gly 180 190 Glu Gly Pro Gly Trp Arg Trp Ala Phe Trp Met Asn Ile Pro Leu Gly WO 01/00804 195 200 205 Ile Ile Ala Ile Gly Val Ala Ile Tyr Phe Leu Asp Ilie Pro Lys Lys PCT/IBOO/00922 210 Ser Val 225 Ala Ala Glu Trp Ala Ala Val Pro 290 Ala Gly 305 Pro Thr Tyr Met Thr Gly Ile Gly 370 Lys Th r Ser Ala 275 Met Leu Tyr Leu Ilie 355 Met Arg Leu 245 Pro Leu Phe Leu Gin 325 Pro Ile Val1 Trp 230 I le Ile Val1 Phe Gly 310 Met Met Ser Th r 215 Asp Tyr Leu Phe Ile Ilie Val Val 280 Gin Asn 295 Ile Ala Val His Met Val Asn Thr 360 Phe Val 375 Leu Th r Gi y 265 Gi u Arg Met Gly Gly 345 Gly Ala Gly Thr 235 Thr Trp 250 Leu Ile Leu Arg Asn Phe Phe Gly 315 Ile Asn 330 Met Met Lys Tyr Leu Ile 220 Phe Giy Ile Al a Thr 300 Ile Aila Gly Lys Phe 380 Phe Gly Th r Lys 285 Leu Ile Thr Thr Leu 365 Phe Giu Val Ser Thr Thr Leu Trp Gin Ile Gly Ile Tyr Leu Phe <210> 257 <211> 1510 <212> DNA <213> Corynebacterium glutainicum <22 0> <221> CDS <222> (1487) <223> RXA01578 <400> 257 tgacctcccc tcaaccactc actgaaaaga qaacactqat gtcacttcct gttcagccga gtaaaacctc ggccgccaca gtcataccat tgatg etc gcc ctg ctg gtc gcg 113 Met Ile Ala Leu Leu Val Ala 1 gta ttc gcc ttc cag ctc aac gcc tcc atg ctg gcg ccg gca ctg gcc 161 WO 01/00804 WO 0100804PCTIIB00100922 Val Phe Ala Phe Gin Leu Asn Ala Ser Met Leu Ala Pro Ala Leu Ala 15 a cc Thr ca g Gin cgt Arg at t Ile acc Thr gtg Val caa Gin 120 ggc Gly t tC Phe ctc Leu aag Lys t tg Leu 200 att Ile atg Met act Th r tgg Trp gtC Val1 a tc Ile cca Pro 105 tat Tyr ggC Gi y cgt Arg gca Ala atg Met 185 ctc Leu ctg Leu ga a Gi u gct Al a ggc Gly acc Th r ctc Leu ctg Leu gcg Ala gtg Val1 tcc Ser ctg Leu 170 ga c Asp atg M4et gt g Val act Thr ttc Phe gat Asp gg t Giy ttc Phe tgt Cys cta Leu gac Asp atc Ile 155 cct Pro tg Trp gct Ala gtt Val1 qaa Giu ttc Phe ctg Leu at t Ilie ct g Leu ctg Leu ct t Leu gcg Ala 140 ttc Phe ttC Phe ctt Leu ttC Phe gtg Vai I 220 ctt Le u acc Thr 45 att Ile gga Gly ggC Gi y atc Ile ctc Leu 125 ctt Leu t gg T rp agc Ser ggt Giy aac ksn 20 5 :tg ~eu *aat IAsn 30 *Ala qgt Gly t gt Cys cgC Arg att Ile 110 gga Gi y gct Ala gtc Val1 gtg Val1 gt g Val1 190 gag Giu ttc Phe gca Ala gcg Ala cgc Arg gt t Val1 ctg Leu 95 ctg Leu att Ilie ggt Gly atg Met aag Lys 175 ctg Leu gcC Al a atc Ile aca Thr gcg Ala cgc Arg gtc Val1 80 att Ile cgc Arg gtt Val1 9gC Gi y gct Ala 160 gaa Giu cca Pro ggc Gly atc Ile gct Al a ctg Le u aaa Lys 65 gct Ala caa Gin cag Gin acc Th r tgg Trp 145 gct Ala t cC Ser ctg Leu aa a Lys ggt Gly 225 gcc Ala ttt Phe 50 gtg Val1 gcC Ala gg t Gly cag Gin tct Ser 130 t tg Leu ttc Phe acc Thr gcg Ala Ctc Leu 210 atc Ile caa Gin t CC Ser ctg Leu ttt Phe gtt Val1 gt a Val1 115 gtC Val1 gct Ala tgC Cys gc t Ala gtg Val1 195 ggt Gly gcc Ala at c Ile ct g Leu gtc Val1 gct Ala gct Ala 100 acc Th r aac Asn ga a Giu gct Al a gaa Glu 180 tcC Ser gc Ala gga Gl y ggC Gly ttc Phe qgC Gly ccg Pro Giy aa t As n gt Gly aca Th r gtc Val1 165 gaa Glu att Ile gcg Al a gt C Val1 atg acg Met Thr ctg cca Leu Pro atg atg Met Met aat gtg Asn Val cca acc Pro Thr gaa aag Giu Lys ggt atc Gly Ile 135 ctt ggt Leu Gly 150 gct gcc Ala Ala acc ccg Thr Pro gga tct Gly Ser aac tgg Asn Trp 215 atc ttc Ile Phe 230 209 257 305 353 401 449 497 545 593 641 689 737 785 ttc tac aac att Phe Tyr Asn Ilie gaa aag cgc gtt Giu Lys Arg Val aag cac ccg ctg gtc agt qtt gaa Lys His Pro Leu Val Ser Val Glu tac T yr ace Thr qcg Ala 280 tgg Trp atc Ile a tt Ile gtc Val ggt Gly 360 atc Ile gca Al a gca Ala atg Met ctg Leu 440 WO 01/001804 235 ctc ggt caa Leu Gly Gin 250 atg acc ggt Met Thr Gly 265 cag gat gct Gin Asp Ala tgg aca ctt Trp Thr Leu gcc gga att Ala Gly Ile 315 ggt atc gct Gly Ile Ala 330 gga agc acc Gly Ser Thr 345 att acc tat Ile Thr Tyr2 gtg ctc tccC Val Leu Ser ggt gcc ttc a Gly Ala Phe 395 git tcc acg g Val Ser Thr A 410 tgg gct ggc g Trp Ala Giy V 425 aic cca cgc c Ile Pro Arg P cga cgc Arg Arg gta ttc Val Phe gcc a Ala Asn 285 acc cca Thr Pro 300 Leu Aia gcc acc Ala Thr tcg cat Ser His gca ggt Nia Gly 365 :ct gct ?ro Ala ~ac cta ~sn Leu rca ttc lie Phe tg atc i 'al Ile I ca gaa t ro Giu S 445 acc Thr gcc Ala~ 270 ggt Gly tat Tyr qga Gi y at C Ilie ctc Leu 350 att Ile aac As n ggt agt 3er atc Ele 130 .ca tgg Trp 255 gta Val gcc Ala gcg Aia aaa Lys at c Ile 335 gcg Ala gcc Aila aac Asn gca Ala gac Asp 415 ttg Leu atc i 24( gca Ala etg Met 99C Gi y ct g Leu ttt Phe 320 gg9c Gly tac Tyr aac Asn caa Gin ggt Gly 400 aac Asn gt c la 1 ~cc ttg Ct Leu Le eat gg Asn G1 atg tc.
Met Se: 294 gct 9g Ala GI' 305 gga tac Gly Tyi gtt gCC Val Ala ctc ggc Leu Gij atc atc Ile Met 370 ggc tat Giy Tyr 3B5 att tcc Ile Ser Gly Gly cta gcc Leu Ala get aca Asp Thr 450 Ctg aLeu ctg Leu 275 gcg Ala ttg Leu aag Lys gga Gly atc Ile 355 ctc Leu ct g Leu ttc Phe gga Gly ttC Phe 435 gtg Val PCT/IBOO/00922 agc Ser 260 ctg Leu agc Se r gt a Val1 atc Ile g cc Ala 340 tcC Ser aac Asn cct Pro gcc Ala tac Tyr 420 ctc Leu gca Alia2 245 acc Thr Ccc Pro gt g Val1 ttc Phe gtc Val1 325 a cc Thr atc Ile Gly Gly a tc Ile 405 gCC Ala tqc gcc ctt ctc Leu Leu eec ctt Asn Leu gtg tcc Vai Ser 295 ggt cca Gly Pro 310 ctg caa Leu Gin ttc tta Phe Leu ttc gtg Phe Val ctg ggc Leu Gly 375 atg aac Met Asn 390 ctc ttc Leu Phe gca ggc Ala Gly tcc Ctg Ser Leu aaa gtc Lys Val 455 881 929 977 1025 1073 1121 1169 1217 1265 1313 1361 1409 1457 1507 ~er Ile Thr cag gct gaa gee gcc gct caa gcc gcc agc taaatccaca aactgaacta Gin Ala Glu Giu Ala Ala 460 Gin Ala Ala WO 01/00804 PCT/1B00100922 agg 1510 <210> 258 <211> 465 <212> PRT <213> Corynebacteriun giutamicum <400> 258 Met Ilie Ala Leu Leu Val Ala Val Phe Ala Phe Gin Leu Asn Ala Ser 1 5 10 Met Leu Ala Pro Ala Leu Ala Thr Met Glu Thr Giu Leu Asn Ala Thr 25 Ala Ala Gin Ilie Gly Met Thr Gin Thr Ala Phe Phe Thr Ala Ala Ala 40 Leu Phe Ser Leu Phe Leu Pro Arg Trp Gly Asp Leu Ile Gly Arg Arg 55 Lys Val Leu Val Gly Met Met Ile Val Thr Gly Ile Gly Cys Val Val 70 75 Ala Ala Phe Ala Pro Asn Val Thr Ilie Leu Phe Leu Gly Arg Leu le 90 Gin Gly Val Ala Gly Pro Thr Val Pro Leu Cys Leu Ile Ile Leu Arg 100 105 110 Gin Gin Val Thr Asn Giu Lys Gin Tyr Ala Leu Leu Leu Gly Ile Val 115 120 125 Thr Ser Val Asn Gly Gly Ile Gly Gly Val Asp Ala Leu Ala Gly Giy 130 135 140 Trp Leu Ala Giu Thr Leu Gly Phe Arg Ser Ile Phe Trp Val Met Ala 145 150 155 160 Ala Phe Cys Ala Val Ala Ala Leu Ala Leu Pro Phe Ser Val Lys Glu 165 170 175 Ser Thr Ala Giu Giu Thr Pro Lys Met Asp Trp Leu Gly Val Leu Pro 180 185 190 Leu Ala Val Ser Ile Giy Ser Leu Leu Met Aia Phe Asn Glu Ala Gly 195 200 205 Lys Leu Gly Ala Ala Asn Trp Ile Leu Val Val Vai Leu Phe Ile Ile 210 215 220 Gly Ilie Ala Giy Val Ile Phe Phe Tyr Asn Ile Glu Lys Arg Val Lys 225 230 235 240 His Pro Leu Val Ser Val Glu Tyr Leu Gly Gin Arg Arg Thr Trp Ala 245 250 255 WO 01/00804 WO 0100804PCT/IBOO/00922 Leu Leo Leu Ser Thr Leu Leu Thr Met Thr Gly Val Phe Ala Val Met Asn Met Ala 305 Gly Val1 Leo Ile Gly 385 Ilie Gly Leu Gly Ser 290 Gi y Tyr Ala Gly Met 370 Tyr Ser Gly Al a 260 Leu S er Val1 Ile Al a 340 Se r Asn Pro Ala Tyr 420 Leo Pro Val1 Phe Val1 325 Th r Ilie Gly Gly Ilie 405 Ala Cys Asn Val Gi y 310 Leo Phe Phe Leo Met 390 Leo Al a Ser Leo Se r 295 Pro Gin Leu Val1 Gi y 375 Asn Phe Gly Leo Ala 280 Trp Ile Ile Val1 Gly 360 Ile Ala Ala Met Leu 265 Gin Asp Trp Thr Ala Gly Gly Ile 330 Giy Ser 345 Ile Thr Val Leo Gly Ala Val Ser 410 Trp Ala 425 Ile Pro Ala Leu Ile 315 Al a Thr Tyr Ser Phe 395 Thr Gly Arg Ala Asn 285 Thr Pro 300 Leo Ala Ala Thr Ser His Ala Gly 365 Pro Ala 380 Asri Leu Ala Phe Val Ilie Pro Giu 445 270 Gi y Tyr Gly Ile Leu 350 Ile Asn Gly Se r Ile 430 Se r 440 Asp Thr Val Ala Ala Lys Val Gin Ala Glu Glu Ala Ala Gin Ala Ala 450 455 460 Se r 465 <210> 259 <211> 1470 <212> DNA <213> Corynebacteriom giotamiconi <220> <221> CDS <222> (101)..(1447) <223> RKA02087 <400> 259 aatcggattc atgctgtgtq gtgtgatcag tttgctggct gcggtcgcat ggatcttcgg WO 01/00804 ccgggagacg etgccaacgg cgaaagtega geaggtataa PCTIBOO/00922 115 atg acg eca att Met Thr Pro Ile 1 gag Glu etc Leu caa Gin gtt Val1 ggt GI y ttt Phe ttg Leu ccg Pro gga Gly ttc Phe 150 get Ala gtg Val tgg Trp tec Se~ ac~ Thi ga Glu tat Tyr gat Asp a cc Thr att.
Ile eag Gin gee Ala 135 ggg Gl.y gtg ValI geg Ala ctc Leu :agg r Arg I ctg Leu gat Asp ttg *Leu gt Arg etc *Leu get Al a ec Pro 120 gee Ala e ca Pro ttc Phe cgt Arg tcg Ser 200 geg Al a ct t Leu ttg Leu etc Leu tat Tyr geg Ala get Ala 105 ctg Leu ace Thr gtt ValI ttg Leu tat Tyr 185 ggt 31y tg Tr 1( ga AsI ggt G13 act Th z gga Gly geg Ala ege Arg age Ser ggg GI y ate Ilie gtt Val1 170 Itg la 1 jeg gaaa p Lys 0 ccaa D Gin geg ,Ala ttt Phe cag Gin 75 ttg Leu 9gg Ala atc Ile gtg Val ggt Gly 155 tat Tyr cet a Pro I gte t get Ala t eg Se r age Ser gcg Al a 60 cga Arg gee Ala gt g Val1 att Ile t gg r rp 140 ggt Itg lal ~aa ~ys cea etc Let ttc Le.
etc Leu 45 gtg ValI aa t Asn tgt Cys cag Gin cac His 125 agt.
Se r gtt Val1 ecg Pro ct t Leu :tt gge 1Gly gtg 1Val 30 aac IAsn pcca Pro att Ile gta Val1 ggc Gly 110 aag Lys get Ala ct g Leu etc Leu ec Pro 190 gtt get Ai 11 get Ala caa Gir ctcg Leu tat Tyr ttt Phe 95 etg Leu att Ile gt t Val1 gtg Val1 gga Gly 175 aeg rhr get tta ILeu gte Val geg Ala ttg Leu ctt Leu 80 gca Al a ggc Gi y ttc Phe gee Ala ggg Gly 160 ttg Leu gga GI y gta Val agt Sei ge Ala gtc Val att gc Ala eca Pro gga Giy 9gg Ala tea Ser 145 tgg Trp ate Ile ace Thr ct t Leu gtt 7Val ctg Leu tgg Trp act Thr gge Gly age Ser tet Ser eat His 130 tea Se r ate Ile tee Sen t eg Sen ggt Gly 210 9gg Giy eca Pro gt g Val1 ggg Gly atg Met ate Ile ct t Leu 115 gat Asp get Al a age Ser eta Leu aag Lys 195 gtg Val ctg Leu aag Lys tea Sen ege Arg get Ala gaa Glu 100 ct t Leu cgt Arg gga Gly tgg Tnp t tt Phe 180 ate Ile gtt V/al ttt Phe att Ile geg Ala ttg Leu gt g Val1 tgg Trp aat As n agg Arg ct t Leu egt Arg 165 atg Met gat Asp et t Leu 163 211 259 307 355 403 451 499 547 595 643 691 739 dla Val Ser Leu Val Ala 205 gee ttg eag eag ggg eca gaa ett ggg tgg gga aca etg att. tgg gtg WO 01/00804 PCT/IBOO/00922 Ala Leu Gin Gin Gly Pro Giu Leu Gly Trp Gly Thr Leu Ile Trp Val 215 220 225 tee ctt gc gtt ggt att qct gca gct gtg cte ttt ata tgg atg caa 8135 Ser Leu Ala Val Giy Ile Ala Ala Ala Val Leu Phe Ile Trp Met Gin 230 235 240 245 aca aga tee aag gcg cca etg atg ccg ttg agg att ttc aag acg cgc 883 Thr Arg Ser Lys Ala Pro Leu Met Pro Leu Arg Ile Phe Lys Thr Arg 250 255 260 aac tte gcg ate ggt gca ttt tcg atc ttc agc etg ggc ttt acg gtg 931 Asn Phe Ala Ile Giy Ala Phe Ser Ile Phe Ser Leu Gly Phe Thr Val 265 270 275 tat tce gtt aat ttg ccc atc atg ttg tat ctq eaa aeg gct cag gga 979 Tyr Ser Val Asn Leu Pro Ilie Met Leu Tyr Leu Gin Thr Ala Gin Giy 280 285 290 atg tcg teg eag ttg gcc ggt ttg atg ttg gtt ccg atg ggc atc aic 1027 Met Ser Ser Gin Leu Ala Giy Leu Met Leu Val Pro Met Gly Ile Ile 295 300 305 tct gtg gtg atg tca eca gta att gga cga ttg gtg gat egc ctq gea 1075 Ser Val Val Met Ser Pro Val Ile Gly Arg Leu Val Asp Arg Leu Ala 310 315 320 325 cca gga atg atc tcc aag atc gga ttc ggc gcg etg att ttc teg atq 1123 Pro Giy Met Ilie Ser Lys Ile Gly Phe Gly Ala Leu Ilie Phe Ser Met 330 335 340 gcg ttg atg get gte ttt atg ate gee aac cta tcg ceg tgg tgg eta 1171 Ala Leu Met Ala Val Phe Met Ilie Ala Asn Leu Ser Pro Trp Trp Leu 345 350 355 etc ate ceg att att ttg tte ggt age tec aac gcg atg agt ttt gea 1219 Leu Ile Pro Ilie Ile Leu Phe Gly Ser Ser Asn Ala Met Ser Phe Ala 360 365 370 ccg aac tet gtg att get ctg cqt gat gtt ccg eag gat tta gtg gge 1267 Pro Asn Ser Val Ile Ala Leu Arg Asp Val Pro Gin Asp Leu Vai Gly 375 380 385 tet get tct ggt ttt tac aac ace tca ege eag gtg ggc get gtt ttg 1315 Ser Ala Ser Giy Phe Tyr Asn Thr Ser Arg Gin Val Gly Ala Val Leu 390 395 400 405 ggc gec get ace ttg ggc get gtg atg caa ata gga gtg ggc acg gtg 1363 Giy Ala Ala Thr Leu Gly Ala Val Met Gin Ile Giy Val Giy Thr Val 410 415 420 tec tte ggt gtt gec atg ggt geg gca atc ctg gtg aca ctc gtg ccc 1411 Ser Phe Gly Val Ala Met Gly Ala Ala Ile Leu Val Thr Leu Val Pro 425 430 435 tta ate ttt ggg ttc eta geg gta ace eaa ttt aga tagttgetee 1457 Leu Ile Phe Gly Phe Leu Aia Val Thr Gin Phe Arg WO 01/00804 440 445 gattttctca cga <210> 260 <211> 449 <212> PRT <213> Corynebacteriut glutamicum <400> 260 Met Thr Pro Ile Val Giu Ser Arg Ala PCT/IB00100922 1470 1 Ser Val Ala Leu Val Trp Ile Thr Ala Gly Pro Ser Gly Ser Ala His 130 Ser Ser 145 Trp Ilie Ile Ser Thr Ser Leu Gly 210 Thr Leu 225 Gly Pro Val1 Gi y Met Ile Leu 115 Asp Ala Ser Leu Lys 195 Val1 Ile 5 Leu Phe Leu Lys Ile Gin Ser Ala Val Arg Leu Gly 70 Ala Val Phe Glu Trp Leu 100 Leu Asn Pro Arg Arg Gly Giy Leu Phe 150 Trp Arg Ala 165 Phe Met Val 180 Ile Asp Trp Val Leu Ala Trp Val Ser 230 Thr Glu Tyr 55 Asp Thr Ile Gln Ala 135 Gly Val1 Al a Leu Leu 215 Leu Leu Leu Asp Leu 40 Leu Leu Arg Tyr Leo Ala Ala Ala 105 Pro Leo 120 Ala Thr Pro Val Phe Leu Arg Tyr 185 Ser Gly 200 Gin Gin Ala Val Trp Lys Asp Gin Gly Ala Thr Phe Giy Gin Ala Leu Arg Ala Ser Ile Giy Val Ile Gly 155 Val Tyr 170 Val Pro Ala Val Gly Pro Gly Ile 235 Ala Leu Ser Leo Ser Leo Ala Val Ar g Asn Ala Cys Val Gin Ile His 125 Trp Ser 140 Gly Val Val Pro Lys Leu Ser Leo 205 Glu Leo 220 Ala Ala Phe Ilie Trp Met Gin Thr Arg Ser Lys Ala Pro Leu Met Pro Leo Arg WO 01/00804 WO 0100804PCT/IBOO/00922 Lys Thr 260 Phe Thr 275 Ala Gin Giy Ilie Arg Leu Phe Ser 340 Trp Trp 355 Ser Phe Leu Vai Ala Vai Gly Thr 420 Phe Ala Ser Val 280 Ser Ser 295 Val Vai Gly Met Leu Met Ile Pro 360 Asn Ser 375 Ala Ser Ala Ala Phe Gly Ile 265 Asn Gin Met Ile Ala 345 Ile Val Gi y Thr Val1 425 Val Thr Leu Val Pro Leu Ile Phe Giy Phe Leu Ala Val Thr Gin Phe <210> 261 <211> 1338 <212> DNA <213> Corynebacteriun giutamicwn <220> <221> COS <222> (1315) <223> RXA02088 <400> 261 agagcaccca agcgacattg ttcgataata tgttctatta ttggtattaa tactggtcag ctagatataa aaggggcgca gggctagcct tggqtgtgaa atg tta act caa. aaa 115' Met Leu Thr Gin Lys WO 01/00804 WO 0100804PCTIIBOO/00922 ata Ile gtt Val1 att Ile agt S er a tg Met act Thr cag Gin tee Ser ccg Pro etg Leu 150 ttg Leu get Ala cgg Arg gaa Glu gtq Val t tg Leu geg Ala tcg Ser ggt Gly gaa Glu acc Thr gtg ValI 135 ttt Phe gge Gly gca Ala aag Lys tta gag Leu Glu gct gcg Ala Ala eca cag Pro Gin gtg gtg Val Val ggg aqt Gly Ser tta etc Leu Leu tac tgg Tyr Trp 105 atg ttt Met Phe 120 gag atc Glu Ilie ggc aat Gly Asn atg egg Met Arg ctt gtt Leu Val 185 get gat Ala Asp 200 gct aaa Ala Lys ttt att Phe Ile ttt gtg Phe Val tee ate Ser Ile ttg atc Leu Ile 75 aec gtg Thr Val cag att Gin Ile acg gtc Thr Val cgc ggg A-rg Gly att att Ile Ile 155 tgg ccg Trp Pro 170 gtg tgg Val Trp age aat Ser Asn cca aaa Pro Lys att gcg Ile Ala gte ggt Val Gly ttt gcg Phe Ala 60 gat aag Asp Lys get ate Ala Ile etg etg Leu Leu tct gee Ser Ala 125 egg tgt Arg Cys 140 ggc ceg Gly Pro tte gcq Phe Ala tgg egg Trp Arg agt gtg Ser Val 205 ate Ile ct g Leu 30 ttt Phe ggC Gly ate Ile aee Th r et t Le u 110 atg Met t eq Ser gtt Val att Ile atg Met 190 e eq Pro eea gag Pro Giu gge tat Gly Tyr gat gta Asp Val gee egg Ala Arg ggt tee Gly Ser aeg ggg Thr Gly egt gge Arg Gly gge etg Gly Leu teg gta Ser Val gtg qgt Val Gly 160 tat ggt Tyr Gly 175 ceg aaa Pro Lys gcg ttg Ala Leu gag Giu Gly agt Ser t tg Leu egt Arg ett Leu ate Ile ate Ile tat Tyr 145 get Al a get Al a ace Thr ege Arg tgg Trp at t Ile gca Al a ttt Phe gtg Val1 geg Al a gg t Gi y 115 aag Lys ag t Ser atg Met gt t Val gat Asp 195 get Ala att aag gat tet gee Ile Lys Asp Ser Ala 215 tac egc teg geg ttg ttt agt get ttt gee aat Ala Phe Ala Asn Tyr Arg 220 Ser Ala Leu Phe Ser 225 WO 01/00804 WO 0100804PCT/1800/00922 ggt Gly 230 gca Ala gcg Ala tca Ser aat Asn ctg Leu 310 cca Pro gga Gly gt t Val a tc Ile tgg Trp 390 tgg tcg Trp Ser get gca Ala Ala ttc gcc Phe Ala gat cgc Asp Arg 280 gea gtg Ala Val 295 ate acg Ile Thr agt cag Ser Gin aaa gtc Lys Vai ggc ccg Gly Pro 360 gga ttc Gly Phe 375 ate ttc Ile Phe aae ttt ggt gtg Asn Phe Gly Val 235 ttt age aat ggc Phe Scr Asn Gly 250 gct gga aat get Ala Gly Asn Ala 265 att ggc cgt aaa Ile Gly Arg Lys tte acg gca atg Phe Thr Ala Met 300 gta tet geg ttg Val Ser Ala Leu 315 eag geg gtg etc Gin Ala Val Leu 330 tta gcg aat tte Leu Ala Asn Phe 345 att etc gta ggc Ile Leu Val Gly atg ctg tgt ggt Met Leu Cys Gly 380 gge egg gag acg Gly Arg Glu Thr egt Arg gga Gly ttg Leu ceg Pro 285 atc Ile gea Al a get Ala ea a Gin atg Met 365 gtg Val gtg Val get Ala tgt Cys 270 atg Met gg a Gi y ggt Gly gat Asp atg Met 350 ate Ile ate Ile geg Ala att Ile 255 ci g Leu att Ile ttc Phe get Ala gtt Val 335 geg Ala gca Al a agt Ser gt t Val1 240 geg Al a ea a Gin att Ile g ge Giy ggt Gly 320 ata Ile eag Gin gaa Giu ttg Leu cit eca Leu Pro ggt ttt Gly Phe tte geg Phe Ala tee ggg Ser Gly 290 aca gaa Thr Giu 305 geg ggC Ala Gly gat tee Asp Ser gat ttc Asp Phe cag gea Gln Ala 370 ctg get Leu Ala 385 ctg Leu gc Al a ggC Gi y 275 et g Leu gtg Val tg Leu ege Arg ggt Gly 355 9gc Gly geg Ala gee Ala 245 get Ala etc Leu gte Val1 ate Ile aat Asn 325 gge Gl y at t Ile caa Gin gca Ala 835 883 931 979 1027 1075 1123 1171 1219 1267 1315 1338 etg eca aeg geg aaa gte gag eag gta Leu Pro Thr Ala Lys Val Glu Gin Val taaatgaege eaattgtgga gte <210> 262 <211> 405 <212> PRT <213> Corynebacteriui giutamicum (400> 262 Met Leu Thr Gin Lys Ile Glu Leu Glu Ala Lys Pro Lys Ile Pro Giu 1 5 10 WO 01/00804 WO 0100804PCT/IBOO/00922 Glu Ile Trp Val Leu Val Val Ala Ala Phe Ile Ile Ala Leu Gly Tyr Gly Ser Leu Arg Leu Ile Ile Tyr 145 Ala Al a Thr Arg Ser 225 Leu Gly Phe Se r Leu Phe Leu Arg Val1 Al a Val1 130 Ala Ala Ser Asn Phe 210 Ala Pro Phe Ala Gly 290 Ile Ala Ala Ala Phe Ala Val Tyr Ala Leu 100 Gly Ile 115 Lys Met Ser Ser Met Ser Val Gly 180 Asp Ser 195 Ala Glu Phe Ala Leu Phe Ala Met 260 Gly Asp 275 Leu Ile Pro Al a Pro Leu Al a Gly Ala Phe Gi y 165 Leu Leu Ala Asn Ala 245 Al a Leu Val1 Ile Ser Met 70 Thr Gin Se r Pro Leu 150 Leu Ala Arg Ilie GI y 230 Al a Al a Ser Asn Leu Al a Ser Gi y Glu Thr Val 135 Phe Gly Ala Lys Lys 215 T rp Ala Phe Asp Ala 295 Pro Val Gly Leu Tyr Met 120 GI u Gly Met Leu Ala 200 Asp Ser Ala Al a Arg 280 Val1 Gin Val1 Se r Le u Trp 105 Phe Ile Asn Arg Val 185 Asp Ser Asn Phe Al a 265 I le Phe Phe Ser Leu Thr Gin Thr Arg Ile Trp 170 Val1 Ser Ala Phe Ser 250 Gly Gly Thr ValI Ile Ilie 75 Val1 I le Val Gly Ile 155 Pro T rp Asn Tyr GI y 235 Asn As n Arg Ala Val Arg Ser Gly Gi y Leu Val1 Gly 160 Gi y Lys Leu Phe Val1 240 A1a Gin I le Gly Gly 320 Thr Giu Val Trp Ilie Leu Ile Thr Val Ser Ala Leu Ala Gly Ala Ala Asp Asp Gin Leu 385 Lys WO 01/00804 Gly Leu Leu Ser Arg Pro 340 Phe Gly Ala 355 Ala Gly Phe 370 Ala Ala ValI Val Glu GinI Pro Val1 Ile T rp 390 Ser Gin Gin Ala 330 Lys Val Leu Ala 345 Gly Pro Ilie Leu 360 Gly Phe Met Leu 375 Ile Phe Giy Arg Val Leu Ala Asp Val Ile 335 Asn Phe Gin Met Ala Gin 350 Val Gly Met Ile Ala Giu 365* Cys Gly Val Ile Ser Leu 380 Glu Thr Leu Pro Thr Ala 395 400 PCT/IBOO/00922 <210> 263 <211> 1239 <212> DNA <213> Corynebacteriun glutamicum <2 <221> CDS <222> (101)..(1216) <223> RXA00764 <400> 263 tactgcgtcg gatccgctga tgcttgcaga atcggacagt acctgggacg actggattat taggggtgga attttcgctc agc Ser aat Asn cct Pro cac His gat Asp gt g t tg Leu gag Glu ttg Leu gga Gi y ga t Asp aat ct a Leu acc Thr gcg Ala cat His att Ilie tta t ta Leu cag Gin ga t Asp gag Giu ccc Pro ggg ga t Asp acg Thr ggt Giy 45 gaa Glu gcg Ala tcg gatgggccgt ctgcgcctgc atg aca ctc aag act Met Thr Leu Lys Thr 1 gtt ctt ctg att gcg Vai Leu Leu Ile Ala ttc cgt cgt gtg gtg Phe Arg Arg Val Val gaa gcg agg ttt acg Glu Aila Arg Phe Thr ggt ttg acg gtg gat Gly Leu Thr Val Asp ggc acc qtC aac gaa Gly Thr Val Asn GiU gat ttt aga aac ctt WO 01/00804 WO 0100804PCTIIBOO/00922 Val Ile Asn Gly Leu Leu Gly Ser Ala Glu Gly Asp Phe Arg Asn Leu 95 100 gag Glu ttt Phe gc Al a gt Gi y 150 gc t Al a aga Arg ott Leu gag Glu atg Met 230 cct Pro ttt Phe ga t Asp gc Al a ct g Leu 135 acg Th r g gg Gly t ct Ser cgg Arg gcg Ala 215 ctg Leu gtg Val1 Gi y ttg Leu cgt Arg 120 gtq Val1 t gg T rp ttt Phe ttc Phe gog Ala 200 gtg Val ctt Leu gtg Val ttg Leu co PrC 105 gcj Al a gag Glu aag Lys gg t Gi y Gly 185 tgg Trp gac Asp gcc Al a aca Th r Ict rhr gcg Ala ctt Leu ttq Leu 9gt Gly at t Ile 170 ttt Phe gtg Val1 ago Ser tcg Ser aat Asn 250 agt Ser att I l( ggt Glj att Ile ga t Asp 155 gat Asp gcg Ala aaa Lys aaa Lys aat Asn 235 cog Pro gtg Ja 1 *gcg gtg Ala Val *tao ccc Tyr Pro 125 *cgg aag *Arg Lys 140 gat cag Asp Gln gcg gat Ala Asp .got tca Ala Ser act cag Thr Gin 205 ggg cac Gly His 220 acc aat Thr Asn cag aat Gin Asn cga gga Arg Gly cat ggt His Gly 285 ttc Leu 110 act Thr aac Asn gyg Gi y gtt Val1 cog Pro 190 att Ile aaa Lys ccg Pro tot Ser ttc Phe 270 Cgg Arg I CC IPrc gac Asr cac His~ act Thr att Ile 175 t tg Leu aag Lys t tg Leu t gg Trp ttt Phe 255 ggg Gi y aag Lys acg Thr ccg )Pro acc Thr cgt Arg 160 gc Al a ttg Leu cca Pro caa Gin act Thr 240 gao Asp gga Gly t tg Leu aaa Lys ggq tot Gly Ser tat gct Tyr Ala 130 aga act Arg Thr 145 tgg ttc Trp Phe aqg gto Arg Val tat otg Tyr Leu cog aaa Pro Lys 210 aaa gag Lys Glu 225 ttt ttg Phe Leu aca ggt Thr Gly gtg gca Val Ala gag aag Glu Lys 290 gta acg Val Thr 305 gc Al a 115 gc Al a atc Ile gcg Al a gaa Giu cag Gin 195 att Ile gaa Glu gg t Gly ctg Leu gcg Ala 275 ttg Leu ctc Leu aat Asn gct Ala acc Thr gt t Val1 Arg 180 gtg Val1 acc Thr gtg ValI cy Pro ggg Gly 260 atg Met atc Ile acg Tr gtg ValI gat Asp ttg Leu aa t As n 165 gcg Ala agt Se r gtg Val1 cca Pro ott Leu 245 ctt Leu atg Met gct Al a tgo Cys 451 499 547 595 643 691 739 787 835 883 931 979 1027 1075 265 cac ctg att ggc gtg gg His Leu Ile Gly Val Gly 280 aag cgc acc att got ttt Lys Arq Thr Ilie Ala Phe gat gog gag Asp Ala Glu -295 300 gao ago gat Asp Ser Asp cay ogt ttc caa gtt Gin Arg Phe Gin Val gat Asp ggt gag tat gaa gyc aaa cca Gly Glu Tyr Glu Gly Lys Pro WO 01/00804 WO 0106804PCT/IBOO/00922 310 315 320 325 aca aaq gtq qtg ttg gaa tca atc act gat gcg gtg cga gtg tat gcg Thr Lys Val Val Leu Glu Ser Ile Thr Asp Ala Val Arg Val Tyr Ala 330 335 340 ccg aag acg cat ccg aca ccg ccg atc atg aat tgq gct gtc cat ttg Pro Lys Thr His Pro Thr Pro Pro Ile Met Asn Trp Ala Val His Leu 345 350 355 ttt aag cac gtc cgt gat ttc ctc cgg gtg cgc acg ttt ggc atc Phe Lys His Val Arg Asp Phe Leu Arg Val Arg Thr Phe Gly Ile 360 365 370 taggattcat cggagttttc tic <210> 264 <211> 372 <212> PRT <213> Corynebacteriun glutamicum <400> 264 Met Thr Leu Lys Thr Ser Val Leu Ala Leu Leu Leu Asp Asn Val His 1123 1171 1216 1239 1 ValI Phe Glu Gly Gly Asp Gly Tyr Arg 145 Trp Leu Leu Arg Arg Ala Arg Leu Thr Thr Val Phe Arg Ser Ala 115 Ala Ala 130 Thr Ile Phe Ala Ile Val Phe Val1 Asn As n 100 Asn Ala Thr Val Ala Val Thr Asp Glu Leu Val1 Asp Leu Asn Asn Pro His As p 70 Val1 Glu Phe Al a GI y 150 Ala Pro Al a Tyr Phe Ile Asp Ala Leu 135 Thr Gly Glu Leu 40 Gly Asp Asn Leu Arg 120 Val1 Trp Phe Ser 25 Met Gly Val Gly Pro 105 Ala Glu Lys Gly Thr Leu Ala Ile 75 Leu Ile Gly Ile Asp 155 Asp Thr Gly Glu Ala Ser Val1 Pro 125 Lys Gin Asp Gin Val1 Met Gl y Al a Leu 110 Th r Asn Giy Val Leu Leu Ala Asp Gly Thr Pro Thr Arg 160 Al a Arg Val Glu Arg Ala Arg Ser Phe Gly Phe Ala Ala Ser Pro Leu Leu WO 01/00804 180 PCT/1B00100922 Tyr Pro Lys 225 Phe Thr Val1 Giu Val1 305 Tyr Val1 Trp Thr *Leu *Lys 210 Giu Leu Gi y Ala Lys 290 Thr Giu Arg Al a Phe 370 Gin 195 Ile Giu Gly Leu Al a 275 Leu Leu Gly Val1 Val 355 Gly Val1 Ser Leu Arg Ala Trp 200 Val Lys Thr Gin Thr Val1 Pro Gly 260 Met Ile Thr Lys Tyr 340 His Ile Val1 Pro Leu 245 Leu Met Al a Cys Pro 325 Al a Al a 215 Leu Val1 Gly Leu Arg 295 Ser Lys Lys *Val Leu Val Leu Ile 280 Thr Asp Val Thr His 360 Asp Ala Thr Thr 265 Gly Ile Gin Val1 His Ser Ser Asn 250 Se r ValI Ala Arg Leu 330 Pro Lys Asn 235 Pro ValI Gly Phe Phe 315 Glu Thr Gi y 220 Th r Gin Arg His Asp 300 Gin Se r Pro 205 His As n Asn Gl y Gi y 285 Asp Val Ile Pro Leu 365 190 Ile Lys Pro Lys Leu Gin Pro Trp Thr 240 Ser Phe Asp 255 Phe Gly Gly 270 Arg Lys Leu Ala Glu Lys Asp Gly Glu 320 Thr Asp Ala 335 Ile Met Asn 350 Arg Val Arg Leu Phe Lys Val Arg Asp Phe <210> 265 <211> 271 <212> DNA <213> Corynebacteriui giutamicum <220> <221> CDS <222> (101)..(271) <223> RXN03125 <400> 265 tgacaccggc gcgacgtatg gcattactgg cgtcacccca atttacgatg acatctctgc tcgcctcggc gacgtcctgg ttccttacgt tctgatcgtt ttg gtt cta gcg tiC 115 Leu Val Leu Ala Phe 1 ctc gtg ctg ttg ctc gig ttc cgg icc ait tgg gic cca ttg atc gcg 163 WO 01/00804 PCTIBOO/00922 Leu Val Leu Leu Leu Vai Phe Arg Ser Ile Trp Val Pro Leu Ile Ala 15 gct ctg ggc ttt ggc ttg tca gtt ctg gct acc ttt ggt gct acc gtg 211 Ala Leu Gly Phe Gly Leu Ser Val Leu Ala Thr Phe Gly Ala Thr Val 30 gcg atc ttc caa gaa gqt gct ttc ggc atc atc gac gat cct cag cca 259 Ala Ile Phe Gin Glu Gly Ala Phe Giy Ilie Ile Asp Asp Pro Gin Pro 45 ctg ctg tgc ttc 271 Leu Leu Cys Phe <210> 266 <211> 57 <212> PRT <213> Corynebacterium giutamicum <400> 266 Leu Val Leu Ala Phe Leu Val Leu Leu Leu Val Phe'Arg Ser Ile Trp 1 5 10 Val Pro Leu Ile Ala Ala Leu Giy Phe Gly Leu Ser Val Leu Ala Thr 25 Phe Gly Ala Thr Val Ala Ile Phe Gin Glu Gly Ala Phe Gly Ile Ile 40 Asp Asp Pro Gin Pro Leu Leu Cys Phe <210> 267 <211> 1443 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> (101)..(1420) <223> RXN01553 <400> 267 atgatgatgt cctcagcaag tccaaqcqcc: aagccatgct ggaaacaatt ctcqagctga taccaagcca gacttaaatt tctaccttaa agtcttgagc atg act gtt cag qaa 115 Met Thr Val Gin Glu 1 ttc gac cgc gcg acc aaa ccc aca cca aaa ccc cca att gtt tct tgg 163 Phe Asp Arq Ala Thr Lys Pro Thr Pro Lys Pro Pro Ile Val Ser Trp 15 gcg ttt tgg gat tgg ggt tcc gcc tct ttc aac gcg gtc ctc gtg acc: 211 WO 01/00804 WO 0114i804PCT/IBOO/00922 Ala Phe Trp Asp Trp Gly Ser Ala Ser Phe Asn Ala Val Leu Val Thr 30 ttt att Phe Ile gag ggt Glu Gly ggC gte Gly Val ate aag Ilie Lys gtg ttc Val Phe ttt ttc Phe Phe gag ttc Giu Phe 135 cgc gaa Arg Giu 150 tte ggt Phe Gly ggt gat Gly Asp atg aat Met Asn tet gcg Ser Ala 215 get gcc Ala Ala 230 ttc Phe tee Ser att Ile Gly t tg Leu tgg Trp 120 get Ala aac As n ggc Gly gge Gi y atc Ile 200 att Ilie gaa Giu t eq Ser aac Asn gtt Val act Thr at g Met 105 ttt Phe gaa Glu gtg Val1 atc Ile gat Asp 185 ege Arg ceg Pro gac Asp gte ValI gc Al a g cg Ala cgc Arg ttt Phe ggt Gly gtt Val1 Gly gtt Val1 170 ace Thr etc Leu gca Al a cac His tat T yr aca Thr gt t Val1 75 ege Arg tgt Cys gta Val cag Gin ega Arg 155 eta Leu eg e Arg gte Val1 ett Leu ec Pro 235 ct e Leu tea 5er 60 gt t Val1 agg Arg etc Leu gee Ala t ac Tyr 140 gt t Val1 et g Leu gga Gly gea Ala ett Leu 220 aaa Lys act Thr 45 ctg Leu gee Ala tea S er ttt Phe ate Ile 125 tat Tyr t ct Ser ctt Leu tte Phe gtg Val1 205 ega Arg ggc Gly ga t Asp tat Tyr ca Pro etg Le u aca Thr 110 atg Met geg Ala ggt Gly gt t Val1 eta Leu 190 ctt Leu gte Val1 etc Leu tea Ser teg Ser gte Val ege Arg 95 gta Val 9gg Ala eag Gin ttc Phe tgt Cys 175 aac Asn gea Ala eea Pro a ta Ile gte ValI atg Met atg Met 80 atg Met aag Lys ate Ilie etc Leu 9ge Gi y 160 tac Tyr etg Leu gee Ala gaa Glu get Ala 240 gge Gly geg Ala gge Gi y tgg Trp aae As n gee Ala tee Ser 145 t gg Trp eta Leu ec Pro gtt Val1 att Ile 225 gee Al a gee ace Ala Thr gte gee Val Ala agg ega Arg Arg aea ett Thr Leu act gat Thr Asp 115 aae ate Asn Ile 130 eaa ate Gin Ile tee atg Ser Met ggt ttt Gly Phe ate gaa Ile Giu 195 tgg tte Trp Phe 210 gag gea Glu Ala tac aag Tyr Lys etc Leu ate Ile tea Ser gte Val 100 ccc Pro ace Thr teg Ser ggt Gi y gt t Val1 180 ga e Asp ttg Leu cag Gin gat Asp ccc Pro get Ala ga t Asp ac Thr aca Thr ttt Phe ace Thr tac Tyr 165 gee Al a gge Gly gte Val1 gt a Val1 etc Leu 245 259 307 355 403 451 499 547 595 643 691 739 787 835 ttt ggg Phe Gly tt g ag ate get gag ctg tgg aaa eaa hGyGin Ile Ala Giu Leu Trp Lys Gin ege aae tee Arg Asn Ser gtg tat Val Tyr WO 01/00804 WO 0100804PCT/IBOO/00922 ttC Phe acc Thr gat Asp gca Ala 310 atc Ile ttc Phe gcg Ala ctt Leu acc Thr 390 gtg Val1 att Ile ctc Leu ttc Phe gtc Val1 295 ct C Leu tt g Leu gtt ValI t tt Phe tcc Ser 375 ggc GI y Gi y ctg Leu 250 atc gca gca act Sle Ala Ala Thr 265 *gqt gCC atc ctt Gly Ala Ile Leu 280 ctc: ctc ttc ggt Leu Leu Phe Gly ctc gga gga ttc Leu Gly Gly Phe 315 att tct ctt gcc Ile Ser Leu Ala 330 gaa ggc ccc act Giu Gly Pro Thr 345 gtg gga cct gca Val Gly Pro Ala 360 cca gat ggc cag Pro Asp Gly Gin cgt gcc gtg agi Arg Ala Val Ser 395 ctc acc ggc gat Leu Thr Giy A-sp 410 cta ttc ggt att Leu Phe Gly Ile gt t Val1 gcq Ala qtc Val1 300 cta Leu atc Ile aat Asn cag Gin ga a Glu 380 t gg Trp gac Asp gtg lal 255 ttc cgt gac Phe Arg Asp 270 gtc tct gtg Val Ser Val 285 gca gcc aac Ala Ala Asn gac gat cgc Asp Asp Arg atg atc gcc Met Ile Ala 335 ttc tgg atc Phe Trp Ile 350 tca gcg tcg Ser Ala Ser 365 ggc cag ctc Gly Gin Leu atg gtg ccg Met Val Pro cgc act ggt Arg Thr Gly 415 ctg ctg agc gga Gly tac Tyr gtg Val1 gt C Vali 320 gat Asp ttc Phe aga Arg ttc Phe t cg Ser 400 att Ile ctc Leu gga Gly gtc Val 305 ggg Gly gct Aia gga Gi y agc Ser ggc Gly 385 ctg Leu ttg Leu gcC Al a cta Leu 290 t ct Ser cca Pro gca Al a tta Leu tat Tyr 370 ctt Leu ttt Phe gcC Dila gga Gly 275 tct Ser 9 cg Ala aaa Lys att Ile atc Ile 355 tta Leu tat Tyr ggt Gly atc Ile 260 gt a Val gcc Ala ttg Leu ccc Pro ctc Leu 340 ctc Leu aca Thr gcc Al a gta ValI gcg Ala 420 ttt Phe ggt Gly gga Gly atc Ile 325 ttc Phe tgt Cys cgt Arg act Thr ttt Phe 405 ctg Leu 931 979 1027 1075 1123 1171 1219 1267 1315 1363 1411 1443 atg gtg aag cca ccg cac Leu Leu Ser Met Val Lys Pro Pro His 430 435 425 aag gtg aag tag~ Lys Val Lys 440 ,caaagc gcccacaagg att <210> 268 <211> 440 <212> PRT <213> Corynebacterium giutamicum <400> 268 WO 01/00804 Met Thr Val Gin Glu Phe Asp Arg Ala Thr Lys Pro Thr Pro 1 5 10 PCT/1B00100922 Lys Pro Pro Ala Gly Ala Gly Trp Asn Ala Ser 145 Trp Leo Pro Val Ile 225 Ala Arg Ile Val Ala Va1 Arg Thr Thr Asn 130 Gin Ser Gly Ile rrp 210 lu ryr sn Val Leu Thr Ala Arg Leu Asp 115 Ile Ile Met Phe Glu 195 Phe Ala Lys Ser Ser Trp Ala Phe 2( Va] LeL Ile Ser Va1 100 Pro Thr Ser Gly Va1 180 Asp Leu Gln Nsp lal 0 L Thr Pro Ala Asp Thr Thr Phe Thr Tyr 165 Ala Gly Val Val Leu 245 Tyr I Phe Glu Gly 70 Ile Val Phe GIu Arg 150 Phe Gly Met Ser Ala 230 ?he ?he Ile Gly 55 Val Lys Phe Phe Phe 135 Glu Gly Asp Asn Ala 215 Ala Gly Leu I TrF Phe 4C Ser Ile Gly Leu Trp 120 Ala Asn Gly Gly Ile 200 Ile lu 31n Asr Sez Asr Val Thr Met 105 Phe Glu Va1 Ile Asp 185 Arg Pro Asp Ile Trp Gly Ser Val Tyr Leu Ala Thr Ser Ala Val Val 75 Arg Arg Arg 90 Phe Cys Leo Gly Val Ala Val Gin Tyr 140 Gly Arg Val 155 Val Leo Leo 170 Thr Arg Gly Leu Val Ala Ala Leu Leo 220 His Pro Lys 235 Ala Glu Leu 250 Ala Thr Val Ile Leu Ala Ala Thr Leu Ala Ser Phe Ile 125 Tyr Ser Leu Phe Val 205 Arg Gly Trp Phe lal 285 Ser Asp Tyr Pro Leu Thr 110 Met Ala Gly Val Leu 190 Leu Va1 Leo Lys Arg 270 Ser Phe Ser Ser Val Arg Val Ala Gin Phe Cys 175 Asn Ala Pro Ile Gin 255 Asp Val Asn Val Met Met Met Lys Ile Leu Gly 160 Tyr Leu Ala Glu Ala 240 Asp Gly Tyr Ala 265 Ala Leo Ala Gly 275 V4l Phe Thr Phe 280 Gly Leo 290 Ser Ala Gly Asp Leo Leo Phe Gly Ala Ala Asn Val Val1 305 Gly Ala Gly Ser Gi y 385 Leu Leu Val WO 01/00804 Ser Ala Leu Pro Lys Pro Ala Ile Leu 340 Leu Ilie Leu 355 Tyr Leu Thr 370 Leu Tyr Ala Phe Gly Val 1 Ala Ilie Ala 1 420 Lys Pro Pro 435 PCT/IBOO/00922 Ala 310 Ile Phe Ala Leu Thr 390 Val Ile Lys Leu Leu Leu Ile Val. Giu Phe Val 360 Ser Pro 375 Gly Arg Gly Leu Leu Leu Val Lys 440 Gly Ser Gly 345 Gi y Asp Al a Thr Phe 425 <210> 269 <211> 840 <212> DNA <213> Corynebacterium giutamicum <22 0> <221> CDS <222> (101)..(817) <223> RXN00535 <400> 269 aatcgcatgg ggcaccgtqq tcagacaccg gatcgcgctc cctaaggagc tcacctttac tcaatgctct gatgacaccg atg agt acc gcg atg ctg gca tat ttc tta caa Met Ser Thr Ala Met Leu Ala Tyr Phe Leu Gin 15 ttc ggc acc ctc ttg gta gtg caa cca gtg ctt Phe Gly Thr Leu Leu Val Val Gin Pro Val Leu 30 ttc acg ctg ccg ctc tca gca cga ttc aat ggc Phe Thr Leu Pro Leu Ser Ala Arg Phe Asn Gly 45 cgcaccccaa aagatggctc atg tgg tgg gca ggc Met Trp Trp Ala Giy 1 aca gta gca ctt ggt Thr Val. Ala Leu Gly gtc ctg tcg ctg atg Val. Leu Ser Leu Met tac cga cta cgc cga Tyr Arg Leu Arg Arg wo 01/00804 WO 0100804PCT/IBOO/00922 act gaa atc ttc tgg gct acc ctc ctc Thr Giu Ilie Phe Trp Ala Thr Leu Leu atc Ile cga Arg t gq T rp ggt Gly gcc Ala aac Asn 150 gt g Val1 gcc Al1 a gtt Val1 9gc Gi y ttg Leu att Ile ctt Leu gtg Val1 120 gtg Val1 gaa Giu cag Gin acc Th r ggC Gi y 200 gca Al a gga Gi y cca Pro gcg Ala 105 acg Thr gat Asp 9gC Gi y tat Tyr att Ile 185 gaa Giu cta Leu cgc Arg gt a Val1 ga a Giu ggt Gly ct t Leu tac Tyr tcc Se r 170 gcc Ala aaa Lys ctg Leu ccc Pro 75 ct t Leu tac Tyr gca Ala tt t Phe 9qc Gi y 155 ttt Phe gaa Glu ttc Phe gtg Val1 ct t Leu tta Leu gt a Val1 ttg Leu gt c ValI 140 cta Leu aac Asn c ca Pro caa Gin atg Met 220
CCC
Pro gtc Val tta Leu ttt Phe 125 cat His atc Ile gct Al a att Ile gtc Val 205 att Ile g ga Gly qgc Gly aag Lys 110 ggc- Gi y caa Gin ctc Leu ggc Gly gtt Val1 190 gtg Vai gtt Val1 acc gta gcc Thr Val Ala aac ccc cac Asn Pro His 80 gtt gca gta Vai Ala Vai aag gac aaa Lys Asp Lys tac gta gca Tyr Vai Ala ggc ata acg Gly Ile Thr 145 acc gca tta Thr Ala Leu 160 gaa cta caa Giu Leu Gin 175 gcc ttc agt Ala Phe Ser gac tgg gaa Asp Trp Giu tcc acc att Ser Thr Ile 99r gtg ValI ccc Pro a tg Met gcc Ala gtg Val 130 gga Gi y ct t Leu aaa Lys ttg Leu tgg Trp 210 gca ggC Gly c ca Pro gg t Gly ct c Leu 115 atg Met ct c Leu gga Giy t cg Ser ggc Gly 195 atc Ile ctg atg Met gat Asp a tg Met ctt Leu aaa Lys ttg Leu atc Ile 165 ccc Pro ttg Leu at g Met cgt Ala Leu Ser Arg aca agc aca atg ccg gcc Thr Ser Thr Met Pro Ala tcg aaa agg taaaactcca aagttccccc Ser Lys Arg 230 235 cga <210> 270 <211> 239 <212> PRT <213> Corynebacterium glutamicum <400> 270 WO 01/00804 met Trp Trp Ala Gly Met Ser Thr Ala Met Leu Ala Tyr Phe 1 5 10 PCT/IBOO/00922 Leu Gin Thr Val Tyr Ala His Val Lys Ala Thr 145 Leu Gln Val1 Leu Arg Val Pro Met Al a Val 130 Gly Le u Lys Al a Ser Leu Giy Pro Gly Leu 115 Met Leu Gi y Ser Leu Leu Arg Ile Leu Gly 100 Ile Ser Ile Thr Leu 180 Giy Met Arg Met Asp Met Leu Lys Leu Ile 165 Pro Phe Phe Thr Ile 70 Arg Trp Gly Ala Asn 150 ValI Al a Val1 Gly Thr Glu 55 Val1 Trp Leu Leu Ala 135 Trp Gin Met Leu Thr Leu 40 Ile Leu Ile Leu Val1 120 Val1 Glu Gin Thr Gly 200 Al a Leu 25 Pro Phe Gly Pro Al a 105 Th r Asp Gly Tyr Ile 185 Gi u Leu Leu Leu Trp Arg Va 1 90 Giu Gly Leu Tyr Ser 170 Al a Lys Leu Val Se r Al a Pro 75 Leu Tyr Ala Phe GI y 155 Phe Glu Phe Val1 Al a Thr Leu Leu Val Leu Val1 140 Leu Asn Pro Gin Gin Arg Leu Pro Val1 Leu Phe 125 His Ile Ala Ile Val1 205 Pro Val Phe Asn Leu Thr Gly Asn Gly Val Lys Lys 110 Gly Tyr Gin Gly Leu Thr Giy Glu 175 Val Ala 190 Val Asp Leu Gly Val Pro Ala Asp Val1 Ile Al a 160 Leu Phe Trp Ser Leu Gly Tyr Leu 195 Glu Trp 210 Ile Ala Met Gly Ile 215 Val Met Ile Val Ser Thr 220 Ile Ala Leu Ser Arg Thr Ser Thr Met Pro 225 230 <210> 271 <211> 2472 <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> (2449) <223> RXN00453 <400> 271 Gly Ser Lys Arg WO 01/00804 tagtggggcg tgaaaaaata gctcatttaa gaggagaagc PCT/IBOO/00922 aaccccgtgg cgaaattgct attcaggttg gggcgatggt cctataatcg caagtggatt gtg att tcg gca. tgg ct a Leu ggg Gly act Thr gcc Ala ga t Asp gag Glu gt t Val agc Ser qg Ala gat Asp 150 aac As n ggt Gly ct t Leu ttc Phe gtt Val1 gcc Ala ga t Asp gac Asp gag Glu atg Met gtg Val1 135 gt t Val gaa Giu gga Gly att Ile agt Ser t ct Ser gga Gly cct Pro aat Asn gtg Val ggg Gly 120 ttg Leu gag Glu gcg A~la cct Pro ttg Leu aac As n ct g Leu gtt Val cag Gin ttg Leu tct Ser 105 ctt Leu agc Ser gcc Al a atg Met gc t Ala 185 pgcc Al tct Sex gt t ValI aac Asn atg Met cct Pro cct Pro cct Pro ga a Gi u qca Ala caa Gln 170 ttc Phe att Ile ttc Phe *gaa *Glu gtg Val atg Met 75 gat Asp gcg Ala gag Gi u ga c Asp gaa Giu 155 atc Ile ggt Gly I gtt Val1 act Thr aa t Asn gt t Val1 60 act Thr ttt Phe ttg Leu ga a Gl u aaa Lys 140 tat ryr ggt Gly la t isp gg t att t tc Phe 45 ttc Phe gcg Al a ggt Gl y gaa Glu acc Thr 125 acc Thr gtg Val1 ga a Glu cca Pro *ggt Gly *gaa Glu 30 cct Pro caa Gin atg Met ggg Giy gag Glu 110 gct Ala att Ile gag Giu gat Asp att Ile 190 ctg Leu gac Asp ga t Asp tcc Se r gat Asp gga Gly 95 atg Met gca Ala 99C Gi y caa Gin tta Leu 175 -ag 31 n gcc Ala acc Thr ca g Gin ccg Pro gca Ala 80 gag Glu gt c Val1 aag Lys tac Tyr aaa Lys 160 ggt Gi y att Ile Val1 1 ctg Leu cct Pro a cg Thr gaa Giu gtc Val1 cgc Arg at c Ile gat Asp.
acc Thr 145 cac His gtc Val gaa Glu Ile acg Thr tcg Ser aac As n gga Gi y gt t Val1 ttc Phe gag Glu gct Ala 130 t ct Ser :gc Arg krg Icc ['hr Ser atg Met att Ile ccg Pro a cc Thr gat Asp ggc Gly cag Gin 115 gcc Ala ttc Phe ga t Asp gtg Val acc Thr 195 Ala cag Gin ga t Asp gtg ValI aeg Thr tac Tyr aat Asn 100 aig Met aat Asn aac Asn gt g Val1 gaa Glu 180 agt Ser Trp aag Lys gcc Ala acg Thr ctt Leu att Ile cct Pro acc Thr ct g Leu att Ile atc Ile 165 gcc Al a gag Glu 115 163 211 259 307 355 403 451 499 547 595 643 691 atc atc ggt Ile Ile Gly 200 att ggc atc gcg Ile Gly Ile Ala atc gtg ttg att Ilie Val Leu Ile t tc Phe 210 acc ttt ggt Thr Phe Gly WO 01/00804 PCT/1B00/00922 tct ttg att gct gca. ggc ttg cct ttg att acc gcg gtg atc ggc gtg 787 Ser ggc Gly 230 aac Asn att Ile cg c Arg ag t Se r ctc Leu 310 gcg Ala gcg Al a gga Gly aat Asn ccg Pro 390 Leu 215 att Ile aat Asn gac Asp atg Met gcg Al a 295 atc Ile ttt Phe ct g Leu at t Ile cgt Arg 375 gg t Gly Ile ggt Gly gt g Val tac Tyr cca.
Pro 280 gtg Val att Ile a cg Tb r t tg Leu ggt Gly 360 cgt Arg ctt Leu Ala gcj Ala~ act Th r qc9 Ala 265 cgt Arg gt g Val1 gcg Al a gtg Val1 ggt Gly 345 gga Gly tcc Se r gtg ValI Ala Gly Leu Pro Leu Ile Thr Ala Val Ile Gly Val 220 225 ctg Leu cca.
Pro 250 ctg Leu gcc Ala ttt Phe gat Asp ttc Phe 330 gtg Val1 aac As n aag Lys gtg Val1 gc~ Ali 23! gtc Val ttt Phe gat Asp gct Ala atc Ile 315 qtg Val ttt Phe cc a Pro ggt Gly gca.
Ala 395 i att Ile ctc -Leu *att Sle *gct Ala ggc Gly 300 gga Gly gct Ala ggt Gi y acg Thr cgc Arg 380 gtg Val cag Gin gt Va gc Ali t tq Le.
gcc Ala 285 gcg Al a ttc Phe gtg Val ggt Gly c ca Pro 365 tca Se r gtg ValI L tg Leu I ctg LLeu gtg Val tct Ser 270 gga.
Gly acg Thr ctc Leu ctc Leu cat His 350 aag Lys tgg Trp gtc Val tca Ser gcc Ala atg Met 255 agg Arg a ig Met gtg Val1 a cg Tb r att Ile 335 gcg Ala cag Gln gtc Val1 t tg Leu ct g Leu 415 acg Thr 240 att Ile tac T yr gcg Ala att Ile gcc Al a 320 gcg Al a ttc Phe acg Thr aag Lys gg t GI y 400 cct Pro gcg *Ala *Gly cgt Arg gtg Val atc Ile 305 atg Met t tg Leu aag Lys tgg Trp ctt Leu 385 ctt Leu tct Ser ttt Phe ctg Leu gcg Ala ggC Gi y 290 gcg Al a ggt Gly a cg Thr 9gC Gly gag Glu 370 gt a Val1 gt Gi y gac Asp act Thr gcc Ala gag Giu 275 aca, Thr ct g Leu att Ile ttt Phe aag Lys 355 caa Gin cag Gin gcc Ala t cc Ser ga t Asp gtg Val1 260 tat Tyr gct Ala gta Val t ct Ser at c Ile 340 atc I le gcg Ala aaa Lys t tg Leu acc Thr 420 ctc Leu 245 ggc Gly aag Lys ggt Gly gcc Al a gcg Ala 325 ccg Pro cct Pro ctt Leu gca Ala acc Tb r 405 tcc Se r 835 883 931 979 1027 1075 1123 1171 1219 1267 1315 1363 1411 att cct gca. atg aac ctg Ile Pro Ala Met Asn Leu 410 aat att gat acc act cag cgt cag tcg gct gat ttg atg gca gag ggc Asn Ile Asp Thr Gln Arg Gln Ala Asp Leu Met Glu Gly WO 01/00804 WO 0100804PCT/IBOO/00922 ttt ggc gcg Phe Gly Ala ggc qtt aat gcg ccg ttc ttg Gly Val Asn Ala Pro Phe Leu gtc atc gtc gat acg cat Val Ile Val Asp Thr His gag gtc Glu Val 455 gag cct Glu Pro 470 acc tat Thr Tyr aat gcg Asn Ala ctc gtg Leu Val atg cac Met His 535 act gaa Thr Glu 550 gag cag Glu Gin ttg gct Leu Ala ctg gtt Leu Val gcg acg Ala Thr 615 cct ggt Pro Gly 630 ttc ggt Phe Gly 440 aat Asn ga a Glu atg Met cag Gln act Thr 520 gt g Val ctg Leu ctg Leu att Ile gct Ala 600 gtg Val1 ccg Pro t tg Leu gct Ala gag Glu tat Tyr at c Ile 505 c ca Pro ct g Leu ggt Gly gaa GI u ttc Phe 585 ggc Gi y t tg Leu ctg Leu g cc Al a ga t Asp goc Gly gtc Val1 490 atc Ile t ac T yr cgt Arg acc Thr gac Asp 570 ctc Leu ctt Leu gtc Val att Ile atg Met2 650 t cc Ser gag Giu 475 acc Thr agc Ser acc Thr gcg Ala act Thr 555 gca Al a ctc Leu 9gc Gly t gg Trp tcc Ser 635 gac ksp acc Thr 460 ttc Phe ca g Gin gt c Val gga Gly cag Gin 540 ggg Gly at g Met att Ile ttc Phe cag Gin 620 ttc Phe tat Tyr qca Ala gat Asp acc Thr aat Asn cct Pro 525 gaa Glu tt t Phe ccg Pro ctg Leu ttg Leu 605 gag Giu atg Met cag Gin t to Leu cgg Arg t ac Tyr ga t Asp 510 gcg Al a gct Al a a cg Thr gtt Val gtg Val 590 ttg Leu goC GI y ccg Pro gtg Val1 cag Gin gag Giu aat Asn 495 gat Asp gat Asp cag Gln gcg Ala t ac Tyr 575 ttc Phe tct Se r ttc Phe atc Ile t tc Phe 655 cca Pro cag Gin 480 t cc Ser t tc Phe aaa Lys att Ile Ott Val 560 ctc Leu cgt Arg gtg Val1 ggt Gi y ttc Phe 640 ctt Leu ct g Leu 465 gcg Al a aac Asn act Thr gag Glu gag Glu 545 cag Gin gct Al a tcc Se r gt Gly goc Gly 625 ctc Leu gtg Val att gag gca cag Ile Glu Ala Gin gct Ala atc Ile gcg Ala acc Th r 530 ga t Asp ttg Leu o to Val1 ctg Leu gcg Ala 610 t tt Phe atc Ile act Thr 1459 1507 1555 1603 1651 1699 1747 1795 1843 1891 1939 1987 2035 2083 2131 gag cac tac acc cac cac aat ggc aag gga cag cct ggt tcc aag tac WO 01/00804 WO 0100804PCTfIBOO/00922 Giu His Tyr Thr His His Asn Giy Lys Gly Gin Pro Gly Ser Lys Tyr 675 665 670 acc ccg gtt gag cag tca gtg att gaa Thr Pro Val Giu Gin Ser Val Ile Giu 680 685 gtg gtt aca gca gcg gca ctg atc atg Val Val Thr Ala Ala Ala Leu Ile Met 695 700 att gat cag ccg ttg cca ttt att aag Ile Asp Gin Pro Leu Pro Phe Ile Lys 710 715 gcg ggc gtq ttt ttc gat gct ttc ttc Ala Giy Val Phe Phe Asp Ala Phe Phe 730 gcg tcg atg ttc ctg atg qgc aag gcc Aia Ser Met Phe Leu Met Gly Lys Ala 745 750 ctg gat cga att ctg cca agt ttg gac Leu Asp Arg Ilie Leu Pro Ser Leu Asp 760 765 aag gaa tgg gag gag aag cag gct gca Lys Giu Trp Glu Giu Lys Gin Ala Ala 775 780 gat <210> 272 <211> 783 <212> PRT <213> Corynebacterium giutamicum <400> 272 Val Ilie Ser Ala Trp Leu Leu Ile Leu 1 5 Leu Thr Met Gin Lys Gly Phe Ser Asn 25 Pro Ser Ile Asp Ala Thr Vai Ser Leu Thr Asn Pro Val Thr Ala Ala Gly Val Giu Gly Thr Thr Leu Asp Asp Pro Gin 70 Val Val Asp Tyr Ile Giu Asp Aso Leu ggc Gly att Ile atc Ile att Ile 735 acg Thr att Ile cgt Arg ttc acg cag ggc tcc cgc Phe Thr Gin Gly Ser Arg 690 gcc gtg ttc gtg gcg ttt Ala Val Phe Val Ala Phe 705 ttc ggt ttc gcq ttg ggt Phe Gly Phe Ala Leu Gly 720 725 cgc atg ggt ctq gtc ccc Arg Met Gly Leu Val Pro 740 tgg tgg atg cct aag tgg Trp Trp Met Pro Lys Trp 755 gaa ggc acc gca ctg gag Giu Gly Thr Ala Leu Giu 770 tagacttggc acctatgtca 2179 2227 2275 2323 2371 2419 2469 2472 Ala Ile Ser Phe Val Glu Asn Val Met Met Pro Asp Gly Giu Pro Gin Met Gi y WO 01/00804 PCT/IB00/00922 Arg Phe Gly Asn Pro Val Glu Val Ser Pro Ala Leu Glu Glu Met Val Ile Asp Thr 145 His Val Glu Ile Ala 225 Ala Gly Arg Val Ile 305 Met Leu Lys Glu Ala 130 Ser Arg Arg Thr Phe 210 Val Phe Leu Ala Gly 290 Ala Gly Thr Gly Gin 115 Ala Phe Asp Val Thr 195 Thr Ile Thr Ala Glu 275 Thr Leu Ile Phe Lys 355 100 Met Asn Asn Val Glu 180 Ser Phe Gly Asp Val 260 Tyr Ala Val Ser Ile 340 Ile 105 110 Thr Leu Ile Ile 165 Ala Glu Gly Val Leu 245 Gly Lys Gly Ala Ala 325 Pro Pro Ser SAla Asp 150 Asn Gly Ile Ser Gly 230 Asn Ile Arg Ser Leu 310 Ala Ala Gly r Met SVal 135 Val Glu Gly Ile Leu 215 Ile Asn Asp Met Ala 295 Ile Phe Leu Ile Arg 375 Gly 120 Leu Glu Ala Pro Gly 200 Ile Gly Val Tyr Pro 280 Val Ile Thr Leu Gly 360 Arg Leu Ser Ala Met Ala 185 Ile Ala Ala Thr Ala 265 Arg Val Ala Val Gly 345 Gly Ser Pro Glu Ala Gin 170 Phe Gly Ala Leu Pro 250 Leu Ala Phe Asp Phe 330 Val Asn Lys Glu Asp Glu 155 Ile Gly Ile Gly Ala 235 Val Phe Asp Ala Ile 315 Val Phe Pro Gly Glu Lys 140 STyr Gly Asp Ala Leu 220 Ile Leu Ile Ala Gly 300 Gly Ala Gly Thr Arg 380 Thr 125 Thr Val Glu Pro Phe 205 Pro Val Ala Leu Ala 285 Ala Phe Val Gly Pro 365 Ser Ala Ile Glu Asp Ile 190 Ile Leu Leu Val Ser 270 Gly Thr Leu Leu His 350 Lys Trp Ala Gly Gin Leu 175 Gin Val Ile Ala Met 255 Arg Met Val Thr Ile 335 Ala Gin Val Lys Tyr Lys 160 Gly Ile Leu Thr Thr 240 Ile Tyr Ala Ile Ala 320 Ala Phe Thr Lys Trp Glu Gin Ala Leu Asn 370 Val Gin Lys Ala Gly Leu Val Val Val Val Val Leu Leu Ser Leu Ile Leu 465 Ala Asn Thr Glu Glu 545 Gin Ala Ser Gly Gly 625 Leu Val WO 01/00804 Gly Ala Leu Asp Ser Thr 420 Met Ala Glu 435 Val Asp Thr 450 Ile Giu Ala Ala Arg Phe 2 Ile Asp Val I 500 Ala Ala Gin 1 515 Thr Pro Glu L 530 Asp Val Thr G Leu Asp Ile T Val Val Vai G 580 Leu Leu Val P 595 Ala Ala Phe G 610 Phe Val Asn T Ile Gly Val TI 6' Thr Arg Met A~ 660 PCT/IBOO/00922 Thr 405 Ser ly His 3in kla 185 .ys :le ,eu ;ly 'hr 65 ly ro ly hr hr 45 rg Ile Asn Phe Glu Glu 470 Thr Asn Leu Met Thr 550 Glu Leu Leu Ala Pro 630 Phe C Glu H Pro Ile Gly Val 455 Pro Tyr Ala Val His 535 Glu Gin Ala Val rhr 515 3ly 'ly 'is Al As; Alz 44C Asr Glu Met Gin Thr 520 Va1 Leu Leu Ile Ala 600 Val Pro Leu Tyr i Met Thr 425 Gly Ala Glu Tyr Ile 505 Pro Leu Gly Glu Phe 585 Gly Leu Leu Ala I Thr I 665 Asr 410 Thi Val AsF Gly Val 490 Ile Tyr Arg Thr Asp 570 Leu Leu Val Ile Met 650 iis Leu Gin Asn Ser Glu 475 Thr Ser Thr Ala Thr 555 Ala Leu Gly Trp Ser 635 Asp His Gir Arg Ala Thr 460 Phe Gin Val Gly Gin 540 Gly Met lie Phe Gin 620 Phe Tyr Asn Leo Gin Pro 445 Ala Asp Thr Asn Pro 525 Glu Phe Pro Leu Leu 605 Glu Met Gin Gly Ile Ser Ser 430 Phe Leu Arg Tyr Asp 510 Ala Ala Thr Val Val 590 Leu Gly Pro Val Lys 570 ;lu Leu 415 Ala Leu Gin Glu Asn 495 Asp Asp Gin Ala Tyr 575 Phe Ser Phe Ile Phe 655 Gly Gly Pro Asp Val Pro Gin 480 Ser Phe Lys Ile Val 560 Leo Arg Val Gly Phe 640 Leu Sin Phe Pro Gly Ser Lys Tyr Thr Pro Val Glu Gin Ser Vai 675 680 685 Ile Met Ile Ala Thr Gin 690 Gly Ser Arg Val Va1 695 Thr Ala Ala Ala Leu 700 WO 01/00804 Val Phe Val Ala 705 Gly Phe Ala Leu Met Gly Leu Val 740 Trp Met Pro Lys 755 Gly Thr Ala Leu 770 <210> 273 <211) 597 <212> DNA <213> Corynebact<20 <221> CDS <222> (57 <223> RXN00932 <400> 273 cccaattaat ttatg aataaggtga tgttt PCT/IBOO/00922 Phe Ile Asp Gin Pro Leu Pro Phe Ile Lys Ile Phe 710 715 720 Giy Ala Gly Val Phe Phe Asp Ala Phe Phe Ile Arg 725 730 735 Pro Ala Ser Met Phe Leu Met Gly Lys Ala Thr Trp 745 750 Trp Leu Asp Arg Ile Leu Pro Ser Leu Asp Ile Giu 760 765 Giu Lys Giu Trp Giu Giu Lys Gin Ala Ala Arg 775 780 erium giutamicum '4) rcactt. cggtgaggtt actcacaaag agtagcgtgc aaagcccagc caacg attaggttac ggtaggggcc atg acg cca cag aaa Met Thr Pro Gin Lys 1 gca gcc ctt tta gaa atg ggt acc tgg acc ctg ctg Ala Ala Leu Leu Giu Met Gly Thr Trp Thr Leu Leu 15 atc tta aaa tac agt gga gtg aca gac gcc gta ace Ilie Leu Lys Tyr Ser Gly Val Thr Asp Ala Vai Thr 30 ggt atc cac ggc ttt ggc ttc ctc tgt ttt gca gcc Gly Ile His Giy Phe Gly Phe Leu Cys Phe Ala Ala gtg tgg ate aat aat aag tgg aca ttc ccg cag ggt Vai Trp Ile Asn Asn Lys Trp Thr Phe Pro Gin Gly atc gtc tct gtt atc ecg tgg gct gca ttg cca ttt Ile Val Ser Val Ile Pro Trp Ala Ala Leu Pro Phe 75 80 gac aag aag ggc ctc gtt gcc ggc gga tgg cgc ttt Nsp Lys Lys Gly Leu Val Ala Gly Gly Trp Arg Phe 95 100 ctt Le u ate Ile cct Pro ate Ile atc Ile gca Al a ttt Phe atg Met ggc Gly acc Thr ttg Leu gca Al a 115 163 211 259 307 355 403 WO 01/00804 tea gat ccg tee qaa aag cca cac act ttc Ser Asp Pro Ser Giu Lys Pro His Thr Phe 105 110 caa ttg gtc agg cac cca atc cga tec att Gin Leu Val Arg His Pro Ile Arg Ser Ile 120 125 atc gcc gte gtc ttc tct atc ttq ctg gcg Ile Ala Val Val Phe Ser Ile Leu Leu Ala 135 140 cca gat gce ate gea aac act gtg gat taa Pro Asp Ala Ilie Ala Asn Thr Val Asp 150 155 atg '210> 274 <211> 158 <212> PRT <213> Corynebacterium giutamicum <400> 274 Met Thr Pro Gin Lys Leu His Arg Phe Ala 1 5 10 Thr Trp Thr Leu Leu Ilie Ilie Gly Met Ilie 25 Thr Asp Aia Vai Thr Pro Ile Ala Gly Giy 40 Leu Cys Phe Ala Ala le Thr Ile Thr Vai Thr Phe Pro Gin Gly Ile Ala Giy Leu Ile 70 Ala Ala Leu Pro Phe Ala Leu Trp Ala Asp 90 Gly Gly Trp Arg Phe Ser Asp Pro Ser Giu 100 105 Asp Lys Ile Leu Ala Gin Leu Val Arg His 115 120 Ile Leu Leu Val Ilie Ile Ala Val Val Phe 130 135 Gly Pro Pro Tyr Asp Pro Asp Ala Ilie Ala 145 150 ttt gac aag ate ttg get Phe Asp Lys Ile Leu Ala 115 tta att etg etg gtg att Leu Ile Leu Leu Val Ile 130 atg gga cca eet tat gat Met Gly Pro Pro Tyr Asp 145 acaacag eetcctteae PCT/IBOO/00922 451 499 547 594 Ala Leu Ile Trp ValI Lys Lys Pro Ser Asn 155 Leu Tyr Gly Asn ValI Gly His Arg 125 Leu Val1 Giu Se r Phe Asn Ile Leu Thr 110 Ser Leu Asp Met Gi y Gly Lys Pro Val Phe Ile Ala WO 01/00804 <210> 275 <211> 534 <212> DNA <213> Corynebacteriumr glutaznicum <220> <221> CDS <222> (511) <223> R~XN03022 <400> 275 acgcetgtgt catccttttc attagagtgg agaaaagcce agcagtg ate atc ace get ggc atc ttg gta gcg Val Ile Ile Thr Ala Gly Ile Leu Val Ala PCT/IBOO/00922 atacagaaag ttggcgcccg eta Leu gee Ala gte ValI ggt Gi y ate Ile ate Ile gt t Val1 aaa Lys ace Thr tee Se r act Thr gt a Val1 tee Se r ga e Asp gea Al a 115 gge Gly ge9 Al a ett Leu 9c9 Al a tte Phe act Thr gte Val 100 gca Ala aaa Lys gte Val1 tat Tyr et t Leu aag Lys tea Ser 85 gca Al a aca Thr gte Val1 gag Glu ctt Leu a ca Thr 55 tee Ser ttc Phe gee Al a ace Thr caa ace geg aec gee etc Thr Aia Thr Ala Le6 ate gte ate tee etc Ile Val Ile Ser Leu etc ttc gcc ace eca Leu Phe Ala Thr Pro gac cgt ace gge get Asp Arg Thr Gly Ala gge gea gca etc gge Gly Ala Ala Leu Giy ege gac ggc ace tee Arg Asp Gly Thr Ser tea. ctt ggc ate aae Ser Leu Gly Ile Asn 110 gca gte ctt att eca Ala Val Leu Ile Pro 125 ace ctt ect gag eca Ser Gin Thr Ser Ile Thr Leu get ate get Ala Ile Ala 145 <210> 276 <211> 149 <212> PRT gta aaa ate taaaaettea ecaggacaga taa 534 Val Lys Ilie WO 01/00804 PCT/IBOO/00922 (213> Corynebacterium glutamicum <400> 276 Val Ile Ile Thr A-la Gly Ile Leu Val Ala Thr Ala Thr Ala Leu Leu 1 5 10 Met Ile Thr Ala Val Ser Glu Ser Thr Tyr Ile Val Ile Ser Leu Ala 25 Gly Phe Ser Leu Tyr Gly Leu Gly Leu Gly Leu Phe Ala Thr Pro Val 40 Thr Asp Thr Ala Leu Gly Thr Leu Pro Lys Asp Arg Thr Gly Ala Gly 55 Ala Gly Val Phe Lys Met Ser Ser Ser Leu Gly Ala Ala Leu Gly Ile 70 75 Ala Ile Ser Thr Ser Val Phe Leu Ala Leu Arg Asp Gly Thr Ser Ile 90 Asn Ser Asp Val Ala Leu Ala Gly Thr Val Ser Leu Gly Ile Asn Val 100 105 110 Val Phe Ala Ala Thr Ala Thr Ilie Thr Ala Ala Val Leu Ilie Pro Lys 115 120 125 Ala Ala Gly Lys Val Ser Gin Thr Ser Ile Thr Leu Pro Glu Pro Ala 130 135 140 Ile Ala Val Lys Ilie 145 <210> 277 <211> 586 (212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> (101)..(586) <223> RXN03151 <400> 277 ccgaacttgg agctttgctg ttggaggcag ccaaatagt& ccaatgtaaa cgcactgggt agtatttgtt taaccatcca cctcaaggag taaaacgcac gtg ctt tcc cac atc 115 Vai Leu Ser His Ile 1 att gat gtc ctc gcc gac ccg atc gat ggc acc cca ctt gta ggc gcc 163 Ile Asp Val Leu Ala Asp Pro Ile Asp Gly Thr Pro Leu Val Gly Ala 15 gaa gat ttc tca cgg ttg gtg tct gaa tct ggq cat tcc tac gat gtt 211 Glu Asp Phe Ser Arg Leu Val Ser Glu Ser Gly His Ser Tyr Asp Val WO 01/00804 PCTIIBOO/00922 30 get egt eaa ggg tat gtc ace ctg get ggt ggc gca ggt ctg cgc tat 259 Ala Arg Gin Gly Tyr Val Thr Leu Ala Gly Gly Ala Gly Leu Arg Tyr 45 tca gge gat gat gca cag atg atc gcg gat egg qaa acc ttc ctt tet 307 Ser Gly Asp Asp Ala Gin Met Ile Ala Asp Arg Giu Thr Phe Leu Ser 60 ggc qgt cac ttc gcg ccc ttc gtg gaa get gtc acc gag cat gtt caa 355 Gly Gly His Phe Ala Pro Phe Val Glu Ala Val Thr Giu His Val Gin 75 80 gat gte gtt gac cag gca ggc ctt agc gat gac gca cag cca gtg gte 403 Asp Val Val Asp Gin Ala Gly Leu Ser Asp Asp Ala Gin Pro Val Vai 95 100 tgc gaa atc ggc gcg gga acc ggc tac tac ttg tcc cat ace ctt gat 451 Cys Glu Ile Gly Ala Gly Thr Gly Tyr Tyr Leu Ser His Thr Leu Asp 105 110 115 tct gtt gca gga tct cgc gga att gge att gac gtt tcc gtg cac gee 499 Ser Val Ala Gly Ser Arg Gly Ile Gly Ile Asp Val Ser Val His Ala 120 125 130 gca aag cgt ttg gca aag tgt cac cet cgc gte ggc gca gte ate geg 547 Ala Lys Arg Leu Ala Lys Cys His Pro Arg Val Gly Ala Val Ile Ala 135 140 145 aac gea. tgg gca ege ctg ecg att gca gat aae tee teg 586 Asn Ala Tip Ala Arg Leu Pro Ile Ala Asp Asn Ser Ser 150 155 160 <210> 278 <211> 162 <212> PRT <213> Corynebacterium glutamicui <400> 278 Val Leu Ser His Ile Ilie Asp Vai Leu Ala Asp Pro Ile Asp Gly Thr 1 5 10 Pro Leu Val Gly Ala Glu Asp Phe Ser Arg Leu Val Ser Giu Ser Gly 25 His Ser Tyr Asp Vai Ala Arg Gin Gly Tyr Val Thr Leu Ala Giy Gly 40 Ala Gly Leu Arg Tyr Ser Gly Asp Asp Ala Gin Met Ile Ala Asp Arg 55 Giu Thr Phe Leu Ser Gly Giy His Phe Ala Pro Phe Val Giu Ala Vai 70 75 Thr Glu His Val Gin Asp Val Val Asp Gin Ala Gly Leu Ser Asp Asp wo 01/00804 PCT/IBOO/00922 90 Ala Gin Pro Val Val Cys Glu Ile Gly Ala Gly Thr Gly Tyr Tyr Leu 100 105 110 Ser His Thr Let' Asp Ser Val Ala Gly Ser Arg Gly Ile Gly Ilie Asp 115 120 125 Val Ser Val His Ala Ala Lys Arg Leu Ala Lys Cys His Pro Arg Val 130 135 140 Gly Ala Val Ilie Ala Asn Ala Trp Ala Arg Leu Pro Ile Ala Asp Asn 145 150 155 160 Ser Ser <210> 279 <211> 543 <212> DNA <213> Corynebacterium giutamicum <220> <221> CDS <222> <223> RXN02832 <400> 279 cgc ggg cca gtg atg gat tat aca aat caa tca tta gta gca ttt ttc 48 Arg Gly Pro Val Met Asp Tyr Thr Asn Gin Ser Leu Val Ala Phe Phe 1 5 10 ttt aaa gca tta acg tca tat tta aag aaa cac aat tgt tta tat gtC 96 Phe Lys Ala Leu Thr Ser Tyr Let' Lys Lys His Asn Cys Leu Tyr Val 25 ctt gta gat cca tat tta att gaa aat tta cgc aat gca gac ggt gaa 144 Let' Val Asp Pro Tyr Leu Ile Glu Asn Leu Arg Asn Ala Asp Gly Giu 40 att gtt aaa tct tat gat aac cga gca ttt gtt aga aca atg gat aaa 192 Ile Val Lys Ser Tyr Asp Asn Arg Ala Phe Val Arg Thr Met Asp Lys s0 55 tta ggt tat aaa cac caa ggt ttc cct gta ggt tat gat tca atg agc 240 Leu Gly Tyr Lys His Gin Gly Phe Pro Val Gly Tyr Asp Ser Met Ser 70 75 caa atc cgt tgg ctg tca gtg tta gat tta aaa gat aag act gaa gac 288 Gin Ilie Arg Trp Let' Ser Vai Leu Asp Leu Lys Asp Lys Thr Glu Asp 90 caa ctt tta aaa gaa atg gat tat caa acg aga cgt aat att aaa aaa 336 Gin Leu Leu Lys Giu Met Asp Tyr Gin Thr Arg Arg Asn Ile Lys Lys 100 105 110 a ca Thr caa Gin aaa Lys 145 ga c Asp aaa Lys WO 01/00804 tat gat att ggt Tyr Asp Ile Gly 115 act ttt ttc gac Thr Phe Phe Asp 130 ttc cgt gag tta Phe Arg Giu Len cac gcc atg tta His Ala Met Len 165 acg ttg caa tta Thr Len Gin Leu 180 gtc aaa act Val Lys Thr 120 tta ttc cat Leu Phe His 135 cca tac ttt Pro Tyr Phe 150 aag ttg gcg Lys Len Ala aaa Lys atg Met gaa Gin tat Tyr tta acg att gat Len Thr Ile Asp 125 gag gaa aag cac Gin Gin Lys His 140 atg caa aag tta Met Gin Lys Leu 155 gat tta aac gag Asp Len Asn Gin PCT/IBOO/00922 384 432 480 528 <210> 280 <211> 181 <212> PRT <213> CorynebacteriUm glntamicum <400> 280 Arg Gly Pro Val Met Asp Tyr Thr Asn Gin Ser Len Val Ala Phe Phe 1 Phe Lys Len Val Ile Val Leu Gly Gin Ile Gin Len Thr Tyr Gin Thr 1230 Al a Asp Lys Tyr Arg Leu Asp 115 Phe Len Pro Ser Lys Trp Lys 100 Ile Phe 5 Thr Ser Tyr Tyr Len Ile Tyr Asp Asn 55 His Gin Gly 70 Len Ser Val Gin Met Asp Giy Vai Lys Asp Leu Phe 135 Leu Gin Arg Phe Len Tyr Thr 120 His Lys 25 Asn Al a Pro Asp Gin 105 Lys Met Lys Leu Phe Val Len Thr Thr Ala His Arg Val1 Gly 75 Lys Arg Len Gin Asn Asn Arg Tyr Asp Arg Thr Glu Len Asp Met Ser Thr Ile 110 Asp His Val Gin Lys Ser Asp Lys Th r Phe 140 Gin Lys Len Tyr Asp Lys 145 Phe Arg Giu Len Tyr Phe Giu Giu Met 155 WO 01/00804 Asp His Ala Met Leu Lys Leu Ala Tyr Ile Asp Leu Asn Giu Tyr Leu 165 170 175 Lys Thr Leu Gin Leu 180 <210> 281 <211> 1539 <212> DNA <213> Corynebacteriurn glutamicum <220> <221> CDS <222> (1516) <223> RXN00165 <400> 281 aaacctcccc gggcccggcg cgcgaccgtc caagatqccg gcgttggatg ccaaattat gactctcaaa gtggcgttgt cgcagcqgcc gtggagcttt gtg gcg tct get ggc Val Ala Ser Ala Gly PCTJIBOO/00922 :g atg Met aa g Lys ttc Phe aac As n cat His ttt Phe t cg Ser gtg Val1 gcg Al a gtg Val1 att Ile att Ile ttg Leu gga Gi y acg Th r ga a Glu tct ttt Ser Phe gat gag Asp Glu gcc atg Ala Met gct cgg Ala Arg cgc atg Arg Met aaa gag Lys Glu cag cgg Gin Arg 105 ttg geg Leu Ala atc Ilie get Al a ttg Leu t ac Tyr ttg Leu cgc Arg gt g Vai tcg Ser tgc Cys at Ile gcg Ala atg Met gt g Val1 act Th r ggc Gi y att Ile aat Asn 9gc Gly gtt Val 45 ttg Leu act Thr gcg Al a gat Asp att Ile 125 ggg Gi y acq Thr ctt Leu gt g Val1 ga t Asp ggt Gly ate Ile 110 tat Tyr gt g Val1 cag Gin gcg Ala cag Gin gat Asp t cg Ser acg Th r gtg Val 130 120 att aat ccg tgg ttg agt gtg gct gtg ctg att ggt gga ccg ctg ctg WO 01/00804 Ile Asn Pro Trp 135 PCTIBOO/00922 Leu Ser Val Ala Val Leu Ile 140 Gly Pro Leu Leu gtt Val1 150 gct Al a gtg Val cgc Arg cat His 99c Gi y 230 ctg Leu aca Thr t cg Ser ctc Leu gag Glu 310 act gtg gtg Val Val gct att cac cg t Arg cag Gin cgt Arg gcg Al a 215 gcc Al a caa Gin cag Gin cgc Arg ggt Gly 295 gag Glu gat cay Gin Gly cyg Arg 200 gat Asp atc Ile g9 t Gi y ttt Phe tgg Trp 280 gct Ala att Ile gag Ala Ile cay gcg Gin Ala 170 ttg aga Leu Arg 185 tac gag Tyr Glu gct gcg Ala Ala ttt gtg Phe Val cag atg Gin Met 250 ttg atc Leu Ilie 265 gca tcg Ala Ser gat ttt Asp Phe atc caa Ile Gin cag ctc Gir 1 51 gt ValI att Ile gcy Ala gaa Giu t cc Ser 235 agt Ser atg Met gcg Ala gag Gl u caa 1ln 315 Itt I gtc Val gca *Ala *ttg *Leu att Ile gct Al a 220 gcg Ala att Ile ccg Pro gag Glu aga Arg 300 ctt Leu gag t ca Sei cag Glr aa g Lys tct Ser 205 cgc Arg ttg Leu gt Gi y atg Met gcg Ala 285 gtg Val gcc kl a jta aag Lys gct Ala ggt Gly 190 ggt Gly ttg Leu ggt Gly ga t Asp acc Thr 270 t cg Ser tct Ser aaa Lys tta ccg Pro gcg Ala 175 ttg Leu gag Glu aa t Asn at t Ile ttg Leu 255 atg Met gca Ala gcg Al a ggt Gly gag tty Leu 160 gct Ala gyc Gly gct Ala ggt Gly gga Giy 240 atc Ile ct t Leu aag Lys cat His ttg Leu 320 cagt cag Gin act Thr gcy Al a tat Tyr gtc Val1 225 gca Ala acg Thr ggt GI y cgt gat Asp 305 acg rhr :tg Iaaj Lys gca Ala att Ile Arg 210 acc Thr gga Gly gt t Val1 cya Arg att Ile 290 gc9 Ala yt t Val1 cca Pro cgt Arg act Thr gtc Val 195 aag Lys ga t Asp ttt Phe gtg Val1 aat Asn 275 agg Arg gac Asp att Ile cyt Arg agt Ser 355 t cg Ser gat Asp 180 a cy Thr acg Thr gcq Ala ttg Leu gga Giy 260 gtg Val gga Gly aag Lys cga Arg act Thr 340 gtc Vial gt Gly 165 gt y Val1 gt g Val1 gt t Val gcg Ala gcg Ala 245 ctc Leu gca Al a gt g Val1 gct Ala 99c Gly 325 c9g Ary a gy Ary 595 643 691 739 787 835 883 931 979 1027 1075 1123 1171 1219 Thr Asp Glu Gin Leu Val Giu Val Leu Giu Gin Leu 330 335 ctt ttt gat caa Leu Phe Asp Gin gtg att gtg gct cct cat gcg gcg Vai Ilie Val Ala Pro His Ala Ala 345 gac: aat gtg Asp Asn Val gacaatgtgcat ccc gtg gca gag AspAsnValHis Pro Val Ala Glu gtc gcg gay aaa gcc att Val Ala Glu Lys Ala Ile gaa gtt Glu Val WO 01/ 360 00804 365 PCTIIBOO/00922 qcc tcc tgt gac gat att cca qgt ggt Ala Ser Cys Asp Asp Ile Pro Gly Giy 375 380 ggt 9ga cgg ttg ctc tcg ggt ggt cag Gly Gly Arg Leu Leu Ser Gly Gly Gin 390 395 cgg gcg att gct ttt gat cca gag gtg Arg Ala Ile Ala Phe Asp Pro Giu Val 410 acg gca qtg gat tct gtg acg gag caa Thr Ala Val Asp Ser Val Thr Glu Gin 425 430 gca cac cgt gca gga aaa gtg acc att Ala His Arg Ala Gly Lys Val Thr Ile 440 445 tgg agt gcg gtg gct gat caa cac gtt Trp Ser Ala Val Aia Asp Gin His Val 455 460 gtt atg aaa tgagtgggga gacgtcgaaa a Val Met Lys 470 282 <211> 472 <2i2> PRT <213> Corynebacterium giutamicum <400> 282 Vai Ala Ser Ala Gly Met Ala Ala Ser 1 5 Pro Val Ilie Val Gly Lys Ala Val Asp 25 Leu Gin Arg Leu Trp Phe Trp Ilie Ala 40 Thr Ala Met Thr Val Asn Trp Ilie Ala 55 Gin Gin Leu Val Ser His Asp Leu Arg 70 Gin Asp Pro Arg Gly Phe Ala Gly Lys Leu Ser Ile Ala Ser Ser Asp Thr Gin 100 105 agt Ser cgt Arg t tg Leu 415 aac Asn gtg Val gag Giu Phe 10 Giu Met Arg Met Glu 90 Ara t cc Ser cag Gin 400 gtg Val at t Ile ttt Phe gca Ala Ile Al a Leu Tyr ILeu Arg lal aag Lys 385 cgc Arg ct t Leu gct Al a a gt Ser gct Ala 465 ggC Gly ctg Leu ccc Pro 420 gtg Val ccc Pro cgg Arg 1267 1315 1363 1411 1459 1507 1539 Cys Asn Ile Gly Ala Val M1et Leu lal Thr rhr Ala ;ly Asp Gly Th r Leu ValI Asp Gly Ile 110 Leu Se r Phe Arg Arg Gly Val WO 01/00804 WO 0100804PCT/IBOO/00922 Met Val1 Gly 145 Gin Thr Ala Tyr Val 225 Al a Thr Gly Arg Asp 305 Thr Leu Asp Lys Lys 385 Phe Tyr Le U Ser Asp 180 Thr Thr Ala Leu Gly 260 Val Gly Lys Arg Thr 340 ValI Gi u GI y Pro Val Ser Ile Leu Val 150 Gly Ala 165 Val Val Val Arg Val His Ala Gly 230 Ala Leu 245 Leu Thr Ala Ser Val Leu Ala Glu 310 Gly Thr 325 Arg Val Arg Asp Val Ala Glu Gly 390 Ala Asn 135 Val Arg Gln Arg Ala 215 Ala Gln Gin Arg Gl y 295 Glu Asp Ile Asn Ser 375 Gly Leu Trp Al a Gin Leu 185 Tyr Ala Phe Gin Leu 265 Ala Asp Ile Gin Al a 345 His Asp Len Tyr Val Lys Ala Gi y 190 Gly Leu Gly Asp Thr 270 Ser Ser Lys Leu Asp 350 Val1 Gly Gin Arg Vai Ala Leu Ala Arg Ala Ile Ala Phe Asp Pro Gin Val Leu Val 415 WO 01/00804 Leu Gin Asp Pro Thr Thr Ala Val Asp Ser Val Thr Glu Gin Asn Ile 420 425 430 Ala Gin Gln Val Ala Ala His Arg Ala Gly Lys Val Thr Ile Val Phe 435 440 445 Ser Glu Ala Pro Ala Trp Ser Ala Val Ala Asp Gin His Val Glu Ala 450 455 460 Ala Ala Leu Arg Glu Val Met Lys 465 470 <210> 283 <211> 1470 <212> DNA <213> Corynebacteriun glutamicum <220> <221> CDS <222> (1447) <223> RXN01190 <400> 283 cagggttttg atgagaacaa cacacaccgc ttcaagcatt ctgcgaagaa tgatcaggc PCT1BOO/00922 -g gcagcggggc aaggttgcgt ttggcgcatt ctttttgggg gaa Glu ctc Leu gtg Val1 ttg Leu gcc Ala gag Giu ttc Phe gtg Val1 gat Asp gtg Val1 gcc Ala gcg Al a tcg Se r atc Ile at t Ile cgc Arg ttg Leu aac Asn a ag Lys 75 t cc S er acc Thr ggt Gly gt g Val1 30 tct Ser tcc Se r gat Asp gat Asp t cg Ser atc Ile ggg Gly cgt Arg gcg Ala cgc Arg 80 ga t Asp gcg Al a atg tgg cag ctg tcg 115 Met Trp Gln Leu Ser 1 gtt gat cat gcg gtt 163 Val Asp His Ala Val ctt gtc gct ttt gtt 211 Leu Val Ala Phe Val ttc ggt tcg cgc gcg 259 Phe Gly Ser Arg Ala ctc cgc gta gag gta 307 Leu Arg Val Giu Val aat ttg gtg cct ggc 355 Asn Leu Val Pro Gly tct tcg acg cgt att 403 Ser Ser Thr Arg Ile 100 aca aaa ttt ctt oat 451* WO 01/00804 WO 0100804PCT/IBOO/00922 gca Ala ct t Leu ggc Gly 150 ggt Gly atc Ile gca Al a got Al a ttg Leu 230 ttg Leu ttg Leu gag Glu gaa Glu oca Pro 310 gcg Ala gtq Val 135 att Ile gcg Ala ggt Gly tca Ser ggt Gly 215 ctt Leu atc Ile ctg Leu Cgg Arg agc Se r 295 gcc Alia acc Thr 120 ctg Leu tot.
Ser ca g Gin ggc GI y gog Al a 200 att Ile got Ala gca Ala agc Ser gtg Val1 280 agc Ser ago S er tac Tyr Igta Val aaa Lys gca Al a gag Gi u 185 aga Arg ggt Gly ggt Gl y att Ile aac Asn 265 got Ala gaa Glu acg c Thr I otg Leu cog Pro agg Arg agt Ser 170 cgt Arg gog Ala gag Glu tgg Trp gtg ValI 250 tog Ser aat PAsn aca ['hr ~tt.
.e u ttc Let atc Ile agi Ser 155 gac Asp t gg T rp gog Ala ttg Leu Cgg Arg 235 ggt Gly a tt Ilie ttC Phe atc Ile oca Pro 315 ato I le *att Sle 140 gto Val ato Ile goo Ala gt t ValI too Ser 220 gtc Val gt g Val aat Asn tta Leu aat Asn 300 cao His agt 125 tog Se r aco Thr atg Met gtg Val gat Asp 205 att Ile aco Thr gog Al a gcc Ala aac PAsn 2B5 gao %sp 3gC 31Y gao Asp gga Gly cag Gin atg Met aag Lys 190 act Thr gog Al a acg Thr gtg Val tca Ser 270 ctc Leu 9gc Gly gao Asp Trp gtg Val1 cag Gin ggg GI y 175 act Thr gca Ala gtg Val ggg Gly tat Tyr 255 got Al a gao Asp gaa Glu aat 3,sn otg Leu gtt Val1 Igag *Glu 160 otg *Leu ttt Phe gt t Val1 aat Asn gag Glu 240 ttg Leu att Ile gaa Glu tto Phe ato Ile 320 gt 0 Val1 gca Ala 145 aag Lys ogo Arg ga Glu got Al a ttg Leu 225 ttg Leu toa Ser Ala tot Ser oto Leu 305 ttg Leu ggg Gi y 130 ctg Leu t tg Leu gtg Val aag Lys tog Ser 210 got Al a ggg Gly gag Glu cac His cag Gin 290 gt 0 Val1 got Ala t tg Leu got Ala gcg Ala ato Ile gog Ala 195 ggo Gly gog Al a ct Pro cog Pro ggt Gly 275 gca Ala ato Ile aca Thr t tg Leu ago Ser gag Glu sag Lys 180 tog Ser aaa Lys gtg Val1 Gly ati Ile 260 gca Ala cag Gin gtg Val1 cot Pro gtg Val1 aag Lys tot Se r 165 gog Ala cag Gin gto ValI ttg Leu cag Gin 245 ogo Arg gog Al a tao Tyr ccc Pro cat His 325 499 547 595 643 691 739 787 835 883 931 979 1027 1075 1123 got goc gao: att tto gaa ggt Ala Ala Asp Ile Phe Glu Gly 330 aco ttg cgg tca sat att too atg aat Thr Leu Arg 335 Ser Asn Ile Set Met Asn 340 WO 01/00804 cat gag gac aaC gtg Cca att gat ccg His Giu Asp Asn Val Pro Ile Asp Pro 345 350 ctg act gac atc att gag gtg gac gga Leu Thr Asp Ile Ile Glu Val Asp Gly 360 365 acg gga agc aat tta tcg ggt ggg cag Thr Gly Ser Asn Leu Ser Gly Gly Gin 375 380 agg gcg ttg cat gca gac gcg gaa gta Arg Ala Len His Aia Asp Ala Gin Val 390 395 agc gcg gtg gat tca gtg acg gag gtg Ser Ala Val Asp Ser Val. Thr Gin Vai 410 cag ctg cga gca ggc aaa acc acc att Gin Leu Arg Ala Gly Lys Thr Thr Ile 425 430 ttt tac aac ttg gcg gat cgg gtg att Phe Tyr Asn Leu Ala Asp Arg Val Ile 440 445 gcatcatcga cac <210> 284 <211> 449 <212> PRT <213> Corynebacteriun giutamicun <400> 284 Met Trp Gin Len Ser Giu Ala Leu Val 1 5 Vai Asp His Ala Val Len Thr Lys Asp 25 Len Val Ala Phe Val Val Len Phe Vai 40 Phe Gly Ser Arg Ala Len Asn Arg Ala 55 Len Arg Val Giu Val Ala Asp His Ala 70 Asn Len Val Pro Gly Gin Val Met Ser Ser Ser Thr Arg Ile Phe Gly Gin Ile cag Gin ctt Leu cgt Arg ctg Leu tct Ser 415 gt g Val1 t ca Se r att Ile gcg Al a cga Arg 385 ctg Len gcg Ala a gt Ser gt c Val1 Cgc gct tct Arg Ala Ser 355 ccg gtg cgc Pro Val Arg 370 gtg gct ttg Val Ala Len atg gat cca Met Asp Pro cag ggg att Gin Gly Ile 420 tct tcg ccc Ser Ser Pro 435 taatttgatq PCT/IBOO/00922 1171 1219 1267 1315 1363 1411 1457 1470 Pro 10 Len Val1 Val1 Leu krg 90 Aila Arg Ser Phe Asn Th r Gly Ile Leu Phe Gin Len Al a Val1 Gly Val Ser Ser Asp Asp Se r Len Ile Val Gly Asn Arg His Ala Pro Axg Ala Asp Ala Ala WO 01/00804 PCT/IBOO/00922 Thr Va1 Ala 145 Lys Arg Glu Ala Leu 225 Leu Ser Ala Ser Leu 305 Leu Asn Gly Gly 130 Leu Leu Val Lys Ser 210 Ala Gly Glu His Gin 290 Val Ala Ile Phe 115 Leu Ala Ala Ile Ala 195 Gly Ala Pro Pro Gly 275 Ala Ile Thr Ser Leu Gly Ala Leu Val Leu Ser Lys Gly 150 Glu Ser Gly 165 Lys Ala Ile 180 Ser Gin Ala Lys Val Ala Val Leu Leu 230 Gly Gin Leu 245 Ile Arg Leu 260 Ala Ala Glu Gin Tyr Glu Val Pro Pro 310 Pro His Ala 325 Met Asn His 340 Ala Thr Tyr Leu Leu Ile Ser Asp Trp Leu 120 125 Va 13! Il( Ala Gl Sex Gly 215 Leu Ile Leu Arg Ser 295 Ala Ala Glu rhr Gly 375 l a 1 Leu Ser Gin Gly Ala 200 Ile Ala Ala Ser Val 280 Ser Ser Asp Asp Asp 360 Ser Leu I Va Ly Ala Glu 185 Arg Gly Gly Ile Asn 265 Ala Glu Thr Ile Asn 345 Ile Asn His I Pro Arg Ser 170 Arg Ala Glu Trp Val 250 Ser Asn Thr Leu Phe 330 Va1 Ile Leu Ala Il Sei 155 Asp Trp Ala Leu Arg 235 Gly Ile Phe Ile Pro 315 Glu Pro lu Ser ksp 395 Ile 140 Val Ile Ala Val Ser 220 Vai Vai Asn Leu Asn 300 His Gly Ile Val Gly 380 Ala Ser Thr Met Val Asp 205 Ile Thr Ala Ala Asn 285 Asp Gly Thr Asp Asp 365 ly Glu Gly Gin Met Lys 190 Thr Ala Thr Va1 Ser 270 Leu Gly Asp Leu Pro 350 Gly Gin Val Va1 Gin Gly 175 Thr Ala Va1 Gly Tyr 255 Ala Asp Glu Asn Arg 335 Gin Leu Arg Leu Val Glu 160 Leu Phe Va1 Asn Glu 240 Leu Ile Glu Phe Ile 320 Ser Va1 Asp Gin Val Ile Arg Aia Ser Gly Leu 355 Ala Pro Val Arg Asp Thr 370 Arg Val Ala Leu Ala Arg 385 390
I
Leu Met Asp Pro Thr Ser Ala Val Asp Ser Val Thr Giu Val Ser Ile WO 01/00804 PCT/IBOO/00922 405 410 415 Ala Gin Gly Ilie Lys Gin Leu Arg Ala Gly Lys Thr Thr Ile Val Val 420 425 430 Ser Ser Ser Pro Ala Phe Tyr Asn Leu Ala Asp Arg Val Ile Ser His 435 440 445 Val1 <210> 285 <211> 1368 <212> DNA <213> Corynebacteriui glutamicum <220> <221> CDS <222> (101)..(1345) <223> RXN01102 <400> 285 attctatggt tgttgggaga gatgacttaa tttggaatca cattgagcaa cttcccagca tgtggaaaag CCCaggtttc cgggctttaa cacgcgctga gcg gtt Ala Val ccg cta Pro Leu aec act Thr Thr CCC gct Pro Ala qca ttc Ala Phe cca att Pro Ilie gcq ctc Ala Leu gca gcg ttc Ala Ala Phe gtc ctc aac Val Leu Asn atc ttc atg Ile Phe Met Ctg cgg aaa Leu Arg Lys ctg ggt gtg Leu Gly Val 75 gtg ctg gta Val Leu Val gtC gca gaa Val Ala Glu 105 ggc agt Gly Ser aac ggc Asn Gly qca qct Ala Ala att ggc Ile Gly 60 cca gcc Pro Ala gtg tcC Val Ser tct gcg Ser Ala tqg Trp 9ga Gly 30 aca Thr tac Tyr atc Ile gca Ala t ig Leu 110 tca Ser 15 t ca Ser gt g Val1 ac C Thr ggg Gly ctt Leu 95 gtg Val1 ctc Leu agc Se r atc Ile C Ca Pro tac Tyr 80 cga Arg gct Al a gt g Val1 1 ct t Leu gct Ala act Thr gtg Val1 atc Ile gga Gly gaa Glu gct gtCcCtC Ala Val Leu
CCC
Pro gcc Ala att Ile gct Ala agc Ser g gg Gly gtt Val1 115 gtC Val1 gqt Gly ttC Phe ttc Phe gtC Val1 ttc: Phe 100 ccc Pro qtg Val1 gt a Val1 gcC Ala act Thr gcc Al a gag Glu ggt Gly gta Val1 115 163 211 259 307 355 403 451 WO 01/00804 WO 0100804PCT/IBOO/00922 cgc ttC ttg Arg tcC Ser ggc Gly 150 9gg Ala caa Gin gtg Val1 gea Al a tta Leu 230 t ca Ser gtg Val gtc Val ttg Leu aac: Asn 310 tCe Ser Phe caa Gin 135 tac Tyr gtg Val ca Pro ct g Leu gt g Val1 215 ggt Gly atg Met cct Pro gt t Val1 att Ile 295 gaa Glu gaa Giu *Leu 120 atg Met aac *Asn atg Met cag Gin gt t Vali 200 tct Ser get Al a gig Val ggt Gi y tta Leu 280 ata Ile gcg Ala gcc Ala gg Gl~ ct t Let.
gtc Val.
tgt Cys gt g Val1 185
CCC
Pro tea Ser gca Al a ttC Phe ace Thr 265 atc Ile ggt Gly ttg Le u tcC 3e r -aaa gct tet ~Lys Ala Ser -tt cetg ect Phe Leu Pro 140 gtc tat gtt -Val Tyr Val 155 *ctg cgt att Leu Arg Ile 170 agc gaa cag Ser Glu Gin tee ttg get *Ser Leu Ala ttc ctt cca Phe Leu Pro 220 tta gcg ggt Leu Ala Gly 235 cgc tac ctg Arq Tyr Leu 250 acg atg att Thr Met Ile ace: gtc: aca Thr Vai Thr gca gtg atg Ala Val Met 300 ctt tea atg Leu Ser Met 315 gee ate: tgg Ala Ile Trp, gga Giy 125 gcc Ala tta Leu ceg Pro gag Giu gtt ValI 205 get Al a at t Ile tcc Ser cct Pro ate Ile 285 ttt Phe tt I Phe aat a ksn I atc Met Gl ggt Gly eag Gin egt Arg 190 acc Thr gea Al a att Ile Gly get Alia 270 te Phe ggt Gly :te Phe tc ttg Leu ttg Leu gee Ala Igt Val 175 tct Ser agt Se r gte Val1 tta Leu gtt Val 255 cag Gin eaa Gin ggt Giy Arg gee Ala gge Gi y geg Ala gtt Val1 160 a ag Lys gitt ValI ttg Leu att Ile tee Ser 240 ate Ile atc Ile Gi y Alia ctt LeuI 320 ~tttc Phe gta Val tta Leu 145 at c gea Ala tee Ser tea Ser gag Giu 225 at t Ile get Ala att Ile t gg rrp ttt Phe 305 :et Pro ;at ~sp ttt *Phe 1 ggt G15 gea *Ala gccj Ala acc Thr atg Met 210 tta Leu ac Thr gae Asp ggg Giy tee Ser 290 gge Gi y ege Arg t eg Ser att Sle gae: Asp eta Leu gca Ala tgg Trp 195 act Thr ga t Asp ggt Gly ege Arg t te Phe 275 gt g ValI atg Met act Thr gga Gly gge Gly eaa Gin gt t Val1 aag Lys 180 aag Lys ttt Phe eea Pro ggt Gly ege Arg 260 tta Leu tgg Trp gt g ValI aga Arg aea Thr ctt Leu ttt Phe gca Al a 165 cag Gin ttg Leu gge Gly gga Gly t Ct Ser 245 ggt Gly ggt Gl y ett Leu ea a Gin gte Val1 325 gga Gly 499 547 595 643 691 739 787 835 883 931 979 1027 1075 1123 1171 330 335 340 ate: gga age: ttc etc ett ggc ata gtt gee gca teg ctt get tac agt WO 01/00804 Ile Gly Ser Phe Leu Leu Giy Ile Val 345 350 ggt gct ttt ggt tcc gga gce gtg gtg Gly Ala Phe Gly Ser Gly Ala Val Val 360 365 acc ace gcc gat cga ate att ggg cgg Thr Thr Ala Asp Arg Ile Ile Giy Arg 375 380 aac acc cgc gcg cgt ttg cgc cag gtg Asn Thr Arg Ala Arg Leu Arg Gin Val 390 395 caa ggg ctg cgc aac agg cgc aaa gat Gin Gly Leu Arg Asn Arg Arq Lys Asp 410 ccc <210> 286 <211> 415 <212> PRT <213> Corynebacterium glutamicum -400> 286 Vai Ala Vai Leu Val Ala Val Ala Ala 1 5 Leu Leu Pro Val Val Pro Leu Ala Val 25 Ala Val Aia Gly Ala Thr Thr Gly Ile 40 Thr Gin Ile Phe Thr Pro Ala Ala Leu 55 Vai Met Ala Phe Ala Ala Phe Met Leu 70 Ile Phe Ser Val Glu Pro Ile Pro Val Gly Ile Gly Phe Gly Ala Leu Thr Val 100 105 Glu Leu Val Pro Val Arg Phe Leu Gly 115 120 Val Phe Ile Gly Leu Ser Gin Met Leu I 130 135 Leu Gly Asp Gin Phe Gly Tyr Asn Val N 145 150 PCT/IBOO/00922 Ala att Ile eac His cca Pro cge Arg 415 Ala 10 Leu Phe Arg Gly 1 Leu 90 Ala Lys I Phe I lal T 1 Ala Ser Leu Ala Tyr Ser 355 ttg ttt gqa ate gtt ttg Leu Phe Giy Ile Val Leu 370 cge att act gaa tac aac Arg Ile Thr Glu Tyr Asn 385 gtc gct egg cgt gca gtg Val Ala Arg Arg Ala Vai 400 405 taaaacgctt ttcgacgcca 1219 1267 1315 1365 1368 Phe Asn Met Lys Va1 75 Val ;lu la ,eu yr .55 Gly Ser Trp Asn Gly Gly Ala Ala Thr Ile Gly Tyr Pro Ala Ile Val Ser Ala Ser Ala Leu 110 Ser Gly Met 125 Pro Ala Gly 140 Val Leu Gly Ser Ser Val Thr Gly Leu Val Leu Leu Ala Leu Ser Ile Pro Tyr Arg Ala Gly Ala Va1 160 WO 01/00804 PCT/IBOO/00922 Ile Ala Leu Val Ala Ala Val Met Cys Leu Arg Ile Pro Gin Val Lys 165 170 175 Ala Ala Ala Lys Gin Gin Pro Gin Val Ser Giu Gin Giu Arq Ser Val 180 185 190 Ser Thr Trp Lys Leu Val Leu Vai Pro Ser Leu Ala Vai Thr Ser Leu 195 200 205 Ser Met Thr Phe Gly Ala Val Ser Ser Phe Leu Pro Ala Ala Vai Ile 210 215 220 Giu Leu Asp Pro Giy Leu Gly Ala Ala Leu Ala Gly Ile Ilie Leu Ser 225 230 235 240 Ile Thr Gly Gly Ser Ser Met Val Phe Arg Tyr Leu Ser Gly Val Ile 245 250 255 Ala Asp Arg Arq Gly Val Pro Gly Thr Thr Met Ile Pro Ala Gin Ile 260 265 270 Ilie Gly Phe Leu Gly Val Val Leu Ilie Thr Val Thr Ilie Phe Gin Gly 275 280 285 Trp Ser Val Trp Leu Leu Ile Ile Gly Ala Val Met Phe Gly Gly Ala 290 295 300 Phe Gly Met Val Gin Asn Glu Ala Leu Leu Ser Met Phe Phe Arg Leu 305 310 315 320 Pro Arg Thr Arg Val Ser Glu Ala Ser Ala Ile Trp Asn Ile Ala Phe 325 330 335 Asp Ser Gly Thr Gly Ile Giy Ser Phe Leu Leu Gly Ile Val Ala Ala 340 345 350 Ser Leu Ala Tyr Ser Gly Ala Phe Gly Ser Gly Ala Val Val Ile Leu 355 360 365 Phe Gly Ilie Val Leu Thr Thr Ala Asp Arg Ile Ilie Gly Arg His Arg 370 375 380 Ilie Thr Giu Tyr Asn Asn Thr Arq Ala Arg Leu Arg Gin Val Pro. Val 385 390 395 400 Ala Ar g Arg Ala Vai Gin Gly Leu Arg Asn Arg Arg Lys Asp Arg 405 410 415 <210> 287 <211> 348 <212> DNA <213> Corynebacteriun glutamicum <220> <221> CDS WO 01/00804 <222> (325) (223> RXN00788 <400> 287 PCT/IBOO/00922 cgcatccctc tagttttcca tc ttgatccagc actgcttgca gt 9ga Gly acc Thr ttg Leu cg t Arg cag Gin aac Asn act Thr tcc Ser gcg Al a caa Gin .acctcaat gaacggcgct aactccggtt cattqcgcaa .gaqgcctc attagttggc atg gcc tcc tcc atc Met Ala Ser Ser Ile 1 ctt gga aat gct gtt gct gcc tgg ctt gct Leu Gly Asn Ala Val Ala Ala Trp Leu Ala tcc ctt gga ctc aca. tca gcc gga tta gtt Ser Leu Gly Leu Thr Ser Ala Gly Leu Vai ctc gga cta gtg ttg gcc atc gtg gct gtg Leu Gly Leu Val Leu Ala Ile Vai Ala Val 45 caa ggc acc caa gcg acc atc agc gtt gtg Gin Gly Thr Gin Ala Thr Ilie Ser Val Val taaataattt ctctcttcta att <210> 288 (211> '212> PRT <213> Corynebacterium giutamicum <400> 288 Met Ala Ser Ser Ilie Asn Ile Giy Vai Phe Asn Leu Gly Asn Ala Val 1 5 10 Ala Ala Trp Leu Ala Giy Aia Thr Ile Thr Thr Ser Leu Gly Leu Thr 25 Ser Ala Gly Leu Vai Gly Gly Leu Met Thr Ser Leu Gly Leu Val Leu 40 Ala Ilie Val Ala Vai Val Leu Arg Arg Lys Aia Gin Gly Thr Gin Ala 55 Thr Ilie Ser Val Val Glu His Gin Pro Ala Gin 70 ':210> 289 <211> 1764 <212> DNA <213> Corynebacterium giutamicum wo 01/00804 WO 0100804PCT/IBOO/00922 <220> <221> CDS <222> (1741) <223> RXN0219 <400> 289 ttcggtccgc tctggcaaaa atggctggct gecacctcgg gcttaaattg cttgtcgacg cctagtgcca caatggagac cgcagcagct taagggctgg atg ace gaa aca ctt Met Thr Glu Thr Leu gtg Val1 ga t Asp gt c Val1 gaa.
Glu gtg Val1 gca Ala atg Met ttg Leu gca Al a ttt Phe 150 gt g Val1 gt g Val1 aat Asn aag Lys gge Gly gt t Val1 gat Asp gcc Al a gee Al a 135 gag Glu aat Asn a at Asn ggc Gly eca Pro tac Tyr tac Tyr gac Asp gat Asp 120 gat Asp Ctt Leu ggC Gly ctc Leu gct Ala ctg Leu ttg Leu att Ile ac Thr 105 gca Al a ttg Leu
CCC
Pro ct t Leu ac Thr ggt Gly get Ala cca Pro gct Ala gee Ala t ac Tyr ga t Asp ace Th r g ca Ala gta Val aaa Lys gga Gi y ca g Gin 75 cgt Arg gaa Glu gc Al a gaa.
Glu tcg Ser 155 ggc GI y gct Al a tee Ser act Thr 60 gaa Glu cga Arg gcg Ala gag Giu cgc Arg 140 acg Thr ggC Gly gee Ala aca Thr 45 ate Ile cac His ac Thr ttt Phe gcg Ala 125 ate Ile ctg Leu tat Tyr ggC Gly 30 ttt Phe geg Ala a cc Thr ggC Gly ggt GI y 110 ct g Leu
CCC
Pro atg Me t ggg Glyj 15 gat Asp eta Leu ctt Leu ege Arg t gc Cys 95 gcg Al a gat Asp ate Ile gaa Glu cac His gte Val aaa Lys t eg Se r aeg Thr 80 ca a Gin gat Asp egg Arg gtg Val gga GI y 160 ege Arg gt g Val1 att Ile eca Pro tet Ser gct Ala e ca Pro t gg T rp etc Leu 145 Ct t Leu a ca.
Thr ggc GI y et g Leu gee Ala gga Gi y gca Ala gac Asp atg Met 130 get Ala tea Se r tta.
Leu gt t Val1 geg Ala gat Asp gag Glu aca Thr aac Asn 115 gee Al a ga t Asp ggc Gly ttt aac Phe Asn gte ggc Val Gly ggc gtg Gly Val get ttt Ala Phe aeg ate Thr Ile act gee Thr Ala 100 get gee Ala Ala agt ggc Ser Gly ttg gge Leu Gly ggg eag Gly Gln 165 115 163 211 259 307 355 403 451 499 547 595 gca gee egg gte Ala Ala Arg Val ggg Gly 170 etg geg geg tta etg ttg Leu Ala Ala Leu Leu Leu 175 tea egt ttt Ser Arg Phe gae att Asp I~le 180 WO 01/00804 WO 0100804PCTIIBOO/00922 gtq ValI ca a Gin agc Se r ctc Leu 230 t cc Ser tat Tyr acg Thr gca Ala gaa Glu 310 tta Leo gte Val gca Ala gt a Val1 aaa Lys ctt etc gac Leo Leu Asp Ctg Leu cat His 215 ga t Asp tac Tyr gag Glu cag Gin cct Pro 295 aag Lys gaa Glu ggt Gb y agc Se r aat Asn 375 toe Ser gag Giu 200 ga t Asp ctg Leu ott Leu gaa Glu cgt Arq 280 gac Asp cag Gin ga a Gb u aag Lys ttc Phe 360 get Ala a ca Thr 185 aat Asn cgt Arg cac His gag Gin ttt Ph e 265 gaa Glu aao As n got Ala gt t Val1 gcg Ala 345 acc Thr ggC Gly ttg Leo gag Glu ttt Phe gag Glu caa Gin ga a Glu 250 gcg Ala tgg V rp gao Asp caa Gin gaa Gin 330 t cg Ser caa Gin ga t Asp :tg eu ccc ace aac Pro Thr Asn gat ttg gat etc gao Asp Leo Asp Leu Asp gtt Val ttt Phe aat Asn 235 ego Arg gaa Gin tot Se r aaa Lys aaa Lys 315 gag Glu ogg Arg 9gc Gly cgc Arg cgc Arg cag Gln Ott Leu 220 tc Ser gea Al a aag Lys ag t Se r ott Leu 300 gte Val1 cca Pro toa Se r ga t Asp att Ilie 380 gga 31y ggg Gly 205 *tcc ISer cac *His gtg ValI a ag Lys cac His 285 egg Arg ego Arg og t Arg agt Ser ttc Phe 365 ggC Gly ctaI Leo X :pu Ct t Len agg Arg cat His eta Leu aag Lys 270 gg t Gly aag.
Lys eag Gin aaa Lys tot Ser 350 ace Tb r atc Ile ttg Lieu cgc Arg t gt Cys gtt Val1 ego Arg 255 gao Aspn gte Val1 aaa Lys atg Met gaa Gin 335 gt t Val ttg Len aca Thr gga Gly ggg Gly qtg Vai tat Tyr 240 eag Gin ott Len ego Arg gee Al a gaa Gin 320 tgg Trp gt t ValI gga Gly gga Gly aac Asn 400 gga Gly ace Thr 225 ggC Gly cac His gtg Val1 aat Asn get Ala 305 ago Se r aaa Lys too Ser o ca Pro ~ce Pro 385 ca a Gln gtc Val1 210 act Thr ggt Gly gee Ala gca Ala get Ala 290 geg Ala ego Arg ctg Leu acg Thr gta Val 370 aac As n gaa Gin gitg Val gga Gly og t Arg egt Arg 275 att Ile ga a Gin ate Ile eag Gin t tg Len 355 toe Se r ggt Gb y ccc Pro ct g Leu tat Tyr gao Asp 260 got Ala aaa Lys toe Ser get Ala ttc Phe 340 aa t As n ate Ile get Ala ace Thr ggt ott gag Gly Leu Giu 195 gta ctg gte Val Leu Val gaa Giu gat Asp 245 caa Gin ega Arg cgt Arg a gt Ser egg Arg 325 age Se r ga t Asp caa Gin ggt Gly age Ser 405 691 739 787 835 883 931 979 1027 1075 1123 1171 1219 1267 1315 1363 390 395 ggt aet gee aeg atg ggc aeg age qtg geg ate gga gaa ate gat eag WO 01/00804 WO 0100804PCT/IBOO/00922 Gly Thr Ala Thr Met Gly Thr Ser Val Ala Ile Gly Giu Ile gca cga Ala Arg aag cat Lys His aaa ttt Lys Phe 455 tet cct Ser Pro 470 ggc gtc Gly Val gag gcc Glu Ala ttg ctg Leu Leu aat cgt Asn Arg 535 tta Leu 425 cca Pro ctg Leu gag Gin gtg Val gag Ci u 505 gt C Val1 tgg 410 ct t Leu gac Asp aa t Asn cgc Arg ctt Leu 490 caa Gin acg Thr cat gat cca Asp Pro tta ccq Leu Pro gat aat Asp Asn 460 acg cgc Thr Arg 475 gtt ctt Val Len ttg gag Leu Giu cac gat His Asp gtc gag cag ttg Gin Leu 430 atc agt Ile Ser 445 cat gig His Val gcc gga Ala Gly gat gag Asp Gin caa gcg Gin Ala 510 cgt cgc Arg Arg 525 gct ggc 415 c ca Pro gag Glu ga a Gin ct t Len ccc Pro 495 i ig Len atg Met gaa att Ile cgc Arg gac Asp 465 ctg Leu aac Asn tcg Se r ga c Asp agg tct gcg Ser Ala 435 aca ctg Thr Leu 450 gic gaa Val Gin cta cag Leu Gin cac ctt His Len tat gat Tyr Asp 515 gct gig Ala Val 530 gag cia Giu Leu Asp Gin 420 ttt gaa Phe Giu ctc gcg Len Ala aag cta Lys Leu gig cgg Val Arg 485 gac cig Asp Leu 500 ggt gig Gly Val cag acc Gin Thr 1411 1459 1507 1555 1603 1651 1699 1741 1764 Arg Trp His Vai Gin Ala Gly Gin Val Arg taaccgtttc cgtattgatg cca <210> 290 <211> 547 <212> PRT <213> Corynebacierium giutamicui <400> 290 Met Thr Giu Thr Leu Val Vai Asn Gly Leu Aia Gly Gly Tyr Gly His 1 5 10 Arg Thr Leu Phe Asn Asp Val Asn Len Thr Val Ala Ala Gly Asp Val 25 Val Gly Val Vai Gly Val Asn Gly Ala Gly Lys Ser Thr Phe Len Lys 40 Ile Leu Aia Gly Val Giu Lys Pro Len Ala Giy Thr Ile Ala Len Ser 55 Pro Ala Asp Ala Phe Vai Gly Tyr Leu Pro Gin Gln His Thr Arg Thr WO 01/00804 WO 0100804PCTIIBOO/00922 Ser A].a Pro Trp Leu 145 Leu Se r Leu Gly Thr 225 Gi y His Val.
Asn Ala 305 Ser Lys Ser Gly Ala Asp Met 130 Ala Se r Ar g Asp Val 210 Thr cay Ala Ala Ala 290 Ala Arg Leu Th r Glu Thr Asn 115 Ala Asp Gly Phe Gly 195 Val Val.
cay Arg Arg 275 I le Glu Ile Gin Leu Th r Tb r 100 Ala Se r Leu Gly Asp 180 Leu Leu Leu Tyr Asp 260 Ala Lys Ser Ala Phe 340 Asn Ile Al a Ala Gi y Gly Gin 165 Ile Glu Val.
Glu Asp 245 Gin Arg Arg Ser Arg 325 Se r A~sp Ala Val.
Met Asp Leu Ala Ala Ala 135 Phe Glu 150 Ala Ala Val Leu Gin Leu Ser His 215 Leu Asp 230 Ser Tyr Tyr Glu Thr Gln Ala Pro 295 Giu Lys 310 Leu Glu Val Gly Ala Ser Tyr Ile Asp Thr 105 Asp Ala 120 Asp Leo Leu Pro Arg Val Leu Asp 185 Glu Asn 200 Asp Arg Leu His Leu Glu Giu Phe 265 Arg Giu 280 Asp Asn Gin Ala Glu Val.
Lys Ala 345 Phe Thr Ala 90 Ala T yr Asp Thr Gly 170 Giu Phe Giu Gin Glu 250 Ala Trp Asp Gin Glu 330 Se r Gin Arg Arg Glu Ala Ala Giu Glu Ar g 140 Ser Thr 155 Leu Ala Pro Thr Val Gin Phe Leo 220 Asn Ser 235 Arg Ala Glu Lys Ser Ser Lys Leu 300 Lys Val.
315 Glu Pro Arg Ser Gly Asp Cys Ala Asp Ile Glu Leu 175 Leu Arg Cys Val.
Arg 255 Asp Val1 Lys Met Glu 335 Va].
Leu 355 360 365 Pro Val Ser Ile Gin Val. Asn Ala Gly Asp Arg Ile Gly Ile Thr Gly WO 01/00804 PCTfIBOO/00922 370 375 380 Pro Asn Gly Ala Gly Lys Ser Thr Leu Leu Arg Gly Leu Leu Gly Asn 385 390 395 400 Gln Glu Pro Thr Ser Gly Thr Ala Thr Met Gly Thr Ser Val Ala Ile 405 410 415 Gly Giu Ilie Asp Gin Ala Arg Ala Leu Leu Asp Pro Gin Leu Pro Leu 420 425 430 Ile Ser Ala Phe Glu Lys His Val Pro Asp Leu Pro Ilie Ser Glu Val 435 440 445 Arg Thr Leu Leu Ala Lys Phe Gly Leu Asn Asp Asn His Val Glu Arg 450 455 460 Asp Val Giu Lys Leu Ser Pro Gly Glu Arg Thr Arg Ala Gly Leu Ala 465 470 475 480 Leu Leu Gin Val Arg Gly Val Asn Val Leu Val Leu Asp Glu Pro Thr 485 490 495 Asn His Leu Asp Leu Glu Ala Ile Glu Gin Leu Giu Gin Ala Leu Ala 500 505 510 Ser Tyr Asp Giy Val Leu Leu Leu Val Thr His Asp Arg Arg Met Leu 515 520 525 Asp Ala Val Gin Thr Asn Arg Arg Trp His Val Glu Ala Gly Giu Val 530 535 540 Arg Glu Leu 545 <210> 291 <211> 1638 <212> DNA <213> Corynebacteriun giutamicum <220> <221> CDS <222> (101)..(1615) <223> RXN01605 <400> 291 attqaagtca qcgccgagga agccqcgagg gaatcagacg acgggcacct actacttcgg cattqaaatt ccgaagaact tcagcgattc tattgccagc gtg acc agc gat tca 115 Val Thr Ser Asp Ser 1 ccc gcg cca gca acc gtc aac gcg gta ttc aac aac agc aac ggc ttc 163 Pro Ala Pro Ala Thr Val Asn Ala Val Phe Asn Asn Ser Asn Gly Phe 15 WO 01/00804 WO 0100804PCT/IBOO/00922 att gcc Ile Ala tcc atg Ser Met atg Met ttC Phe acg Thr gcc Ala ggt Gly 9gC Gly ctg Leu ga t Asp 150 gtt Val acc Thr gtg Val1 acc ga C Asp t cc Ser cte Leu gac Asp gcg Al a tc Ser tet Ser 135 ggc Gly cca Pro att Ile gac Asp ctg acg Thr a cc Thr agc Ser ggc GI y ca a Gin gcg Ala 120 gcg Ala gtg Val1 gac A~sp gee Alia tcc Ser 200 ~aaa gaa Giu ttg Leu gat Asp gcg Al a tcg Ser 105 gct Al a gge Gly gge Gi y at c Ile tct Ser 185 gct Alia gc ctg ggc: Leu Gl ttc ggc Phe Gly ggc gac Gly Asp ggc gtc Gly Val 75 gte acc Val Thr ctt gcc Leiu Aia aca -ggc Thr Gly acc gcc Thr Ala caa ctt Gin Leu 155 aac tet Asn Ser 170 gaa cta Glu Leu gtg agc Val Ser gga tcc Gly Ser aac cag gtg gtc Asn Gin Val Val 30 *gte cgc Val Arc ggc atc Gly Met 60 ggt tc Gly Ser ctg cge Leu Arg gac ggc Asp Gly agc caa Ser Gin 125 caa cta Gin Leu 140 gtc gac Val Asp cag ttg Gin Leu tct gat Ser Asp gca tee Ala Ser 205 agc caa Ser Gin 220 ttg gcc Leu Ala att gtc Ile Va] aac caa Asn Gir *gcc aac *Ala Asn gac ggc Asp Gly 95 gcc agc Ala Ser 110 acg etc Thr Leu gge eaa Gly Gin caa gta Gin Val atc acc Ile Thr 175 ccc tcc Pro Ser 190 cag caa Gln Gin etc agc Leu Scr gca ggt Ala Gly aac act gtt gtg gag acc Asn Thr Val Val Giu Thr Igat aac .Asp Asn igcc C iAla Ala gac ggt i Asp Gly 80 ate gca Ile Ala cag etc Gin Leu gcc gac Ala Asp ggc gca Gly Ala 145 gca cca Ala Pro 160 ctg cgc Leu Arg agc ace Ser Thr eta gca Leu Ala ate gqt Ile Gly 225 tee gaa Ser Glu atg Met gaa Glu gea Ala a gt S er gac Asp ggt Gly 130 ace Th r cig Leu gac Asp tac Tyr gee Al a 210 gca Ala cag Gin etc Leu ggt Gi y gtt Val1 gcc Ala ace Thr 115 eta Leu eag Gin ace Thr ggC Gly ege Arg 195 gge Gi y ege PAxg cta Leu gte Val gee Ala cag Gin aa t Asn 100 ggc Gly tee Ser gt t ValI gee Ala gca Ala 180 tee Ser et g Leu ace Thr gtt Val1 ggt Gly act Th r ctt Le u gag Giu etc Leu age Ser tea Ser tat Tyr 165 gee Ala ggc GI y eaa Gin etc Leu gtt Val1 211 259 307 355 403 451 499 547 595 643 691 739 787 835 Thr Leu Lys 215 get gat ggc ace age eaa Ala Asp Gly Thr Ser Gin 230 235 240 245 ggc gca caa gea ctg cgc gac gge ace gte cag ctt gat gaa ggc tee WO 01/00804 Gly Ala Gin Ala Leu Arg Asp Gly Thr Val Gin Leu Asp Giu 250 255 PCTIIBOO/00922 Gly Ser 260 agc Sex ttc Phe caa Gin ttC Phe 310 ct g Leu cga Arg caa Gin c ca Pro gta Val 390 gca Al a tcC Se r ttc Phe atg Met gaa Giu gct Ala gca Al a 295 atg Met cac His ggc Gly gca Ala gct Al a 375 ttc Phe 99C Gly ggt Gi y ca c His atc Ile 455 ct C Leu gac Asp 280 gqa Gl y gct Ala cca Pro acc Thr acc Thr 360 cac His atc Ile cg t Arg ggc Gly acc Thr 440 ttc Phe gcc Ala 265 ggC Gly gac Asp qtc Val1 atc Ile ctg Leu 345 atc Ilie cca Pro tcc Se r gtg Val1 cta Leu 425 t ac Tyr aac Asn ct c Leu gca Al a acc Thr ggc Gly agt Ser 330 gca Ala atg Met gct Ala att Ile ctg Leu 410 tac Tyr ga c Asp gaa Gi u aaa Lys *gac Asp aca Thr ctg Leu 315 cgc Arg agc Se r tgg Trp gga Gly a cc Thr 395 tcc Ser cca Pro ccg Pro a cc Thr ctc Leu acc Thr ccg Pro 300 ttc Phe cgc Arg tac Tyr g ca Ala ctg Leu 380 cat His atc Ile cca Pro atc Ile cca Pro 460 acc Th r acc Thr 285 ctc Leu atg Met gca Al a ct t Leu gt a ValI 365 tgg Trp atg Met gtg Val1 gaa Glu acc rhr 445 L cc Ser gac Asp 270 atc Ile ttc Phe gga Gi y ct c Leu cca Pro 350 ctg Leu atg Met ttc Phe atg Met acc Th r 430 tac Tyr aac Asn ggc Gly gca Al a ggt Gly gca Al a ga c Asp 335 tca Se r tac Tyr gc9 Al a aac As n atg Met 415 cag Gin gca Al a gac Asp gca Al a a cc Thr att Ile acc Thr 320 tcc Ser aca Thr ttc Phe atg Met aac Asn 400 t cc Ser cca Pro g tc Val1 cca Pro agc Se r cca Pro ggt Gly 305 gtt Val cgc Arg qtc Val ct g Leu gt c Val1 385 gt g ValI ttc Phe gca Ala aac As n cgc Arg 465 caa Gin gtt Val 290 ctc Leu gcc Al a at g Met tta Leu ct c Leu 370 gcc Al a gca Ala cag Gin t tc Phe ctc Leu 450 ttc Phe gta cca Val Pro 275 gaa aca Giu Thr gca cca Ala Pro tgg atg Trp Met gga ggc Gly Gly 340 qc ctt Gly Leu 355 gac ctc Asp Leu atc tca Ile Ser gga ccc Gly Pro cta gtc Leu Val 420 ttc cac Phe His 435 gtg cgc Val Arg ata caa Ile Gin a cc Thr gaa Giu ttc Phe atc Ile 325 ttc Phe ggc Gly aat Asn tgg Trp tcc Se r 405 tcc Ser tgg Trp caa Gin gca Ala 931 979 1027 1075 1123 1171 1219 1267 1315 1363 1411 1459 1507 1555 atc tgg gta Ile Trp Val ctg ctc ttc atc tgg gca ctg atg ctc gcc atc tcc acc Leu Leu Phe Ilie Trp Ala Leu Met Leu Ala Ile Ser Thr wo 01/00804 WO 0100804PCTIIBOO/00922 470 ctg gcg aat Leu Ala Asn gaa. ctg aag Giu Leu Lys 475 480 485 aga aca aac aag gtt ctt cgc atg aag gac tac cac cca Arg Thr Asn Lys Val Leu Arg Met Lys Asp Tyr His Pro 490 495 500 gtc taaaagcttt tcccgcccgg ttc Val1 505 1603 1638 <210> 292 <211> 505 <212> PRT <213> Corynebacterium glutamicum <400> 292 Val Thr Ser Asp Sex Pro Ala Pro Ala Thr Val Asn Ala Val Phe Asn 1 Asn Ser Asn Thr Val Val Asn Met Leu Ala Giu Gly Gly Ala Val Ala Ser Ala Leu Asp Thr 115 Asp Gly Leu 130 Ala Thr Gin 145 Pro Leu Thr Arg Asp Gly Thr Tyr Arg 195 Gi y Giu Val Ala Gin Asn 100 Gi y Ser Val Ala Ala 180 Ser 5 Phe Thr Gly Thr Leu Giu Leu Ser Ser Tyr 165 Ala Gly Ile Met Phe Thr 70 Ala Gly Gly Leu Asp 150 Val1 Thr Val Al a Asp Sex 55 Leu Asp Ala Sex Ser 135 Gly Pro Ile Asp Se r Thr 40 Thr Ser Gly Gin Ala 120 Al a Val1 Asp Ala Ser 200 Met 25 Glu Leu Asp Al a Sex 105 Ala Gly Gly Ile Sex 185 Ala Leu Phe Gi y GI y Val1 90 Leu Thr Thr Gin Asn 170 Gl u ValI Gi y Gi y Asp Val1 75 Thr Ala Gly Al a Leu 155 Sex Leu Ser Asn Val Gly Gly Leu Asp Ser Gin 140 Val1 Gin Sex Ala Gin Val Val Asn Arg Ile Val Asp Met Asn Gln Ala Ser Ala Asn Asp Arg Asp Gly Ile Giy Ala Ser Gin 110 Gin Thr Leu Ala 125 Leu Gly Gin Gly Asp Gin Val Ala 160 Le Ile Thr Leu 175 Asp Pro Ser Ser 190 Ser Gin Gin Leu 205 Ala Ala Gly Lea Gln Thr Leu Lys Asp Gly Ser Ser Gin Leu Ser Ile WO 01/00804 WO 0100804PCT[IBO0100922 Gly Ala 225 Glu Gin Leu Asp Ser Gin Pro Val 290 Gly Leu 305 Val Ala Arg Met Val Leu Leu Leu 370 Val Ala 385 Val Ala Phe Gin Ala Phe Asn Leu 450 Arg Phe 465 Leu Ala Lys Asp Arg Leu Glu Val 275 Glu Ala Trp Gly Gly 355 Asp Ile Gly Leu Phe 435 Val Ile Ile Tyr Thr Val1 Gly 260 Pro Thr Pro Met Gly 340 Leu Leu Ser Pro Val 420 His Arg Gin Ser His 500 Leu Val1 245 Ser Thr Giu Phe Ile 325 Phe Giy Asn T rp, Ser 405 Ser Trp Gin Ala Thr 485 Pro Aia 230 Gly Ser Phe Gin Phe 310 Leu Arg Gin Pro Val 390 Ala Ser Phe Met Ile 470 Leu Giu Asp Ala Giu Ala Ala 295 Met His Gly Ala Ala 375 Phe Gi y GI y His Ile 455 T rp A4la Leu Giy Gin Leu Asp 280 Gly Ala Pro Thr Th r 360 His Ile Arg Gly Thr 440 Phe Val1 Asn Lys Th r Ala Al a 265 Gi y Asp ValI Ile Leu 345 Ile Pro Se r Val1 Leu 425 Tyr Asn Leu Arg Val1 505 Ser Leu 250 Leu Ala Thr Gly Ser 330 Ala Met Aila Ile Leu 410 Tyr Asp Giu Leu Thr 490 Gin 235 Arg Lys Asp Thr Leu 315 Arg Ser Trp Giy Th r 395 Ser Pro Pro Thr Phe 475 As n Leu Asp Leu Thr Pro 300 Phe Arg Tyr Ala Leu 380 H is Ile Pro Ile Pro 460 Ile Lys Aia Aia Giy Thr Thr Asp 270 Thr Ile 285 Leu Phe Met Gly Ala Lou Leu Pro 350 Vai Lou 365 Trp Met Met Phe Val Met Giu Thr 430 Thr Tyr 445 Ser Asn Trp, Ala Val Leu WO 01/00804 <210> 293 <211> 664 <212> DNA <213> CorynebacteriUm glutamicum <220> <221> CDS <222> (664) <223> RXN01091 <400> 293 tcgtcggaaa aactggcgat actattgata. acgggcatgg PCT/IBOO/00922 gttcaccttC gataaagcac ggtctatqct ggactatcgC cttttgacac gagtatcgca atg gtc ccg aac aca.
Met Val Pro Asn Thr gtC Val1 ct g Leu tgg Trp gaa Gin cta Leu caa Gin gca Ala ca g Gin atc Ile ct t Len gaa Gin ga t Asp ggc Gly cgc Arg atg Met att Ile tcg Ser aaq Lys 135 atc Ile cat His att Ile tac Tyr ggC Gi y gcg Ala t cg Ser aac Asn 120 gcg Ala cat His atc Ile ga a Giu gag Giu gag Giu cgc Arg ga c Asp 105 gcg Aila ccc Pro gac Asp atg Met cag Gin gtt Val ttg Len gag Giu aag Lys aaa Lys gag Glu gaa Gin gcg Ala acc Thr gcc Ala ggc Gly 75 gca Ala a tg Met tcc Ser cgc Arg acc Thr tgc Cys ttt Phe gac Asp 60 ga t Asp ggc Gly gtt Val1 gcc Ala gcg Ala 140 gcc Ala ctg Leu gcc Al a 45 gcc Al a ttg Leu cat His ttg Leu ga c Asp 125 gg C Gly gat Asp cgc Arg 30 agc Se r ato Ile ctg Leu t tc Phe cgc Arg 110 cag Gin aaa Lys ctg Leu 15 ga t Asp a tc Ile gcg Ala ttt Phe gct Al a 95 cat His cag Gin gCg Ala gcg Ala ccg Pro gcg Ala cag Gin cag Gin 80 ttg Len ccg Pro gtg Val1 caa Gin 1 acg Thr gtC Val1
CCC
Pro gaa Giu acc Thr gtt Val1 cac His gaa Giu aag Lys 145 cag atc Gin Ile agc gga Ser Gly cac acg His Thr gac tgg Asp Trp gtg ttt Val Phe gac gtg Asp Val gtg ttc Val Phe 115 gat tgg Asp Trp 130 ggc gtt Giy Val cag Gin tgC Cys at t Ile
CCC
Pro ca c His gtg Val 100 ggc Gly gaa.
Gin t tg Leu C9g Arg ccg Pro gag Gin gag Gin gcc Ala aag Lys gcg Ala gtc Val1 ga t Asp 115 163 211 259 307 355 403 451 499 547 ggc gtc gcg Giy Val Ala 150 ctg gga ctg cct gcc ctg atg cgc gcg acg aag ctg caa Leu Gly Len Pro Ala Leu Met 155 Ala Thr Lys Leu Gin 165 WO 01/00804 PCT/IBOO/00922 aac aac gcc gcg cgc gtt ggg ttt gat tgg ccc gac att ggg cag gta 643 Asn Asn Ala Ala Arg Val Gly Phe Asp Trp Pro Asp Ile Gly Gin Vai 170 175 180 ctt qga aag gtg acc gag gaa 664 Leu Gly Lys Val Thr'Giu Glu 185 <210> 294 <211> 188 <212> PRT <2i3> Corynebacterium giutamicum <400> 294 Met Val Pro Asfl Thr Val Leu Ile 1 Thr Val1 Pro Glu Thr Val1 His Giu Lys 145 Ala Gin Ser His Asp ValI Asp Val Asp 130 Gi y Thr 5 Gin Arg Cys Pro Ile Giu Pro Giu His Ala Vai Lys 100 Gly Ala Giu Val Leu Asp Leu Gin 165 Leu Trp Giu Leu Gin Ala Gin Ilie Gi y 150 As n Glu Asp Giy Arg Met Ile Ser Lys 135 Vali Asn His Asp Ile Met 25 Giu Gin Giu Val Giu Leu Arg Giu 90 Asp Lys 105 Ala Lys Pro Giu Leu Gly Ala Arg 170 Glu Thr Ala Asp Leu Ala Leu Ala Al a Le u His Leu Asp 125 Gly Al a Phe Arg Se r Ile Leu Phe Arg 110 Gin Lys Leu Asp Asp Ile Ala Phe Ala His Gin Ala Met Trp 175 Asp Ile Gly Val Leu Gly Lys Val1 185 Thr Glu Giu <210> 295 <211> 357 <212> DNA <213) Corynebacterium giutainicum WO 01/00804 <220> <221> CDS <222> (334) <223> RXS02979 <400> 295 ctaggtcaag gaacttcact cggctagtcc ttz gcaccgtaag gcacgaaagt taccgaaagg act PCTIIBOO/00922 igactcaa atgtqttcag acaaacactg :ggttccc atq acc gcc cca aac Met Thr Ala Pro Asn 1 act ctc aag caa aca act ctt cgc tct gat gag ttc tct tgc cca. tcc Thr Leu Lys Gin Thr Thr Leu Arg Ser Asp Giu Phe Ser Cys Pro Ser 15 tgt gtc tcc aag att gaa aac aaa ttg aat gga ttg gat ggc gtc gac Cys Val Ser Lys Ilie Glu Asn Lys Leu Asn Gly Leu Asp Gly Val Asp 30 aat gca gag gtg aag ttc tcc tcc gga aga etc ctt gtt gat cac gac Asn Ala Glu Val Lys Phe Ser Ser Gly Arg Ile Leu Val Asp His Asp 45 ccc agc aag gtc tct aic aag gat cta gtc gct gca gtc gca gag gtt Pro Ser Lys Val Ser Ile Lys Asp Leu Val Ala Ala Val Ala Giu Val 60 ggc tac acc gca aag cca iCe gca atc taaaacictc agttagacca Gly Tyr Thr Ala Lys Pro Ser Ala Ile ta <210> 296 <211> 78 <212> PRT <213> Corynebacterium glutamicum <400> 296 Met Thr Ala Pro Asn Thr Leu Lys Gin Thr Thr Leu Arg Ser Asp Glu 1 5 10 Phe Ser Cys Pro Ser Cys Val Ser Lys Ile Glu Asn Lys Leu Asn Gly 25 Leu Asp Gly Val Asp Asn Ala Glu Val Lys Phe Ser Ser Gly Arg Ile 40 Leu Val Asp His Asp Pro Ser Lys Val Ser Ile Lys Asp Leu Val Ala 55 Ala Val Ala Glu Val Gly Tyr Thr Ala Lys Pro Ser Ala Ile 70 WO 01/00804 <210> 297 <211> 357 <212> DNA <213> Corynebacterium glutarnicum <220> <221> CDS <222> (101) (334) <223> RXS02987 <400> 297 gttgtttgat ccaggtcaag gaattaaccc ggaaaggacc acaggaacat gacgataaaa gatgaaagga cctqgttacg PCTIBOOIOO922 giatctttaa aggtgcaagc atg acc gcc ccc gcc 1 acq ctg aag aac acc acc ttg cgc tct gat gag ttc acc tgt ccg agc Thr Leu Lys Asn Thr Thr Leu Arg Ser Asp Glu Phe Thr Cys Pro Ser 15 tgt gtc gcc aag atc gaa aac aag ctg aat ggt ttg qac ggc gtg gag Cys Val Ala Lys Ile Giu Asn Lys Len Asn Gly Leu Asp Gly Val Gin 30 aat qcg gag gtg aag ttc tcc tcc gga cgc atc ctq atc acc cac gac Asn Ala Gin Val Lys Phe Ser Ser Gly Arg Ile Len Ile Thr His Asp 45 cca cag aag gtc tcc gta cgt gac ctg gtc acc gcg gta gcc gag gtc Pro Gin Lys Val Ser Val Arg Asp Len Val Thr Ala Val Ala Gin Val 60 ggt tat acc gcc aag ccg tcg gcg atc tgacgcactc ccgaccccac Gly Tyr Thr Ala Lys Pro Ser Ala Ile a ag <210> 298 <211> 78 <212> PRT <213> Coryriebacterillf giutamicum <400> 298 Met Thr Ala Pro Ala Thr Len Lys Asn Thr Thr Len Arg Ser Asp Giu 1 5 10 Phe Thr Cys Pro Ser Cys Val Ala Lys Ile Giu Asn Lys Len Asn Giy 25 Len Asp Gly Vai Gin Asn Ala Giu Val Lys Phe Ser Ser Gly Arg Ile 40 Len Ile Thr His Asp Pro Gin Lys Val Ser Val Arg Asp Len Val Thr 55 WO 01/00804 Ala Val Ala Glu Val Gly Tyr Thr Ala Lys Pro Ser Ala Ile 70 <210> 299 <211> 492, <212> DNA <213> Corynebacterium glutamicum <220> <221> CDS <222> (101)..(469) <223> RXS03095 <400> 299 aacgcctcaa ttagtgccag accttgccga ccgcagacca aacttcaccaI PCT/IBOO/00922 tttcaaacca tccctagcca caacaacggc agttgtgcaa tgatctgcgt atg aat gca gat aag Met Asn Ala Asp Lys aaa Lys ga a Giu gca Al a gi c Val1 atg Met aaa Lys cag Gin tgc gga Cys Gly ttc gga Phe Gly cga aac Arg Asn aaa tcc Lys Ser cga atc Arg Ile acc aat Thr Asn gaa cac Giu His 105 aac Asn ctc Leu ggt Gi y gca Ala t cc Ser 75 cac His at Ile ccg gat agc Pro Asp Ser gcg gac gcc Ala Asp Ala 30 gaa ctt tcc Glu Leu Ser 45 gca gtt tcc Ala Vai Ser acc cgt caa Thr Arg Gin gca tca cag Ala Ser Gin gcg gac ggc Ala Asp Gly 110 caa Gin act Thr gta Val1 caa Gin ga a Glu ct a Leu cag tac Tyr cga Arg aac As n cac His gg t Gly 80 gtc Val1 act 1 gtc Val1 gt t Val1 cac His ctc Leu caa Gin tcc Ser ccc ct Leu atc Ile 35 9g Ala cgg Arg qt t Val1 gct Al a ca c His 115 gt c Val1 tig Le u atc Ile cgc Arg tac Tyr tt Phe cac His 163 211 259 307 355 403 451 Gin Thr Pro Pro cga gaa Arg Giu cga gaa caa tca Arg Glu Gin Ser tgaccaccca cagtcaccaa gaa 120 <210> 300 <211> 123 WO 01/00804 <212> PRT <213> Corynebacterium giutamicum <400> 300 Met Asn Ala Asp Lys Lye Met 'Cys Gly 1 5 Val Giu Leu Ala Val Giu Val Phe Gly 25 Val Arg Ile Ile Leu Ala Leu Arg Asn 40 His Leu Ala A p Ile Val Asp Lys Ser 55 Leu Ala ArgLeu Arg Met Ala Ar Ile 70 Gin Arg Val Phe Tyr Lys Leu Thr Asn Ser Asp Ala Ile PP Gin Ala Giu His 100 105 Pro Pro His His His Arg Glu Arg Glu 115 120 PCT/IBOO/00922 Met Asn.Pro 10 Leu Leu Ala Ser Giy Giu Pro Ala Ala Val Ser Thr Giu His Ala 90 Thr Ile Ala Gin Ser Asp Ser Gin Asp Ala Thr Leu Ser Val Val Ser Gin Ah4 Gln Giu Ser Gin Leu Asp Gly &ln 110 <210> 301 <211> <212> PRT <213> Corynebacteri~m glutamicun <400> 3.01 Ala Pro Ala Leu Gly Pro Thr Leu Ser Gly 1 5 <210 302 <211> <21'2> PRT <213> Corynebacteriun giutamicum p00> 302 G1ly Xaa Xaa Xaa Gly Pro Xaa Xaa Gly Gly <210> 303 <211> 212> DNA <213> Corynebacteriun giutamicun <400> 30-3 ctccaggatt gctccgaagg WO 01/00804 PCT/IBOO/00922 <210> 304 <211> <212> DNA <213> Corynebacteriumr glutamicum <400> 304 cacagtggtt gaccactggc BGI-124CPPC 97

Claims (29)

1. An isolated Corynebacterium glutamicum nucleic acid molecule comprising the nucleotide sequence set forth in SEQ ID NO:1, or a complement thereof.
2. An isolated nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2, or a complement thereof.
3. An isolated nucleic acid molecule which encodes a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2, or a complement thereof.
4. An isolated nucleic acid molecule comprising a nucleotide sequence which 10 is functionally equivalent, and at least 50% identical, to the entire nucleotide sequence set forth in SEQ ID NO;1, or a complement thereof.
5. An isolated nucleic acid molecule comprising a fragment of at least contiguous nucleotides of the nucleotide sequence set forth in SEQ ID NO:1, or a complement thereof. 15 6. An isolated nucleic acid molecule comprising the nucleic acid molecule of any one of claims 1 to 5 and a nucleotide sequence encoding a heterologous polypeptide.
7. A vector comprising the nucleic acid molecule of any one of claims 1 to 6.
8. The vector of claim 7, which is an expression vector.
9. A host cell transfected with the expression vector of claim 8. The host cell of claim 9, wherein said cell is a microorganism.
11. The host cell of claim 10, wherein said cell belongs to the genus Corynebacterium or Brevibacterium. COMS ID No: SBMI-01718905 Received by IP Australia: Time 12:10 Date 2005-10-12 12/10 '05 WED 12:03 FAX 61 2 9888 7600 WATERMARK 0008 105
12. The host cell of claim 9, wherein the expression of said nucleic acid molecule results in the modulation in production of a fine chemical from said cell.
13. The host cell of claim 12, wherein said fine chemical is selected from the group consisting of: organic acids, proteinogenic and nonproteinogenic amino acids, purine and pyrimidine bases, nucleosides, nucleotides, lipids, saturated and unsaturated fatty acids, diols, carbohydrates, aromatic compounds, vitamins, cofactors, polyketides, and enzymes.
14. A method of producing a polypeptide comprising culturing the host cell of claim 9 in an appropriate culture medium to, thereby, produce the polypeptide. 10 15. An isolated polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2. o 9
16. An isolated polypeptide comprising a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2.
17. An isolated polypeptide which is encoded by a nucleic acid molecule 15 comprising a nucleotide sequence which is functionally equivalent, and at least identical, to the entire nucleotide sequence set forth in SEQ ID NO:1, wherein said polypeptide has lincomycine resistance protein activity.
18. An isolated polypeptide comprising an amino acid sequence which is functionally equivalent, and at least 50% identical, to the entire amino acid sequence set forth in SEQ ID NO:2.
19. An isolated polypeptide comprising a fragment of a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2, wherein said polypeptide fragment maintains a biological activity of the polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2.
20. The isolated polypeptide of any one of claims 15 to 20, further comprising heterologous amino acid sequences. COMS ID No: SBMI-01718905 Received by IP Australia: Time 12:10 Date 2005-10-12 12/10 '05 WED 12:04 FAX 61 2 9888 7600 WATERMARK 141009 106
21. A method for producing a fine chemical, comprising culturing the cell of claim 9 such that the fine chemical is produced.
22. The method of claim 21, wherein said method further comprises the step of recovering the fine chemical from said culture.
23. The method of claim 21, wherein said cell belongs to the genus Corynebacterfum or Brevibacterlum.
24. The method of claim 21, whereIn said cell is selected from the group consisting of: Cotynebacterium glutamicum, Corynebacterium herculis, Corynebacterium, lilium, Corynebacterium acetoacidophilum, Cotynebacterium acetoglutamicum, Corynebacterium acetophilum, Corynebacterium ammoniagenes, Corynebacterium fujiokense, Corynebacterium nitrilophilus, Brevibacterium ammoniagenes, Brevibacterium butanicum, Brevibacterium divaricatum, Brevibacteiurn flavum, Brevibacterlum healii, Brevibacterium ketoglutamicum, Brevibacterium ketosoreductum, Brevibacterium lactofermentum, Brevibacterium linens, Brevibacterium paraffinolyticum, and Sthose strains set forth in Table 3. The method of claim 21, wherein expression of the nucleic acid molecule from said vector results in modulation of production of said fine chemical.
26. The method of claim 21, wherein said fine chemical is selected from the 20 group consisting of: organic acids, proteinogenic and nonproteinogenic amino acids, purine and pyrimidine bases, nucleosides, nucleotides, lipids, saturated and unsaturated fatty acids, diols, carbohydrates, aromatic compounds, vitamins, cofactors, polyketides and enzymes.
27. The method of claim 21, wherein said fine chemical is an amino acid.
28. The method of claim 27, wherein said amino acid is drawn from the group consisting of: lysine, glutamate, glutamine, alanine, aspartate, glycine, serine, COMS ID No: SBMI-01718905 Received by IP Australia: Time 12:10 Date 2005-10-12 12/10 '05 WED 12:04 FAX 81 2 9888 7600 WATERMARK 107 threonine, methionine, cysteine, valine, leucine, isoleucine, arginine, proline, histidine, tyrosine, phenylalanine, and tryptophan.
29. A method for producing a fine chemical, comprising culturing a cell whose genomic DNA has been altered by the introduction of a nucleic acid molecule of any one of claims 1 to 6. A method of detecting the presence or activity of Corynebacterium diphtheriae in a subject, the method comprising detecting the presence of at least one of the nucleic acid molecules of any one of claims 1 to 5 or the polypeptide molecules of any one of claims 15 to 20 In the subject, thereby detecting the presence or activity of Corynebacterium diphtheriae in the subject.
31. A host cell comprising a nucleic acid molecule comprising the nucleotide sequence set forth in SEQ ID NO:1, wherein the nucleic acid molecule is disrupted.
32. A host cell comprising a nucleic acid molecule comprising the nucleotide sequence set forth in SEQ ID NO:1, wherein the nucleic acid molecule comprises one or more nucleic acid modifications as compared to the nucleotide sequence set forth in SEQ ID NO:1.
33. A host cell comprising a nucleic acid molecule comprising the nucleotide sequence set forth In SEQ ID NO:1, wherein the regulatory region of the nucleic 20 acid molecule is modified relative to the wild-type regulatory region of the molecule.
34. A polypeptide produced by the method of claim 14. COMS ID No: SBMI-01718905 Received by IP Australia: Time 12:10 Date 2005-10-12 12/10 '05 WED 12:04 FAX 61 2 9888 7600 WATERMARK 1~011 108 Aftine chemical produced by a method of any one of claims 21 to 29. DATED this 1 2th day of October 2005 BASF AKTIENGESELLSCHAFT WATERMARK PATENT TRADE MARK ATTORNEYS 290 BURWOOIJ ROAD HAWTHORN VICTORIA 3122 AUSTRALIA P20692AUOO COMS ID No: SBMI-01718905 Received by 1P Australia: Time 12:10 Date 2005-10-12
AU58369/00A 1999-06-25 2000-06-23 Corynebacterium glutamicum genes encoding stress, resistance and tolerance proteins Ceased AU783703B2 (en)

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AU2006200801A AU2006200801A1 (en) 1999-06-25 2006-02-24 Corynebacterium glutamicum genes encoding stress, resistance and tolerance proteins

Applications Claiming Priority (25)

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US14103199P 1999-06-25 1999-06-25
US60/141031 1999-06-25
US14269299P 1999-07-01 1999-07-01
DE19930429 1999-07-01
DE19930429 1999-07-01
US60/142692 1999-07-01
DE19931457 1999-07-08
DE19931457 1999-07-08
DE19931413 1999-07-08
DE19931541 1999-07-08
DE19931413 1999-07-08
DE19931541 1999-07-08
DE19932209 1999-07-09
DE19932230 1999-07-09
DE19932230 1999-07-09
DE19932209 1999-07-09
DE19932914 1999-07-14
DE19932914 1999-07-14
US15121499P 1999-08-27 1999-08-27
DE19940764 1999-08-27
DE19940764 1999-08-27
US60/151214 1999-08-27
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DE19941382 1999-08-31
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RU2019128538A (en) 2018-09-26 2021-03-11 Эвоник Оперейшенс ГмбХ METHOD FOR ENZYMATIC PRODUCTION OF L-LYSINE
CN111088202B (en) * 2019-12-25 2022-01-04 南京工业大学 Recombinant corynebacterium glutamicum for producing lysine through biological film-forming continuous fermentation and construction method thereof
CN111909912B (en) * 2020-09-11 2022-03-08 四川农业大学 MAP3K-19 gene for improving high-temperature tolerance of rice in heading stage, protein obtained by encoding same and application thereof
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