AU2008202554A1 - Novel genes encoding novel proteolytic enzymes - Google Patents

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AUSTRALIA

Patents Act COMPLETE SPECIFICATION

(ORIGINAL)

Class Int. Class Application Number: Lodged: Complete Specification Lodged: Accepted: Published: Priority Related Art: Name of Applicant: DSM IP Assets B.V.

Actual Inventor(s): Luppo Edens, Albertus Alard Dijk Van, Philipp Krubasik, Kaj Albermann, Alex Stock, Erik Kimpel, Sabine Klugbauer, Christian Wagner, Andreas Fritz, Wilk Gustedt Von, Oliver Heinrich, Dieter Maier, Fabio Spreafico, Ulrike Folkers, Sylvia Hopper, Wolfram Kemmner, Pamela Tan, Josephine Stiebler, Richard Albang Address for Service and Correspondence: PHILLIPS ORMONDE FITZPATRICK Patent and Trade Mark Attorneys 367 Collins Street Melbourne 3000 AUSTRALIA Invention Title: NOVEL GENES ENCODING NOVEL PROTEOLYTIC ENZYMES Our Ref 831117 POF Code: 223028/464219 The following statement is a full description of this invention, including the best method of performing it known to applicant(s): -1- 60O6q 00

O

O NOVEL GENES ENCODING NOVEL PROTEOLYTIC ENZYMES The present application is a divisional application from Australian patent application S number 2006723, itself a divisional of Australian Patent Application number 2002308306, the entire disclosures of both of which are incorporated herein by reference.

V Field of the invention 00 The invention relates to newly identified sequences comprising genes that encode novel proteases isolated from Aspergillus niger. The invention features the full length nucleotide sequence of the novel genes, the sequences comprising the full length coding sequences of the novel proteases as well as the amino acid sequences of the full-length functional proteins and fragments and variants thereof. The invention also relates to methods of using these enzymes in industrial processes and methods of diagnosing fungal infections.

Also included in the invention are cells transformed with a polynucleotide according to the invention and cells wherein a protease according to the invention is genetically modified to enhance or reduce its activity and/or level of expression.

Background of the invention Proteolytic Enzymes Proteins can be regarded hetero-polymers that consist of amino acid building blocks connected by a peptide bond. The repetitive unit in proteins is the central alpha carbon atom with an amino group and a carboxyl group. Except for glycine, a so-called amino acid side chain substitutes one of the two remaining alpha carbon hydrogen atoms. The amino acid side chain renders the central alpha carbon asymmetric. In general, in proteins the L-enantiomer of the amino acid is found. The following terms describe the various types of polymerized amino acids. Peptides are short chains of amino acid residues with defined sequence. Although there is not really a maximum to the number of residues, the term usually indicates a chain which properties are mainly determined by its amino acid composition and which does not have a fixed three-dimensional conformation. The term polypeptide is usually used for the longer chains, usually of defined sequence and length and in principle of the appropriate length to fold into a three-dimensional structure. Protein is reserved for polypeptides that occur naturally and exhibit a defined three-dimensional structure. In 35 case the proteins main function is to catalyze a chemical reaction it usually is called an enzyme. Proteases are the U:VanjIFLESMAU PMS%?7831%Di sL na!77633.amenen aMe 1A.30.05.08.adc 00 enzymes that catalyze the hydrolysis of the peptide bond in (poly)peptides and Sproteins.

SUnder physiological conditions proteases catalyse the hydrolysis of the peptide bond.

5 The International Union of Biochemistry and Molecular Biology (1984) has recommended to use the term peptidase for the subset of peptide bond hydrolases (Subclass E.C The terms protease and peptide hydrolase are synonymous with peptidase and may also be used here. Proteases comprise two classes of enzymes: 0the endo-peptidases and the exo-peptidases, which cleave peptide bonds at points 00 10 within the protein and remove amino acids sequentially from either N or C-terminus Srespectively. Proteinase is used as a synonym for endo-peptidase. The peptide bond may occur in the context of di-, tri-, tetra-peptides, peptides, polypeptides or proteins. In general the amino acid composition of natural peptides and polypeptides comprises different amino acids, which exhibit the L-configuration (except for glycine which does not have a chiral centre). However the proteolytic activity of proteases is not limited to peptides that contain only the 20 natural amino acids. Peptide bonds between so-called non-natural amino acids can be cleaved too, as well as peptide bonds between modified amino acids or amino acid analogues. Some proteases do accept D enantiomers of amino acids at certain positions. In general the remarkable stereoselectivity of proteases makes them very useful in the process of chemical resolution.

Many proteases exhibit interesting side activities such as esterase activity, thiol esterase activity and (de)amidase activity. These side activities are usually not limited to amino acids only and might turn out to be very useful in bioconversions in the area of fine chemicals.

There are a number of reasons why proteases of filamentous fungi, eukaryotic microorganisms, are of particular interest. The basic process of hydrolytic cleavage of peptide bonds in proteins appears costly and potentially detrimental to an organism if not properly controlled. The desired limits to proteolytic action are achieved through the specificity of proteinases, by compartmentalization of proteases and substrates within the cell, through modification of the substrates allowing recognition by the respective proteases, by regulation via zymogen activation, and the presence or absence of specific inhibitors, as well through the regulation of protease gene expression. In fungi, proteases are also involved in other fundamental cellular processes, including intracellular protein turnover, processing, translocation, sporulation, germination and differentiation. In fact, Aspergillus nidulans and Neurospora crassa have been used as model organisms for rL L1 rULI I lL 4 00 analyzing the molecular basis of a range of physiological and developmental processes.

CN Their genetics enable direct access to biochemical and genetical studies, under defined nutrient and cultivation conditions. Furthermore, a large group of fungi pathogenic to Shumans, live-stock and crop, has been isolated and proteolysis has been suggested to play a role in their pathogenicity (host penetration, countering host defense mechanisms and/or nutrition during infection). Proteases are also frequently used in laboratory, clinical I and industrial processes; both microbial and non-microbial proteases are widely used in.

the food industry (baking, brewing, cheese manufacturing, meat tenderizing), in tanning industry and in the manufacture of biological detergents (Aunstrup, 1980). The 00 10 commercial interest in exploiting certain filamentous fungi, especially the Aspergilli, as hosts for the production of both homologous and heterologous proteins, has also recently renewed interests in fungal proteases (van Brunt, 1986ab). Proteases often cause problems in heterologous expression and homologous overexpression of proteins in fungi. In particular, heterologous expression is hampered by the proteolytic degradation of the expressed products by homologous proteases. These commercial interests have resulted in detailed studies of proteolytic spectra and construction of protease deficient strains and have improved the knowledge about protease expression and regulation in these organisms. Consequently there is a great need to identify and eliminate novel proteases in filamentous fungi.

Micro-organisms such as for example fungi are particularly useful in the large scale production of proteins. In particular when such proteins are secreted into the medium.

Proteolytic enzymes play a role in these production processes. On the one hand particular proteolytic enzymes are in general required for proper processing of the target protein and the metabolic well-being of the production host. On the other hand proteolytic degradation may significantly decrease the yield of secreted proteins. Poor folding in the secretion pathway may lead to degradation by intracellular proteases.

This might be a particular problem with producing heterologous proteins. The details of the proteolytic processes, which are responsible for the degradation of the proteins that are diverted from the secretory process in fungi are not exactly known. In eukaryotes the degradation of cellular proteins is achieved by a proteasome and usually involves ubiquitin labelling of proteins to be degraded. In fungi, proteasomal and vacuolar proteases are also likely candidates for the proteolytic degradation of poorly folded secretory proteins. The proteolytic degradation is likely cytoplasmic, but endoplamatic reticulum resident proteases cannot be excluded. From the aspect of production host strain improvement the proteolytic system may be an interesting target for genetic 00 0 engineering and production strain improvement. Additional copies of protease genes, Sover-expression of certain proteases, modification of transcriptional control, as well as Sknock out procedures for deletion of protease genes may provide a more detailed Sinsight in the function a given protease. Deletion of protease encoding genes can be a valuable strategy for host strain improvement in order to improve production yield for homologous as well as heterologous proteins.

V' Eukaryotic microbial proteases have been reviewed by North (1982). More recently, Suarez Rendueles and Wolf (1988) have reviewed the S. cerevisiae proteases and their 00 10 function.

Apart from the hydrolytic cleavage of bonds, proteases may also be applied in the formation of bonds. Bonds in this aspect comprise not only peptide and amide bonds but also ester bonds. Whether a protease catalyses the cleavage or the formation of a particular bond does in the first place depend on the thermodynamics of the reaction.

An enzyme such as a protease does not affect the equilibrium of the reaction. The equilibrium is dependent on the particular conditions under which the reaction occurs.

Under physiological conditions the thermodynamics of the reactions is in favour of the hydrolysis of the peptide due to the thermodynamically very stable structure of the zwitterionic product. By application of physical-chemical principles to influence the equilibrium, or by manipulating the concentrations or the nature of the reactants and products, or by exploiting the kinetic parameters of the enzyme reaction it is possible to apply proteases for the purpose of synthesis of peptide bonds. The addition of water miscible organic solvents decreases the extent of ionisation of the carboxyl component, thereby increasing the concentration of substrate available for the reaction. Biphasic systems, water mimetics, reverse micelles, anhydrous media, or modified amino and carboxyl groups to invoke precipitation of products are often employed to improve yields. When the proteases with the right properties aie available the application of proteases for synthesis offers substantial advantages. As proteases are stereoselective as well as regio-selective, sensitive groups on the reactants do usually not need protection and reactants do not need to be optically pure. As conditions of enzymatic synthesis are mild, racemization and decomposition of labile reactants or products can be prevented. Apart from bonds between amino acids, also other compounds exhibiting a primary amino group, a thiol group or a carboxyl group may be linked by properly selected proteases. In addition esters, thiol esters and amides may be synthesized by certain proteases. Protease have been shown to exhibit 00 O regioselectively in the acylation of mono, di- and tri- saccharides, nucleosides, and N riboflavin. Problems with stability under the sometimes harsh reaction conditions may be prevented by proper formulation. Encapsulation and immobilisation do not only stabilise enzymes but also allow easy recovery and separation from the reaction medium. Extensive crosslinking, treatment with aldehydes or covering the surface with certain polymers such as dextrans, polyethyleneglycol, polyimines may substantially extend the lifetime of the biocatalyst.

SThe Natural Roles of Proteases 0 0 10 Traditionally, proteases have been regarded as degrading enzymes, capable of cleaving O proteins into small peptides and/or amino acids, and whose role it is to digest nutrient protein or to participate in the turnover of cellular proteins. In addition, it has been shown that proteases also play key roles in a wide range of cellular processes, via mechanisms of selective modification by limited proteolysis, and thus can have essential regulatory functions (Holzer and Tschensche 1979; Holzer and Heinrich, 1980). The specificity of a proteinase is assumed to be closely related to its physiological function and its mode of expression. With respect to the function of a particular protease, its localisation is often very important; for example, a lot of the vacuolar and periplasmic proteases are involved in protein degradation, while many of the membrane-bound proteases are important in protein processing (Suarez Rendueles and Wolf, 1988). The different roles of proteases in many cellular processes can be divided into four main functions of proteases: 1) protein degradation, 2) posttranslational processing and (in)activation of specific proteins, 3) morphogenesis, and 4) pathogenesis.

An obvious role for proteases in organisms which utilise protein as a nutrient source is in the hydrolysis of nutrients. In fungi, this would involve the degradation outside the cells by extracellular broad specificity proteases. Protein degradation is also important for rapid turnover of cellular proteins and allows the cell to remove abnormal proteins and to adapt their complement of protein to changing physiological conditions. Generally, proteases of rather broad specificity should be extremely well-controlled in order to protect the cell from random degradation of other than correct target proteins.

Contrary to the hydrolysis the synthesis of polypeptides occurs in vivo by an ATP driven process on the ribosome. Ultimately the sequence in which the amino acids are linked is dictated by the information derived from the genome. This process is known as the transcription. Primary translation products are often longer than the final functional 00 O products, and after the transcription usually further processing of such precursor C proteins by proteases is required. Proteases play a key role in the maturation of such Sprecursor proteins to obtain the final functional protein. In contrast to the very controlled trimming and reshaping of proteins, proteases can also be very destructive and may completely degrade polypeptides into peptides and amino acids. In order to avoid that proteolytic activity is unleashed before it is required, proteases are subject to extensive regulation. Many proteases are synthesized as larger precursors known as zymogens, Swhich become activated when required. Remarkably this activation always occurs by Sproteolysis. Apart from direct involvement in the processing, selective activation and 00 10 inactivation of individual proteins are well-known phenomena catalyzed by specific 0 proteases.

The selectivety of limited proteolysis appears to reside more directly in the proteinasesubstrate interaction. Specificity may be derived from the proteolytic enzyme which recognizes only specific amino acid target sequences. On the other hand, it may also be the result of selective exposure of the 'processing site' under certain conditions such as pH, ionic strength or secondary modifications, thus allowing an otherwise non-specific protease to catalyze a highly specific event. The activation of vacuolar zymogens by limited proteolysis gives an example of the latter kind.

Morphogenesis or differentiation can be defined as a regulated series of events leading to changes from one state to another in an organism. Although direct relationships between proteases and morphological effects could not be established in many cases, the present evidence suggests a significar* involvement of proteases in fungal morphogenesis; apart form the observed extensive protein turnover during differentiation, sporulation and spore germination, proteases are thought to be directly involved in normal processes as hyphal tip branching and septum formation, (Deshpande, 1992).

Species of Aspergillus, in particular A. fumigatus and A. flavus, have been implicated as the causative agents of a number of diseases in humans and animals called aspergillosis (Bodey and Vartivarian, 1989). It has been repeatedly suggested that proteases are involved in virulence of A. fumigatus and A. flavus like there are many studies linking secreted proteases and virulence of bacteria. In fact, most human infections due to Aspergillus species are characterised by an extensive degradation of the parenchyma of the lung which is mainly composed of collagen and elastin (Campbell et al., 1994).

Research has been focussed on the putative role of the secreted proteases in virulence S7 00 0 of A. fumigatus and A. flavus which are the main human pathogens and are known to Ng possess elastinolytic and collagenic activities (Kolattukudy et al., 1993). These Selastinolytic activities were shown to correlate in vitro with infectivity in mice (Kothary et Sal., 1984). Two secreted proteases are known to be produced by A. fumigatus and A.

flavus, an alkaline serine protease (ALP) and a neutral metallo protease (MEP). In A.

fumigatus both the genes encoding these proteases were isolated, characterised and disrupted (Reicherd et al., 1990; Tang et al, 1992, 1993; Jaton-Ogay et al., 1994).

However, alp mep double mutants showed no differences in pathogenecity when Scompared with wild type strains. Therefore, it must be concluded that the secreted A.

00 10 fumigatus proteases identified in vitro are not essential factors for the invasion of tissue 0 (Jaton Ogay et al., 1994). Although A. fumigatus accounts for only a small proportion of the airborne mould spores, it is the most frequently isolated fungus from lung and sputem (Schmitt et al., 1991). Other explanations for the virulence of the fungus could be that the conditions in the bronchia (temperature and nutrients) are favourable for the parasitic growth of A. fumigatus. As a consequence, invasive apergillosis could be a circumstancial event, when the host pathogenic defences have been weakened by immunosuppressive treatments or diseases like AIDS.

Four major classes of proteases are known and are designated by the principal functional groups in their active site: the 'serine', the 'thiol' or 'cysteine', the 'aspartic' or 'carboxyl' and the 'metallo' proteases. A detailed state of the art review on these major classes of proteases, minor classes and unclassified proteases can be found in Methods in Enzymology part 244 and 248 (A.J.Barrett ed, 1994 and 1995).

Specificity of Proteases Apart from the catalytic machinery of proteases another important aspect of proteolytic enzymes is the specificity of proteases. The specificity of a protease indicates which substrates the protease is likely to hydrolyze. The twenty natural amino acids offer a large number of possibilities to make up peptides. Eg with twenty amino acids one can make up already 400 dipeptides and 800 different tripeptide, and so on. With longer peptides the number of possibilities will become almost unlimited. Certain proteases hydrolyze only particular sequences at a very specific position. The interaction of the protease with the peptide substrate may encompass one up to ten amino acid residues of the peptide substrate. With large proteinacious substrates there may be even more residues of the substrate that interact with the proteases. However this likely involves less specific interactions with protease residues outside the active site binding cleft. In 00 0 general the specific recognition is restricted to the linear peptide, which is bound in the C active site of the protease.

SThe nomenclature to describe the interaction of a substrate with a protease has been introduced in 1967 by Schechter and Berger (Biochem. Biophys. Res. Com., 1967, 27, 157-162) and is now widely used in the literature. In this system, it is considered that the amino acid residues of the polypeptide substrate bind to so-called sub-sites in the v active site. By convention, these sub-sites on the protease are called S (for sub-sites) Sand the corresponding amino acid residues are called P (for peptide). The amino acid 00 10 residues of the N-terminal side of the scissile bond are numbered P3, P2, P1 and those 0 residues of the C-terminal side are numbered P1', P2', P3'. The P1 or P1' residues are the amino acid residues located near the scissile bond. The substrate residues around the cleavage site can then be numbered up to P8. The corresponding sub-sites on the protease that complement the substrate binding residues are numbered S3, S2, S1, S1', S2', S3', etc, etc. The preferences of the sub-sites in the peptide binding site determine the preference of the protease for cleaving certain specific amino acid sequences at a particular spot. The amino acid sequence of the substrate should conform with the preferences exhibited by the sub-sites. The specificity towards a certain substrate is clearly dependant both on the binding affinity for the substrate and on the velocity at which subsequently the scissile bond is hydrolysed. Therefore the specificity of a protease for a certain substrate is usually indicated by its kcat/Km ratio, better known as the specificity constant. In this specificity constant kcat represents the turn-over rate and Km is the dissociation constant.

Apart from amino acid residues involved in catalysis and binding, proteases contain many other essential amino acid residues. Some residues are critical in folding, some residues maintain the overall three dimensional architecture of the protease, some residues may be involved in regulation of the proteolytic activity and some residue may target the protease for a particular location. Many proteases contain outside the active site one or more binding sites for metal ions. These metal ions often play a role in stabilizing the structure. In addition secreted eukaryotic microbial proteases may be extensively glycosylated. Both N- and O-linked glycosylation occurs. Glycosylation may aid protein folding, may increase solubility, prevent aggregation and as such stabilize the mature protein. In addition the extent of glycosylation may influence secretion as well as water binding by the protein.

0 Regulation of Proteolytic Activity A substantial number of proteases are subject to extensive regulation of the proteolytic activity in order to avoid undesired proteolytic damage. To a certain extent this Sregulation takes place at transcription level. For example in fungi the transcription of 5 secreted protease genes appears to be sensitive to external carbon and nitrogen sources, whereas genes encoding intracellular proteases are insensitive. The extracellular pH is sensed by fungi and some genes are regulated by pH. In this Sprocess transcriptional regulator proteins play a crucial role. Proteolytic processing of O such regulator proteins is often the switch that turns the regulator proteins either on or 00 10 off.

Proteases are subject to intra- as well as intermolecular regulation. This implies certain amino acids in the proteolytic enzyme molecule that are essential for such regulation.

Proteases are typically synthesized as larger precursors known as zymogens, which are catalytically inactive. Usually the peptide chain extension rendering the precursor protease inactive is located at the amino terminus of the protease. The precursor is better known as pro-protein. As many of the proteases processed in this way are secreted from the cells they contain in addition a signal sequence (pre sequence) so that the complete precursor is synthesized as a pre-pro-protein. Apart from rendering the protease inactive the pro-peptide often is essential for mediating productive folding.

Examples of proteases include serine proteases (alpha lytic protease, subtilisin, aqualysin, prohormone convertase), thiol proteases (cathepsin L and cruzian), aspartic proteases (proteinase A and cathepsin D) and metalloproteases. In addition the propeptide might play a role in cellular transpert either alone or in conjunction with signal peptides. It may facilitate interaction with cellular chaperones or it may facilitate transport over the membrane. The size of the extension in the precursor pre-proprotein may vary substantially, ranging from a short peptide fragment to a polypeptide, which can exist as an autonomous folding unit. In particular these larger extensions are often observed to be strong inhibitors of the protease even after cleavage from the protease. It was observed that even after cleavage such pro-peptides could assist in proper folding of the proteases. As such pro-peptides can be considered to function as molecular chaperones and separate or additional co-expression of such pro-peptides could be advantageous for protease production.

There is substantial difference in the level of regulation between proteases that are secreted into the medium and proteases that remain intracellular. Proteases secreted 00 into the medium are usually after activation no longer subject to control and therefore Sare usually relatively simple in their molecular architecture consisting of one globular Smodule. Intracellular proteases are necessarily subject to continuous control in order to Savoid damage to the cells. In contrast with zymogens of secreted proteases in more complex regulatory proteases very large polypeptide segments may be inserted between the signal and the zymogen activation domain of the proteolytic module.

Structure-function studies indicate that such non-protease parts may be involved in interactions with macroscopic structures, membranes, cofactors, substrates, effectors, inhibitors, ions, that regulate activity and activation of the proteolytic module(s) or its 00 10 (their) zymogens. The non-proteolytic modules exhibit remarkable variation in size and structure. Many of the modules can exist as such independently from the proteolytic module. Therefore such modules can be considered to correspond to independent structural and functional units that are autonomous with respect to folding. The value of such a modular organization is that acquisition of new modules can endow the recipient protease with new novel binding specificities and can lead to dramatic changes in its activity, regulation and targeting. The principle of modular organized proteolytic enzymes may also be exploited by applying molecular biology tools in order to create novel interactions, regulation, specificity, and/or targeting by shuffling of modules.

Although in general such additional modules are observed as N or C terminal extension, also large insertions within the exterior loops of the catalytic domain have been observed. It is believed that also in this case the principal fold of the protease represents still the essential topology to form a functional proteolytic entity and that the insertion can be regarded as substructure folded onto the surface of the proteolytic module.

Molecular Structure In principle the modular organization of larger proteins is a general theme in nature. In particular within the larger multimodular frameworks typical proteolytic modules show sizes of 100 to 400 amino acids on the average. This corresponds with the average size of most of the globular proteolytic enzymes that are secreted into the medium. As discussed above polypeptide modules are polypeptide fragments, which can fold and function as independent entities. Another term for such modules is domains. However domain is used in a broader context than module. The term domain as used herein refers usually to a part of the polypeptide chain that depicts in the three-dimensional structure a typical folding topology. In a protein domains interact to varying extents, but less extensively than do the structural elements within domains. Other terms such as .V V u

V.

P

~~Y1 vrr vr, vr ]1 00 O subdomain and folding unit are also used in literature. As such it is observed that many Sproteins that share a particular functionality may share the same domains. Such domains can be recognized from the primary structure that may show certain sequence

;Z

Spatterns, which are typical for a particular domain. Typical examples are the mononucleotide binding fold, cellulose binding domains, helix-turn-helix DNA binding motif, zinc fingers, EF hands, membrane anchors. Modules refer to those domains Swhich are expected to be able to fold and function autonomously. A person skilled in the art knows how to identify particular domains in a primary structure by applying commonly available computersoftware to said structure and homologous sequences 00 10 from other organisms or species.

Although multimodular or multidomain proteins may appear as a string of beads, assemblies of substantial more complex architecture have been observed. In case the various beads reside on the same polypeptide chain the beads are generally called modules or domains. When the beads do not reside on one and same polypeptide chain but form assemblies via non-covalent interactions then the term subunit is used to designate the bead. Subunits may be transcribed by one and the same gene or by different genes. The multi-modular protein may become proteolytically processed after transcription leading to multiple subunits. Individual subunits may consist of multiple domains. Typically the smaller globular proteins of 100-300 amino acids usually consist only of one domain.

Molecular Classification of Proteolytic Enzymes In general proteases are classified according to their molecular properties or according to their functional properties. The molecular classification is based on the primary structure of the protease. The primary structure of a protein represents its amino acid sequence, which can be derived from the nucleotide sequence of the corresponding gene. Tracing extensively the similarities in the primary structures may allow for the notice of similarities in catalytic mechanism and other properties, which even may extend to functional properties. The term family is used to describe a group of proteases that show evolutionary relationship based on similarity between their primary structures. The members of such a family are believed to have arisen by divergent evolution from the same ancestor. Within a family further sub-grouping of the primary structures based on more detailed refinement of sequence comparisons results in V VIUVUUVSJ.,J 12 00 O subfamilies. Classification according to three-dimensional fold of the proteases may N comprise secondary structure, tertiary structure and quarternary structure. In general Sthe classification on secondary structure is limited to content and gross orientation of Ssecondary structure elements. Similarities in tertiary structure have led to the recognition of superfamilies or clans. A superfamily or a clan is a group of families that are thought to have common ancestry as they show a common 3-dimensional fold. In general tertiary structure is more conserved than the primary structure. As a consequence similarity of the primary structure does not always reflect similar Sfunctional properties. In fact functional properties may have diverged substantially 00 10 resulting in interesting new properties. At present quarternary structure has not been 0 applied to classify various proteases. This might be due to a certain bias of the structural databases towards simple globular proteases. Many proteolytic systems that are subject to activation, regulation, or complex reaction cascades are likely to consist of multiple domains or subunits. General themes in the structural organization of such protease systems may lead to new types of classification.

Classification according to specificity.

In absence of sequence information proteases haven been subject to various type of functional classification. The classification and naming of enzymes by reference to the reactions which are catalyzed is a general principle in enzyme nomenclature. This approach is also the underlying principle of the EC numbering of enzymes (Enzyme Nomenclature 1992 Academic Press, Orlando). Two types of proteases (EC 3.4) can be recognized within Enzyme Nomenclature 1992, those of the exo-peptidases (EC 3.4.11-19) and those of the endo-peptidases (EC 3.4.21-24, 3.4.99). Endo-peptidases cleave peptide bonds in the inner regions of the peptide chain, away from the termini.

Exo-peptidases cleave only residues from the ends of the peptide chain. The exopeptidases acting at the free N-terminus may liberate a single amino acid residue, a dipeptide or a tripeptide and are called respectively amino peptidases (EC 3.4.11), dipeptidyl peptidases (EC 3.4.14) and tripeptidyl peptidase (EC 3.3.14). Proteases starting peptide processing from the carboxyl terminus liberating a single amino acid are called carboxy peptidase (EC 3.4.16-18). Peptidyl-dipeptidases (EC 3.4.15) remove a dipeptide from the carboxyl terminus. Exo- and endo-peptidase in one are the dipeptidases (EC 3.4.13), which cleave specifically only dipeptides in their two amino acid halves. Omega peptidases (EC 3.4.19) remove terminal residues that are either substituted, cyclic, or linked by isopeptide bonds 13 0 Apart from the position where the protease cleaves a peptide chain, for each type of protease a further division is possible based on the nature of the preferred amino acid C residues in the substrate. In general one can distinguish proteases with broad, medium Sand narrow specificity. Some proteases are simply named after the specific proteins or S 5 polypeptides that they hydrolyze, e.g. keratinase, collagenase, elastase. A narrow specificity may pin down to one particular amino acid or one particular sequence which is removed or which is cleaved respectively. When the protease shows a particular Spreference for one aminoacid in the P1 or Pl' position the name of this amino acid may O be a qualifier. For example prolyl amino peptidase removes proline from the amino 00 10 terminus of a peptide (proline is the P1 residue). X-Pro or proline is used when the 0bond on the imino side of the proline is cleaved (proline is P1' residue), eg proline carboxypeptidase removes proline from the carboxyl terminus. Prolyl endopeptidase (or Pro-X) cleaves behind proline while proline endopeptidase (X-Pro) cleaves in front of a proline. Amino acid residue in front of the scissile peptide bond refers to the amino acid residue that contributes the carboxyl group to the peptide bond.The amino acids residue behind the scissile peptide bond refers to the amino acid residue that contributes the amino group to the peptide bond. According to the general convention an amino acid chain runs from amino terminus (the start) to the carboxyl terminus (the end) and is numbered accordingly. Endo proteases may also show clear preference for a particular amino acid in the P1 or P1'position, eg glycyl endopeptidase, pepiidyllysine endopeptidase, glutamyl endopeptidase. In addition proteases may show a preference for a certain group of amino acids that share a certain resemblance. Such a group of preferred amino acids may comprise the hydrophobic amino acids, only the bulky hydrophobic amino acids, small hydrophobic, or just small amino acids, large positively charged amino acids, etc, etc. Apart from preferences for P1 and P1' residues also particular preferences or exclusions may exist for residues preferred by other subsites on the protease. Such multiple preferences can result in proteases that are very specific for only those sequences that satisfy multiple binding requirements at the same time. In general it should be realized that protease are rather promiscuous enzymes. Even very specific protease may cleave peptides that do not comply with the generally observed preference of the protease. In addition it should be realized that environmental conditions such as pH, temperature, ionic strength, water activity, presence of solvents, presence of competing substrates or inhibitors may influence the preferences of the proteases. Environmental condition may not only influence the protease but also influence the way the proteinacious substrate is presented to the protease.

14 00 CClassification by catalytic mechanism.

SProteases can be subdivided on the basis of their catalytic mechanism. It should be understood that for each catalytic mechanism the above classification based on specificity leads to further subdivision for each type of mechanism. Four major classes of proteases are known and are designated by the principal functional group in the active site: the serine proteases (EC 3.4.21 endo peptidase, EC 3.4.16 carboxy 0 peptidase), the thiol or cysteine proteases (EC 3.4.22 endo peptidase, EC 3.4.18 00 10 carboxy peptidase), the carboxyl or aspartic proteases (EC 3.4.23 endo peptidase) and O metallo proteases (EC 3.4.24 endo peptidase, EC 3.4.18 carboxy peptidase). There are characteristic inhibitors of the members of each catalytic type of protease. These small inhibitors irreversibly modify an amino acid residue of the protease active site.

For example, the serine protease are inactivated by Phenyl Methane Sulfonyl Fluoride (PMSF) and Diisopropyl Fluoro Phosphate (DFP), which react with the active Serine whereas the chloromethylketone derivatives react with the Histidine of the catalytic triad. Phosphoramidon and 1,10 Phenanthroflne typically inhibit metallo proteases.

Inhibition by Pepstatin generally indicates an aspartic protease. E64 inhibits thiol protease specifically. Amastatin and Bestatin inhibit various aminopeptidases.

Substantial variations in susceptibility of the proteases to the inhibitors are observed, even within one catalytic class. To a certain extent this might be related to the specificity of the protease. In case binding site architecture prevents a mechanism based inhibitor to approach the catalytic site, then such a protease escapes from inhibition and identification of the type of mechanism based on inhibition is prohibited.

Chymostation for example is a potent inhibitor for serine protease with chymotrypsin like specificity, Elastatinal inhibits elastase like serine proteases and does not react with trypsin or chymostrypsin, 4 amido PMSF (APMSF) inhibits only serine proteases with trypsin like specificity. Extensive accounts of the use of inhibitors in the classification of proteases include Barret and Salvesen, Proteinase Inhibitors, Elsevier Amstardam, 1986; Bond and Beynon (eds), Proteolytic Enzymes, A Practical Approach, IRL Press, Oxford, 1989; Methods in Enzymology, eds E.J.Barret, volume 244, 1994 and volume 248, 1995; E.Shaw, Cysteinyl proteinases and their selective inactivation, Adv Enzymol. 63:271-347 (1990) Classification according to optimal performance conditions.

VV ULIUOU1LJ r L I/Ir'ULIuiYr 4 00 The catalytic mechanism of a proteases and the requirement for its conformational Sintegrity determine mainly the conditions under which the protease can be utilized.

SFinding the protease that performs optimal under application conditions is a major challenge. Often conditions at which proteases have to perform are not optimal and do represent a compromise between the ideal conditions for a particular application and the conditions which would suit the protease best. Apart from the particular properties of the protease it should be realized that also the presentation of a proteinacious Ssubstrates is dependant on the conditions, and as such determines also which 0 conditions are most effective for proteolysis. Specifications for the enzyme that are 00 10 relevant for application comprise for example the pH dependence, the temperature Sdependence, sensitivity for or the dependence of metal ions, ionic strength, salt concentration, solvent compatibility. Another factor of major importance is the specific activity of a protease. The higher the enzyme's specific activity, the less enzyme is needed for a specific conversion. Lower enzyme requirements imply lower costs and lower protein contamination levels.

The pH is a major parameter that determines protease performance in an application.

Therefor pH dependence is an important parameter to group proteases. The major groups that are recognized are the acid proteases, the neutral proteases, the alkaline proteases and the high alkaline proteases. The optimum pH matches only to some extent the proteolytic mechanism, eg aspartic protease show often an optimum at acidic pH, metalloproteases and thiol proteases often perform optimal around neutral pH to slightly alkaline, serine peptidases are mainly active in the alkaiine and high alkaline region. For each class exceptions are known. In addition the overall water activity of the system plays a role. The pH optimum of a protease is defined as the pH range where the protease exhibits an optimal hydrolysis rate for the majority of its substrates in a particular environment under particular conditions. This range can be narrow, e.g. one pH unit, as well as quite broad, 3-4 pH units. In general the pH optimum is also dependant on the nature of the proteinacious substrate. Both the turnover rate as well as the specificity may vary as a function of pH. For a certain efficacy it can be desirable to use the protease far from its pH optimum because production of less desired peptides is avoided. Less desired peptides might be for example very short peptides or peptides causing a bitter taste. In addition a more narrow specificity can be a reason to choose conditions that deviate from optimal conditions with respect to turnover rate. Dependant on the pH the specificity may be narrow, e.g. only cleaving the peptide chain in one particular position or before or after one particular amino acid, or broader, e.g. cleaving a chain at multiple positions or 9 t ULflJUVttL 1 UIII~ V-~VIIU- 16 00 cleaving before or after more different types of amino acids. In fact the pH dependence N, might be an important tool to regulate the proteolytic activity in an application. In case Fthe pH shifts during the process the proteolysis might cease spontaneously without the Sneed for further treatment to inactivate the protease. In some cases the proteolysis itself may be the driver of the pH shift.

Very crucial for application of proteases is their handling and operating stability. As protease stability is strongly affected by the working temperature, stability is often also Sreferred to as thermostability. In general the stability of a protease indicates how long a 00 10 protease retains its proteolytic activity under particular conditions. Particular conditions Smay comprise fermentation conditions, conditions during isolation and down stream processing of the enzyme, storage conditions, formulation and operating or application conditions. In case particular conditions encompass elevated temperatures stability in general refers to thermostability. Apart from the general causes for enzyme inactivation such as chemical modification, unfolding, aggregation etc, main problem with proteases is that they are easy subject to autodegradation. Especially for the utilization of proteases the temperature optimum is a relevant criterion to group proteases.

Although there are different definitions, economically the most useful definition is the temperature or the temperature range in which the protease is most productive in a certain application. Protease productivity is a function of both the stability and the turnover rate. Where elevated temperature in general will increase the turnover rate, rapid inactivation will counteract the increase in turnover rate and ultimately lead to low productivity. The conformational stability of the protease under a given process condition will determine its maximum operating temperature. The temperature at which the protease looses it active conformation, often indicated as unfolding or melting point, can be determined according various methods, for example NMR, Circular Dichroism Spectroscopy, Differential Scanning Calorimetry etc etc. For protease unfolding is usually accompanied by a tremendous increase in autodegradation rate.

In applications where low temperatures are required protease may be selected with emphasis on a high intrinsic activity at low to moderate temperature. As under such conditions inactivation is relatively slow, under these conditions activity might largely determine productivity. In processes where only during a short period protease activity is required, the stability of the protease might be used as a switch to turn the protease off. In such case more labile instead of very thermostable protease might be preferred.

I I -1 1L ~L(YIUIIV)~V- 17 00 O Other environmental parameters which may play a role in selecting the appropriate Sprotease may be its sensitivity to salts. The compatibility with metal ions which are ;found frequently at low concentrations in various natural materials can be crucial for Scertain applications. In particular with metallo proteases certain ions may replace the catalytic metal ion and reduce or even abolish activity completely. In some applications metal ions have to be added on purpose in order to prevent the washout of the metal Sions coordinated to the protease. It is well known that for the sake of enzyme stability Sand life-time, calcium ions have to be supplied in order to prevent dissociation of Sprotein bound calcium.

00 SMost microorganisms show a certain tolerance with respect to adapting to changes in the environmental condition. As a consequence at least the proteolytic spectrum that the organism is able to produce are likely to show at least similar tolerances. Such a proteolyitic spectrum might be covered by many proteases covering together the hole spectrum or by only a few proteases of a broad spectrum. Taking into account the whole proteolytic spectrum of a microorganism it can be very important to take the location into account.

Cellular localisation and characterization of proteolytic processing and degradation From an industrial point of view the proteases which are excreted from the cell have specific advantages with respect to producibility at a large scale and stress tolerance as they have to survive without protection of the cell. The large group of cellular protease can be further subdivided in soluble and membrane bound. Membrane bound may comprise protease at the inside as well the outside of the membrane. Intracellular soluble protease may be subdivided further according to specific compartments of the cell where they do occur. As the cell shields the proteases to some extent from the environment and because the cell controls the conditions in the cell, intracellular protease might be more sensitive to large environmental changes and their optima might correlate better with the specific intacellualr conditions. Knowing the conditions of the cellular department where the protease resides might indicate their preferences.

Where extracellular protease in general do not require any regulation any more once excreted from the cell, intracellular proteases are often subject to more complicated control and regulation.

With respect to the function of a particular protease, its localisation is often very V V J VLV VVVX A V^ JL J A-Jjk V *JJ "U A 18 00 O important; for example, a lot of the vacuolar and periplasmic proteases are involved in C protein degradation, while many of the membrane-bound proteases are important in Sprotein processing (Suarez Rendueles and Wolf, 1988).

A comprehensive review on the biological properties and evolution of proteases has been published in van den Hombergh: Thesis Landbouwuniversiteit Wageningen: An i' analysis of the proteolytic system in Aspergillus in order to improve protein production C(N ISBN 90-5485-545-2, which is hereby incorporated by reference herein.

00 10 The protease problem An important reason for the interest in microbial proteases are protease related expression problems observed in several expression hosts used in bioprocess industry.

The increasing use of heterologous hosts for the production of proteins, by recombinant DNA technology, has recently brought this problem into focus, since it seems that heterologous proteins are more prone to proteolysis (Archer et al., 1992; van den Hombergh et al., 1996b).

In S. cerevisiae, already in the early eighties the protease problem and the involvement of several proteases, thus complicating targetted gene disruption approaches to overcome this problem, was recognised. During secretion a protein is exposed to several proteolytic activities residing in the secretory pathway. Additionally, in a prototrophic microorganism as Aspergillus secreted proteins can be exposed to several extracellular proteolytic activities The problem of degradation of heterologously expressed proteins is well documented in Aspergillus (van den Hombergh Thesis Landbouwuniversiteit Wageningen: An analysis of the proteolytic system in Aspergillus in order to improve protein production ISBN 90-5485-545-2) and has been reported in the expression of cow prochymosin, human interferon t-2 tPA, GMCSF, IL6, lactoferrin, chicken egg-white lysosyme, porcine plA2, A. niger pectin lyase B, E. coli enterotoxin B and j-glucoronidase, and Erwinia carotovora pectate lyase 3.

The problem of proteolysis may be addressed at several stages in protein production.

Bioprocess engineers may address the problem of proteolysis by downstream V I% UA IUOUAJ PCT/EP02/01984 19 00 processing at low temperatures, by early separation of product and protease(s) or by use of protease inhibitors. These may all lead to successful reduction of the problem.

SHowever it is certainly not eliminated, because much of the degradation occurs in vivo Sduring the production of the protein.

In understanding how proteolysis is controlled in the cell, a major question concerns the recognition mechanism by which proteolysis is triggered. Into what extent are yC proteolytically susceptable (heterologous) proteins recognised as aberrant because of misfolding or, if correctly folded, as 'foreign', because they do not posses features

OO

0 10 essential for stability which are specific to the host. Various types of stress can cause the .q overall proteolysis in a cell to increase significantly. Factors known to increase rate of proteolysis include nutrient starvation and various other types of stress elevation of temperature, osmotic stress, toxic substances and expression of certain heterologous proteins). To deal with proteolysis-related expression problems in vivo, several approaches have been proven succesfull as will be discussed below. However, we have to keep in mind that true 'non-proteolytic cells' cannot exist, since proteolysis by intracellular proteases is involved in many essential metabolic and 'housekeeping' reactions. Reducing proteolysis will therefore always be a process in which the changed genetical background which results in decreased proteolytic has to be analysed for potential secundary effects which could lead to reduced protein production reduced growth rate or sporulation).

Disruption of proteases in filamentous fungal expression hosts Berka and coworkers (1990) describe the eloning and disruption of the A. awamori pepA gene. More recently, three disrupted aspartyl proteases in A. niger have been described.

Disruptants for both the major extracellular aspartyl proteases and the major vacuolar aspartyl protease were described. Double and triple disruptants were generated via recombination and tested for protease spectra and expiession and secretion of the A.

niger pectin lyase PELB protein, which is very susceptable to proteolytic degradation (van den Hombergh et al., 1995). Disruption of pepA and pepB resulted both in reduction of extracellular protease activities, 80% and 6 respectively. In the ApepE disruptant also other (vacuolar) protease activities were severely affected caused by inactivating of the proteolytic cascade for other vacuolar proteases. Reduced extracellular activities correlated with reduced in vitro degradation of PELB and improved in vivo expression of pe/B (van den Hombergh et al., 1996f).

00 0 Protease deficient (prt) mutants filamentous fungi SSeveral Aspergillus protease deficient mutants have been studied whether protein Sproduction is improved. Archer and coworkers describe the reduced proteolysis of Hen egg white lysozyme in supernatants of an A. niger double prt mutant generated by Mattern and coworkers (1992) and conclude that although the degradation is not absent, it is significantly reduced. Van den Hombergh et al. (1995) show that the in vitro Sdegradation of A. niger PELB is reduced in all seven prt complementation groups they Shave isolated. Virtually no degradation is observed in the prtB, prtF and prtG mutants.

SRecently, the expression of the peB gene was shown to be improved in six 0 0 10 complementation groups tested (prtA-F) and highest expression levels were observed in Sthe prtB, prtF and prtG mutants. In addition to the single mutants, which contained residual extracellular proteolytic activities varying from 2-80 compared to wild type activity, double mutants were generated both by recombination and by additional rounds of mutagenesis. Via this approach several double prt mutants were selected and further characterised, which showed a further reduction of PELB degradation compared to their parental strains.

Instead of elimination of protease activities via disruption or mutagenesis, reduced proteolysis can also be achieved via down-regulation of the interfering proteolytic activities. This may be achieved by genetically altering the promoter or other regulatory sequences of the gene. As shown by Fraissinet-Tachet and coworkers (1996) the extracellular proteases in A. niger are all regulated by carbon catabolite repression and nitrogen metabolite repression. Nutrient starvation also causes the overall proteolysis rate in a cell to increase stromgly, which makes sense for a cell that lacks nutrients but posses proteins, that under starvation conditions are not needed or needed only in smaller amounts. In expression strategies which allow high expression on media containing high glucose and ammonium concentrations reduced proteolysis has been reported. Several constitutive glycolytic promoters (gpd and pkiA) are highly expressed under these conditions and can also be used to drive (heterologous) gene expression in continuous fermentations. The type of nutrient starvation imposed can influence different proteases to varying extent, which means that the importance of nutrient conditions in a given process depend on the type of proteolysis that is involved. Specific proteolysis may therefore be induced by conditions of substrate limitation which are frequently used in many large-scale fermentation processes.

The protease problem can nowadays be addressed in part by one or more of the above l' V21 t u'uuolo o 2C1rU2IU 194 00 strategies. However, the residual proteolytic activity of yet unidentified proteolytic Senzymes still constitutes a major problem in the art. In order to further reduce the level of Sunwanted proteolysis, there is a great need in the art to identify novel proteases responsible for degradation of homologously and heterologously expressed proteins.

This invention provides such novel protease gene sequences encoding novel proteases.

Once the primary sequence of a novel protease gene is known, one or more of the Sabove recombinant DNA strategies may be employed to produce (knock-out) mutants C with reduced proteolytic activity.

00

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Despite the widespread applications of proteases in a great number of industrial processes, current enzymes also have significant shortcomings with respect to at least one of the following properties.

When added to animal feed, current proteases are not sufficiently resistant to digestive enzymes present in the gastrointestinal (GI) tract of e.g. pigs and poultry.

With respect to another aspect, the currently available enzymes are not sufficiently resistant to specific (high) temperatures and (high) pressure conditions that are applied during extrusion or pelleting operations.

Also, the current enzymes are not sufficiently active in a pH range of 3-7, conditions prevailing in many food, beverage products as well as in in the GI tract of most animals.

According to yet another aspect the specificity of the currently available proteases is very limited which results in the inability of the existing enzymes to degrade or to dissolve certain "protease resistant"proteins thus resulting in low peptide or amino acid yields. Moreover proteases with new specificities allow the synthesis of new peptides.

Yet another drawback of the currently available enzymes is their low specific activity.

It is therefore clear that for a large number of applications a strong desire exists for proteases that are more resistant to digestive enzymes, high temperature and/or pressure and which exhibit novel specificities regarding their sites of hydrolysis. The present invention provides such enzymes.

22 00 Aspects of the invention SAn aspect of the invention is to provide novel polynucleotides encoding novel proteases. A further aspect is to provide naturally and recombinantly produced roteases as well as recombinant strains producing these. Such strains may also be used to produce classical fermentation products faster or with higher yields. Yet another aspect of the invention is to provide a filamentous fungus strain defective in Sproducing a protease according to the invention. Such strains may be used for a more Sefficient production of heterologous or homologous proteins. Also antibodies and fusion polypeptides are part of the invention as well as methods of making and using the polynucleotides and polypeptides according to the invention.

Throughout the description and claims of this specification, use of the word "comprise" and variations of the word, such as "comprising" and "comprises", is not intended to exclude other additives, components, integers or steps.

A reference herein to a patent document or other matter which is given as prior art is not to be taken as an admission that that document or matter was, in Australia, known or that the information it contains was part of the common general knowledge as at the priority date of any of the claims.

Summary of the invention The invention provides for novel polynucleotides encoding novel proteases.

More in particular, the invention provides for polynucleotides having a nucleotide sequence that hybridises (preferably under highly stringent conditions) to a sequence according to a sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 57 or to a sequence selected from the group consisting of SEQ ID NO: 58 to SEQ ID NO: 114. Consequently, the invention provides nucleic acids that are about preferably 65%, more preferably 70%, even more preferably 75%, 80%, 95%, 96%, 97%, 98% or 99% homologous to the sequences according to a sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 57 or a sequence selected from the group consisting of SEQ ID NO: 58 to SEQ ID NO: 114.

In a more preferred embodiment the invention provides for such an isolated polynucleotide obtainable from a filamentous fungus, preferably Aspergilli, in particular W.*VdiuF1ES1A hosW7633 T7633 m o,.ded pt 22 16.0.lOS.dw 00 0 A. niger is preferred.

SIn one embodiment, the invention provides for an isolated polynucleotide comprising a Snucleic acid sequence encoding a polypeptide with an amino acid sequence selected S 5 from the group consisting of SEQ ID NO: 115 to SEQ ID NO: 171 or functional equivalents thereof.

itr In a further preferred embodiment, the invention provides an isolated polynucleotide 00 ;IXTILE\U ',rm67733 1%770131 .1 ,-dcd M 22 A b 0 09 d1w 00 O encoding at least one functional domain of a polypeptide according to a sequence C selected from the group consisting of SEQ ID NO: 115 to SEQ ID NO: 171 or functional equivalents thereof.

In a preferred embodiment the invention provides a protease gene according to a sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 57. In Sanother aspect the invention provides a polynucleotide, preferably a cDNA encoding an Ns A. niger protease selected from the group consisting of SEQ ID NO: 115 to SEQ ID N NO: 171 or variants or fragments of that polypeptide. In a preferred embodiment the cDNA has a sequence selected from the group consisting of SEQ ID NO: 58 to SEQ ID SNO: 114 or functional equivalents thereof.

A genomic clone encoding a polypeptide according to the invention may also be obtained by selecting suitable probes to specifically amplify a genomic region corresponding to any of the sequences according to SEQ ID NO: 1 to SEQ ID NO: 57 or fragments thereof, hybridising that probe under suitable conditions to genomic DNA obtained from a suitable organism, such as Aspergillus, e.g. A. niger, amplifying the desired fragment e.g. by PCR (polymerase chain reaction) followed by purifying and cloning of the amplified fragment.

In an even further preferred embodiment, the invention provides for a polynucleotide comprising the coding sequence of the genomic polynucleotides according to the invention, preferred is a polynucleotide sequence selected from the group consisting of SEQ ID NO: 58 to SEQ ID NO: 114.

In another preferred embodiment, the invention provides a cDNA obtainable by cloning and expressing a sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 57 into a suitable host organism, such as A. niger.

A polypeptide according to the invention may also be obtained by cloning and expressing a sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 57 into a suitable host organism, such as A. niger.

The invention also relates to vectors comprising a polynucleotide sequence according to the invention and primers, probes and fragments that may be used to amplify or detect the DNA according to the invention.

00

O

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rC In a further preferred embodiment, a vector is provided wherein the polynucleotide sequence according to the invention is functionally linked with regulatory sequences suitable for expression of the encoded amino acid sequence in a suitable host cell, such as A. niger or A. oryzea. The invention also provides methods for preparing polynucleotides and vectors according to the invention.

The invention also relates to recombinantly produced host cells that contain Sheterologous or homologous polynucleotides according to the invention.

00 0 In one embodiment, the invention provides recombinant host cells wherein the expression of a protease according to the invention is significantly reduced or wherein the activity of the protease is reduced or wherein the protease is even inactivated.

Such recombinants are especially useful for the expression of homologous or heterologous proteins.

In another embodiment, the invention provides recombinant host cells wherein the expression of a protease according to the invention is significantly increased or wherein the activity of the protease is increased. Such recombinants are especially useful for the expression of homologous or heterologous proteins where maturation is seriously hampered in case the required proteolytic cleavage becomes the rate limiting step.

In another embodiment the invention provides for a recombinantly produced host cell that contains heterologous or homologousDNA according to the invention, preferably DNA encoding proteins bearing signal sequnences and wherein the cell is capable of producing a functional protease according to the invention, preferably a cell capable of over-expressing the protease according to the invention, for example an Aspergillus strain comprising an increased copy number of a gene or cDNA according to the invention.

In another embodiment the invention provides for a recombinantly produced host cell that contains heterologous or homologous DNA according to the invention and wherein the cell is capable of secreting a functional protease according to the invention, preferably a cell capable of over-expressing and secreting the protease according to the invention, for example an Aspergillus strain comprising an increased copy number of a gene or cDNA according to the invention.

1 J UW /UVVOA.J 00 0 SIn yet another aspect of the invention, a purified polypeptide is provided. The Spolypeptides according to the invention include the polypeptides encoded by the polynucleotides according to the invention. Especially preferred is a polypeptide according to a sequence selected from the group consisting of SEQ ID NO: 115 to SEQ ID NO: 171 or functional equivalents thereof.

N The invention also provides for antibodies reactive with a polypeptide according to the C- invention. These antibodies may be polyclonal, yet especially preferred are monoclonal 00 0 10 antibodies. Such antibodies are particularly useful for purifying the polypeptides 0 according to the invention.

Fusion proteins comprising a polypeptide according to the invention are also within the scope of the invention. The invention also provides methods of making the polypeptides according to the invention.

The invention further relates to a method for diagnosing aspergillosis either by detecting the presence of a polypeptide according to the invention or functional equivalents thereof, or by detecting the presence of a DNA according to the invention or fragments or functional equivalents thereof.

The invention also relates to the use of the protease according to the invention in an industrial process as described herein Detailed description of the invention Polynucleotides The present invention provides polynucleotides encoding proteases having an amino acid sequence selected from the group consisting of SEQ ID NO: 115 to SEQ ID NO: 171 or functional equivalents thereof. The sequence of these genes was determined by sequencing a genomic clone obtained from Aspergillus niger. The invention provides polynucleotide sequences comprising the gene encoding these proteases as well as their complete cDNA sequence and its coding sequence. Accordingly, the invention 26 00 relates to an isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 57 or a sequence selected from Sthe group consisting of SEQ ID NO: 58 to SEQ ID NO: 114 or functional equivalents thereof.

More in particular, the invention relates to an isolated polynucleotide hybridisable under stringent conditions to a polynucleotide selected from the group consisting of SEQ ID CN NO: 1 to SEQ ID NO: 57 or a sequence selected from the group consisting of SEQ ID CN NO: 58 to SEQ ID NO: 114 preferably under highly stringent conditions.

00 Advantageously, such polynucleotides may be obtained from filamentous fungi, in 0C particular from Aspergillus niger. More specifically, the invention relates to an isolated polynucleotide having a nucleotide sequence according to a sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 57 or a sequence selected from the group consisting of SEQ ID NO: 58 to SEQ ID NO: 114.

The invention also relates to an isolated polynucleotide encoding at least one functional domain of a polypeptide according to a sequence selected from the group consisting of SEQ ID NO: 115 to SEQ ID NO: 171 or functional equivalents thereof.

As used herein, the terms "gene" and "recombinant gene" refer to nucleic acid molecules which may be isolated from chromosomal DNA, which include an open reading frame encoding a protein, e.g. an A. niger protease. A gene may include coding sequences, non-coding sequences, introns and regulatory sequences.

Moreover, a gene refers to an isolated nueleic acid molecule as defined herein.

A nucleic acid molecule of the present invention, such as a nucleic acid molecule having the nucleotide sequence of a sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 57 or a sequence selected from the group consisting of SEQ ID NO: 58 to SEQ ID NO: 114 or a functional equivalent thereof, can be isolated using standard molecular biology techniques and the sequence information provided herein. For example, using all or portion of the nucleic acid sequence of a sequence selected from the group consisting of SEQ !D NO: 1 to SEQ !D NO: 57 or the nucleotide sequence of a sequence selected from the group consisting of SEQ ID NO: 58 to SEQ ID NO: 114 as a hybridization probe, nucleic acid molecules according to the invention can be isolated using standard hybridization and cloning techniques (e.

as described in Sambrook, Fritsh, E. and Maniatis, T. Molecular Cloning: A 1. -v 00 O Laboratory Manual.2nd, ed., Cold Spring Harbor Laboratory, Cold Spring Harbor t C Laboratory Press, Cold Spring Harbor, NY, 1989).

Moreover, a nucleic acid molecule encompassing all or a portion of a sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 57 or a sequence selected from the group consisting of SEQ ID NO: 58 to SEQ ID NO: 114 can be isolated by the polymerase chain reaction (PCR) using synthetic oligonucleotide Cprimers designed based upon the sequence information contained in a sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 57 or a sequence 00 10 selected from the group consisting of SEQ ID NO: 58 to SEQ ID NO: 114.

A nucleic acid of the invention can be amplified using cDNA, mRNA 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, oligonucleolides corresponding to or hybridisable to nucleotide sequences according to the invention can be prepared by standard synthetic techniques, e. using an automated DNA synthesizer.

In a preferred embodiment, an isolated nucleic acid molecule of the invention comprises the nucleotide sequence shown in a sequence selected from the group consisting of SEQ ID NO: 58 to SEQ ID NO: 114. The sequence of a sequence selected from the group consisting of SE( ID NO: 58 to SEQ ID NO: 114 corresponds to the coding region of the A. niger protease cDNA. This cDNA comprises sequences encoding the A. niger protease polypeptide according to a sequence selected from the group consisting of SEQ ID NO: 115 to SEQ ID NO: 171.

In another preferred embodiment, an isolated nucleic acid molecule of the invention comprises a nucleic acid molecule which is a complement of the nucleotide sequence shown in a sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 57 or a sequence selected from the group consisting of SEQ ID NO: 58 to SEQ !D NO: 114 or a functional equivalent of these nucleotide sequences.

A nucleic acid molecule which is complementary to another nucleotide sequence is one which is sufficiently complementary to the other nucleotide sequence such that it can V, s.I UVOV-- -1 -1 28 00 hybridize to the other nucleotide sequence thereby forming a stable duplex.

SOne aspect of the invention pertains to isolated nucleic acid molecules that encode a polypeptide of the invention or a functional equivalent thereof such as a biologically active fragment or domain, as well as nucleic acid molecules sufficient for use as hybridisation probes to identify nucleic acid molecules encoding a polypeptide of the Sinvention and fragments of such nucleic acid molecules suitable for use as PCR NC primers for the amplification or mutation of nucleic acid molecules.

C 10 An "isolated polynucleotide" or "isolated nucleic acid" is a DNA or RNA that is not 3 immediately contiguous with both of the coding sequences with which it is immediately contiguous (one on the 5' end and one on the 3' end) in the naturally occurring genome of the organism from which it is derived. Thus, in one embodiment, an isolated nucleic acid includes some or all of the 5' non-coding promotor) sequences that are immediately contiguous to the coding sequence. The term therefore includes, for example, a recombinant DNA that is incorporated into a vector, into an autonomously replicating plasmid or virus, or into the genomic DNA of a prokaryote or eukaryote, or which exists as a separate molecule a cDNA or a genomic DNA fragment produced by PCR or restriction endonuclease treatment) independent of other sequences. It also includes a recombinant DNA that is part of a hybrid gene encoding an additional polypeptide that is substantially free of cellular material, viral material, or culture medium (when produced by recombinant DNA techniques), or chemical precursors or other chemicals (when chemically synthesized). Moreover, an "isolated nucleic acid fragment" is a nucleic acid fragment that is not naturally occurring as a fragment and would not be found in the natural state.

As used herein, the terms "polynucleotide" or "nucleic acid molecule" are intended to include DNA molecules cDNA or genomic DNA) and RNA molecules mRNA) and analogs of the DNA or RNA generated using nucleotide analogs. The nucleic acid molecule can be single-stranded or double-stranded, but preferably is double-stranded DNA. The nucleic acid may be synthesized using oligonucleotide analogs or derivatives inosine or phosphorothioate nucleotides). Such oligonucleotides can be used, for example, to prepare nucleic acids that have altered base-pairing abilities or increased resistance to nucleases.

Another embodiment of the invention provides an isolated nucleic acid molecule which 29 00 is antisense to a protease nucleic acid molecule, the coding strand of a protease nucleic acid molecule. Also included within the scope of the invention are the ;Zcomplement strands of the nucleic acid molecules described herein.

Sequencing errors n The sequence information as provided herein should not be so narrowly construed as to require inclusion of erroneously identified bases. The specific sequences disclosed herein can be readily used to isolate the complete gene from filamentous fungi, in 00 10 particular A. niger which in turn can easily be subjected to further sequence analyses thereby identifying sequencing errors.

Unless otherwise indicated, all nucleotide sequences determined by sequencing a DNA molecule herein were determined using an automated DNA sequencer and all amino acid sequences of polypeptides encoded by DNA molecules determined herein were predicted by translation of a DNA sequence determined as above. Therefore, as is known in the art for any DNA sequence determined by this automated approach, any nucleotide sequence determined herein may contain some errors. Nucleotide sequences determined by automation are typically at least about 90% identical, more typically at least about 95% to at least about 99.9% identical to the actual nucleotide sequence of the sequenced DNA molecule. The actual sequence can be more precisely determined by other approaches including manual DNA sequencing methods well known in the art. As is also known in the art, a single insertion or deletion in a determined nucleotide sequence compared to the actual sequence will cause a frame shift in translation of the nucleotide sequence such that the predicted amino acid sequence encoded by a determined nucleotide sequence will be completely different from the amino acid sequence actually encoded by the sequenced DNA molecule, beginning at the point of such an insertion or deletion.

The person skilled in the art is capable of identifying such erroneously identified bases and knows how to correct for such errors.

Nucleic acid fragments, probes and primers A nucleic acid molecule according to the invention may comprise only a portion or a fragment of the nucleic acid sequence shown in a sequence selected from the group 00 O consisting of SEQ ID NO: 1 to SEQ ID NO: 57 or a sequence selected from the group Sconsisting of SEQ ID NO: 58 to SEQ ID NO: 114, for example a fragment which can be ;used as a probe or primer or a fragment encoding a portion of a protease protein. The Snucleotide sequence determined fron the cloning of the protease gene and cDNA allows for the generation of probes and primers designed for use in identifying and/or.

cloning other protease family members, as well as protease homologues from other Sspecies. The probe/primer typically comprises substantially purified oligonucleotide which typically comprises a region of nucleotide sequence that hybridizes preferably under highly stringent conditions to at least about 12 or 15, preferably about 18 or

O

10 preferably about 22 or 25, more preferably about 30, 35, 40, 45, 50, 55, 60, 65, or 75 or Smore consecutive nucleotides of a nucleotide sequence shown in a sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 57 or a sequence selected from the group consisting of SEQ ID NO: 58 to SEQ ID NO: 114 or of a functional equivalent thereof.

Probes based on the protease nucleotide sequences can be used to detect transcripts or genomic protease sequences encoding the-same or homologous proteins for instance in other organisms. In preferred embodiments, the probe further comprises a label group attached thereto, the label group can be a radioisotope, a fluorescent compound, an enzyme, or an enzyme cofactor. Such probes can also be used as part of a diagnostic test kit for identifying cells which express a protease protein.

Identity homology The terms "homology" or "percent identity" are used interchangeably herein. For the purpose of this invention, it is defined here that in order to determine the percent identity of two amino acid sequences or of two nucleic acid sequences, the sequences are aligned for optimal comparison purposes gaps can be introduced in the sequence of a first amino acid or nucleic acid sequence for optimal alignment with a second amino or nucleic acid sequence). The amino acid residues or nucleotides at corresponding amino acid positions or nucleotide positions are then compared. When a position in the first sequence is occupied by the same amino acid residue or nucleotide as the corresponding position in the second sequence, then the molecules are identical at that position. The percent identity between the two sequences is a function of the number of identical positions shared by the sequences identity number of identical positions/total number of positions overlapping positions) x 100).

31 00 Preferably, the two sequences are the same length.

SThe skilled person will be aware of the fact that several different computer programs are available to determine the homology between two sequences. For instance, a comparison of sequences and determination of percent identity between two sequences can be accomplished using a mathematical algorithm. In a preferred V embodiment, the percent identity between two amino acid sequences is determined C using the Needleman and Wunsch Mol. Biol. (48):444-453 (1970)) algorithm which C has been incorporated into the GAP program in the GCG software package (available at http://www.qcq.com), using either a Blossom 62 matrix or a PAM250 matrix, and a gap weight of 16,14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5, or 6. The skilled person will appreciate that all these different parameters will yield slightly different results but that the overall percentage identity of two sequences is not significantly altered when using different algorithms.

In yet another embodiment, the percent identity between two nucleotide sequences is determined using the GAP program in the GCG software package (available at http://www.qcq.com), using a NWSgapdna.CMP matrix and a gap weight of 40, 50, or 80 and a length weight of 1, 2, 3, 4, 5, or 6. In another embodiment, the percent identity two amino acid or nucleotide sequence is determined using the algorithm of E.

Meyers and W. Miller (CABIOS, 4:11-17 (1989) which has been incorporated into the ALIGN program (version 2.0) (available at http://veqa/iqh.cnrs.fr/bin/aliqn-quess.cqi), using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4.

The nucleic acid and protein sequences of the present invention can further be used as a "query sequence" to perform a search against public databases to, for example, identify other family members or related sequences. Such searches can be performed using the NBLAST and XBLAST programs (version 2.6) of Altschul, et al. (1990) J. Mol.

Biol. 215:403-10. BLAST nucleotide searches can be performed with the NBLAST program, score 100, wordlength 12 to obtain nucleotide sequences homologous to protease 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 protease 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, the default parameters of the 00 0 respective programs XBLAST and NBLAST) can be used. See C-i http://www.ncbi.nlm.nih.qov.

Hybridisation As used herein, the term "hybridizing" is intended to describe conditions for Ihybridization and washing under which nucleotide sequences at least about 50%, at least about 60%, at least about 70%, more preferably at least about 80%, even more preferably at least about 85% to 90%, more preferably at least 95% homologous to 00 10 each other typically remain hybridized to each other.

A preferred, non-limiting example of such hybridization conditions are hybridization in 6X sodium chloride/sodium citrate (SSC) at about 45 followed by one or more washes in 1 X SSC, 0.1 SDS at 50 preferably at 55 OC, preferably at 60 °C and even more preferably at 65 OC.

Highly stringent conditions include, for example, hybridizing at 68 OC in 5x Denhardt's solution/l.0% SDS and washing in 0.2x SSC/0.1% SDS at room temperature. Alternatively washing may be performed at 42 °C.

The skilled artisan will know which conditions to apply for stringent and highly stringent hybridisation conditions. Additional guidance regarding such conditions is readily available in the art, for example, in Sambrook et al., 1989, Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Press, and Ausubel et al. 1995, Current Protocols in Molecular Biology, (John Wiley Sons, Of course, a polynucleotide which hybridizes only to a poly A sequence (such as the 3' terminal poly(A) tract of mRNAs), or to a complementary stretch of T (or U) resides, would not be included in a polynucleotide of the invention used to specifically hybridize to a portion of a nucleic acid of the invention, since such a polynucleotide would hybridize to any nucleic acid molecule contain a poly stretch or the complement thereof practically any double-standed cDNA clone).

Obtaining full length DNA from other organisms In a typical approach, cDNA libraries constructed from other organisms, e.g.

00 O filamentous fungi, in particular from the species Aspergillus can be screened.

For example, Aspergillus strains can be screened for homologous protease polynucleotides by Northern blot analysis. Upon detection of transcripts homologous to polynucleotides according to the invention, cDNA libraries can be constructed from RNA isolated from the appropriate strain, utilizing standard techniques well known to Sthose of skill in the art. Alternatively, a total genomic DNA library can be screened Susing a probe hybridisable to a protease polynucleotide according to the invention.

00 Homologous gene sequences can be isolated, for example, by performing PCR using Stwo oligonucleotide primers or two degenerate oligonucleotide primer pools designed on the basis of nucleotide sequences as taught herein.

The template for the reaction can be cDNA obtained by reverse transcription of mRNA prepared from strains known or suspected to express a polynucleotide according to the invention. The PCR product can be subcloned and sequenced to ensure that the amplified sequences represent the sequences-of a new protease nucleic acid sequence, or a functional equivalent thereof.

The PCR fragment can then be used to isolate a full length cDNA clone by a variety of known methods. For example, the amplified fragment can be labeled and used to screen a bacteriophage or cosmid cDNA library. Alternatively, the labeled fragment can be used to screen a genomic library.

PCR technology also can be used to isolate full length cDNA sequences from other organisms. For example, RNA can be isolated, following standard procedures, from an appropriate cellular or tissue source. A reverse transcription reaction can be performed on the RNA using an oligonucleotide primer specific for the most 5' end of the amplified fragment for the priming of first strand synthesis.

The resulting RNA/DNA hybrid can then be "tailed" with guanines) using a standard terminal transferase reaction, the hybrid can be digested with RNase H, and second strand synthesis can then be primed with a poly-C primer). Thus, cDNA sequences upstream of the amplified fragment can easily be isolated. For a review of useful cloning strategies, see e.g.,Sambrook et al., supra; and Ausubel et al., supra.

00 Vectors Another aspect of the invention pertains to vectors, preferably expression vectors, containing a nucleic acid encoding a protease protein or a functional equivalent 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 t' 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 00 10 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 of plasmids. The terms "plasmid" and "vector" can be used interchangeably herein as the plasmid is the most commonly used form of vector. However, the invention is intended to include such other forms of expression vectors, su'ch as viral vectors replication defective retroviruses, adenoviruses and adeno-associated 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 vector includes 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, "operatively 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 signal). Such regulatory sequences are described, for example, in Goeddel; Gene Expression Technology: Methods in Enzymology 185, Academic Press, San Diego, CA (1990). Regulatory sequences include those which direct constitutive expression of a nucleotide sequence in many 00 0 types of host cells and those which direct expression of the nucleotide sequence only 0 CN in a certain host cell tissue-specific regulatory sequences). It will be appreciated §by those skilled in the art that the design of the expression vector can depend on such Sfactors 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, encoded by nucleic acids as described herein protease proteins, mutant forms of protease proteins, fragments, variants or functional equivalents thereof, fusion proteins, etc.).

00 10 The recombinant expression vectors of the invention can be designed for expression of O protease proteins in prokaryotic or eukaryotic cells. For example, protease proteins can be expressed in bacterial cells such as E. coli, insect cells (using baculovirus expression vectors) yeast cells 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.

Expression vectors useful in the present invention include chromosomal-, episomaland virus-derived vectors vectors derived from bacterial plasmids, bacteriophage, yeast episome, yeast chromosomal elements, viruses such as baculoviruses, papova viruses, vaccinia viruses, adenoviruses, fowl pox viruses, pseudorabies viruses and retroviruses, and vectors derived from combinations thereof, such as those derived from plasmid and bacteriophage genetic elements, such as cosmids and phagemids.

The DNA insert should be operatively linked to an appropriate promoter, such as the phage lambda PL promoter, the E. coli lac, trp and tac promoters, the SV40 early and late promoters and promoters of retroviral LTRs, to name a few. Other suitable promoters will be known to the skilled person. In a specific embodiment, promoters are preferred that are capable of directing a high expression level of proteases in filamentous fungi. Such promoters are known in the art. The expression constructs may contain sites for transcription initiation, termination, and, in the transcribed region, a ribosome binding site for translation. The coding portion of the mature transcripts expressed by the constructs will include a translation initiating AUG at the beginning and a termination codon appropriately positioned at the end of the polypeptide to be translated.

00

O

CN Vector DNA can be introduced into prokaryotic or eukaryotic cells via conventional Stransformation 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 DNA) into a host cell, including calcium phosphate or calcium chloride co-percipitation, DEAE-dextran-mediated transfection, transduction, infection, lipofection, cationic lipidmediated transfection or n electroporation. Suitable methods for transforming or transfecting host cells can be O found in Sambrook, et al. (Molecular Cloning: A Laboratory Manual, 2",ed. Cold Spring 00 10 Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, S1989), Davis et al., Basic Methods in Molecular Biology (1986) 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 methatrexate. Nucleic acid encoding a selectable marker can be introduced into a host cell on the same vector as that encoding a protease 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).

Expression of proteins in prokaryotes is often carried out in E. coli 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, e.g. 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 recognation sequences, include Factor Xa, 00 O thrombin and enterokinase.

SAs indicated, the expression vectors will preferably contain selectable markers. Such Smarkers include dihydrofolate reductase or neomycin resistance for eukarotic cell culture and tetracyline or ampicilling resistance for culturing in E. coli and other bacteria. Representative examples of appropriate host include bacterial cells, such as E. coli, Streptomyces and Salmonella typhimurium; fungal cells, such as yeast; insect n cells such as Drosophila S2 and Spodoptera Sf9; animal cells such as CHO, COS and 0 Bowes melanoma; and plant cells. Appropriate culture mediums and conditions for the 00 10 above-described host cells are known in the art.

Among vectors preferred for use in bacteria are pQE70, pQE60 and PQE-9, available from Qiagen; pBS vectors, Phagescript vectors, Bluescript vectors, pNH8A, pNH16A, pNH18A, pNH46A, available from Stratagene; and ptrc99a, pKK223-3, pKK233-3, pDR540, pRIT5 available from Pharmacia. Among preferred eukaryotic vectors are PWLNEO, pSV2CAT, pOG44, pZT1 and pSG available from Stratagene; and pSVK3, pBPV, pMSG and pSVL available from Pharmacia. Other suitable vectors will be readily apparent to the skilled artisan.

Among known bacterial promotors for use in the present invention include E. coli lad and lacZ promoters, the T3 and T7 promoters, the gpt promoter, the lambda PR, PL promoters and the trp promoter, the HSV thymidine kinase promoter, the early and late promoters, the promoters of retroviral LTRs, such as those of the Rous sarcoma virus and metallothionein promoters, such as the mouse metallothionein-l promoter.

Transcription of the DNA encoding the polypeptides of the present invention by higher eukaryotes may be increased by inserting an enhancer sequence into the vector.

Enhancers are cis-acting elements of DNA, usually about from 10 to 300 bp that act to increase transcriptional activity of a promoter in a given host cell-type. Examples of enhancers include the SV40 enhancer, which is located on the late side of the replication origin at bp 100 to 270, the cytomegalovirus early promoter enhancer, the polyoma enhancer on the late side of the replication origin, and adenovirus enhancers.

For secretion of the translated protein into the lumen of the endoplasmic reticulum, into the periplasmic space or into the extracellular environment, appropriate secretation 0( signal may be incorporated into the expressed polypeptide. The signals may be endogenous to the polypeptide or they may be heterologous signals.

SThe polypeptide may be expressed in a modified form, such as a fusion protein, and may include not only secretion signals but also additional heterologous functional regions. Thus, for instance, a region of additional amino acids, particularly charged amino acids, may be added to the N-terminus of the polypeptide to improve stability Sand persistence in the host cell, during purification or during subsequent handling and Sstorage. Also, peptide moieties may be added to the polypeptide to facilitate 00 10 purification.

Polypeptides according to the invention The invention provides an isolated polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 115 to SEQ ID NO: 171, an amino acid sequence obtainable by expressing a polynucleotide according to the invention or in a preferred embodiment of a sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 57 in an appropriate host, as well as an amino acid sequence obtainable by expressing a polynucleotide sequences selected from the group consisting of SEQ ID NO: 58 to SEQ ID NO: 114 in an appropriate host. Also, a peptide or polypeptide comprising a functional equivalent of the above polypeptides is comprised within the present invention. The above polypeptides.are collectively comprised in the term "polypeptides according to the invention" The terms "peptide" and "oligopeptide" are considered synonymous (as is commonly recognized) and each term can be used interchangeably as the context requires to indicate a chain of at least two amino acids coupled by peptidyl linkages. The word "polypeptide" is used herein for chains containing more than seven amino acid residues. All oligopeptide and polypeptide formulas or sequences herein are written from left to right and in the direction from amino terminus to carboxy terminus. The oneletter code of amino acids used herein is commonly known in the art and can be found in Sambrook, et al. (Molecular Cloning: A Laboratory Manual, 2 n d,ed. Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1989) By "isolated" polypeptide or protein is intended a polypeptide or protein removed from 00 O its native environment. For example, recombinantly produced polypeptides and N proteins expressed in host cells are considered isolated for purpose of the invention as Sare native or recombinant polypeptides which have been substantially purified by any Ssuitable technique such as, for example, the single-step purification method disclosed in Smith and Johnson, Gene 67:31-40 (1988).

The protease according to the invention can be recovered and purified from n recombinant cell cultures by well-known methods including ammonium sulfate or 0 ethanol precipitation, acid extraction, anion or cation exchange chromatography, 00 10 phosphocellulose chromatography, hydrophobic interaction chromatography, affinity 0chromatography, hydroxylapatite chromatography and lectin chromatography. For analytical purposes most preferably, high performance liquid chromatography ("HPLC") is employed for purification.

Polypeptides of the present invention include naturally purified products, products of chemical synthetic procedures, and products produced by recombinant techniques from a prokaryotic or eukaryotic host, including, for example, bacterial, yeast, higher plant, insect and mammalian cells. Depending upon the host employed in a recombinant production procedure, the polypeptides of the present invention may be glycosylated or may be non-glycosylated. In addition, polypeptides of the invention may also include an initial modified methionine residue, in some cases as a result of hostmediated processes.

Moreover, a protein according to the invention may be a precursor protein such as a zymogen, a hybrid protein, a protein obtained as a pro sequence or pre-pro sequence, or any other type of immature form.

Protein fragments The invention also features biologically active fragments of the polypeptides according to the invention.

Biologically active fragments of a polypeptide of the invention include polypeptides comprising amino acid sequences sufficiently identical to or derived from the amino acid sequence of the protease protein the amino acid sequence of a sequence selected from the group consisting of SEQ ID NO: 115 to SEQ ID NO: 171), which 00 0 include fewer amino acids than the full length protein, and exhibit at least one biological CN activity of the corresponding full-length protein. Typically, biologically active fragments Scomprise a domain or motif with at least one activity of the protease protein. A biologically active fragment of a protein of the invention can be a polypeptide which is, for example, 10, 25, 50, 100 or more amino acids in length. 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 biological activities of the n native form of a polypeptide of the invention.

00 10 The invention also features nucleic acid fragments which encode the above biologically Sactive fragments of the protease protein.

Fusion proteins The proteins of the present invention or functional equivalents thereof, biologically active portions thereof, can be operatively linked to a non-protease polypeptide heterologous amino acid sequences) to form fusion proteins. As used herein, a protease "chimeric protein" or "fusion protein" comprises a protease polypeptide operatively linked to a non-protease polypeptide. A "protease polypeptide" refers to a polypeptide having an amino acid sequence correspondirg to a polypeptide sequence according to the invention, whereas a "non-protease polypeptide" refers to a polypeptide having an amino acid sequence corresponding to a protein which is not substantially homologous to aprotein according to the invention, a protein which is different from the protease protein and which is derived from the same or a different organism. Within a protease fusion protein the protease polypeptide can correspond to all or a portion of a protein according to the invention. In a preferred embodiment, a protease fusion protein comprises at least one biologically active fragment of a protein according to the invention. In another preferred embodiment, a protease fusion protein comprises at least two biologically active portions of a protein according to the invention. Within the fusion protein, the term "operatively linked" is intended to indicate that the protease polypeptide and the non-protease polypeptide are fused in-frame to each other. The non-protease polypeptide can be fused to the N-terminus or Cterminus of the protease polypeptide.

For example, in one embodiment, the fusion protein is a GST-protease fusion protein in which the protease sequences are fused to the C-terminus of the GST sequences.

00 0 Such fusion proteins can facilitate the purification of recombinant protease. In another Sembodiment, the fusion protein is a protease protein containing a heterologous signal y sequence at its N-terminus. In certain host cells mammalian and Yeast host Scells), expression and/or secretion of protease can be increased through use of a hetereologous signal sequence.

In another example, the gp67 secretory sequence of the baculovirus envelope protein Scan be used as a heterologous signal sequence (Current Protocols in Molecular SBiology, Ausubel et al., eds., John Wiley Sons, 1992). Other examples of eukaryotic Sheterologous signal sequences include the secretory sequences of melittin and human 00 10 placental alkaline phosphatase (Stratagene; La Jolla, California). In yet another 0example, useful prokarytic heterologous signal sequences include the phoA secretory signal (Sambrook et al., supra) and the protein A secretory signal (Pharmacia Biotech; Piscataway, New Jersey).

A signal sequence can be used to facilitate secretion and isolation of a protein or polypeptide of the invention. Signal sequences are typically characterized by a core of hydrophobic amino acids which are generally-cleaved from the mature protein during secretion in one or more cleavage events. Such signal peptides contain processing sites that allow cleavage of the signal sequence from the mature proteins as they pass through the secretory pathway. The signal sequence directs secretion of the protein, such as from a eukaryotic host into which the expression vector is transformed, and the signal sequence is subsequently or concurrently cleaved. The protein can then be readily purified from the extracellular medium by art recognized methods. Alternatively, the signal sequence can be linked to the protein of interest using a sequence which facilitates purification, such as with a GST domain. Thus, for instance, the sequence encoding the polypeptide may be fused to a marker sequence, such as a sequence encoding a peptide, which facilitates purification of the fused polypeptide. In certain preferred embodiments of this aspect of the invention, the marker sequence is a hexahistidine peptide, such as the tag provided in a pQE vector (Qiagen, Inc.), among others, many of which are commercially available. As described in Gentz et al, Proc.

Natl. Acad. Sci. USA 86:821-824 (1989), for instance, hexa-histidine provides for convenient purificaton of the fusion protein. The HA tag is another peptide useful for purification which corresponds to an epitope derived of influenza hemaglutinin protein, which has been described by Wilson et al., Cell 37:767 (1984), for instance.

Preferably, a protease chimeric or fusion protein of the invention is produced by 0 standard recombinant DNA techniques. For example, DNA fragments coding for the Sdifferent polypeptide sequences are ligated together in-frame in accordance with Sconventional 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.

SAlternatively, PCR amplification of gene fragments can be carried out using anchor Sprimers which give rise to complementary overhangs between two consecutive gene 00 10 fragments which can subsequently be annealed and reamplified to generate a chimeric 0gene 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). A protease-encoding nucleic acid can be cloned into such an expression vector such that the fusion moiety is linked in-frame to the protease protein.

Functional equivalents The terms "functional equivalents" and "functional variants" are used interchangeably herein. Functional equivalents of a DNA according to the invention are isolated DNA fragments that encode a polypeptide that exhibits a particular function of an A. niger protease as defined herein. A functional equivalent of a polypeptide according to the invention is a polypeptide that exhibits at least one function of an A. niger protease as defined herein.

Functional protein or polypeptide equivalents may contain only conservative substitutions of one or more amino acids of a sequence selected from the group consisting of SEQ ID NO: 115 to SEQ ID NO: 171 or substitutions, insertions or deletions of non-essential amino acids. Accordingly, a non-essential amino acid is a residue that can be altered in a sequence selected from the group consisting of SEQ ID NO: 115 to SEQ ID NO: 171 without substantially altering the biological function. For example, amino acid residues that are conserved among the protease proteins of the present invention, are predicted to be particularly unamenable to alteration.

Furthermore, amino acids conserved among the protease proteins according to the present invention and other proteases are not likely to be amenable to alteration.

00 0 The term "conservative substitution" is intended to mean that a substitution in which the C amino acid residue is replaced with an amino acid residue having a similar side chain.

SThese families are known in the art and include amino acids with basic side chains S(e.g.lysine, arginine and hystidine), acidic side chains aspartic acid, glutamic acid), uncharged polar side chains glycine, asparagines, glutamine, serine, threonine, tyrosine, cysteine), non-polar side chains alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains threonine, valine, isoleucine) and aromatic side chains tyrosine, O phenylalanine tryptophan, histidine).

00 SFunctional nucleic acid equivalents may typically contain silent mutations or mutations that do not alter the biological function of encoded polypeptide. Accordingly, the invention provides nucleic acid molecules encoding protease proteins that contain changes in amino acid residues that are not essential for a particular biological activity.

Such prolease proteins differ in amino acid sequence from a sequence selected from the group consisting of SEQ ID NO: 115 to SEQ ID NO: 171 yet retain at least one biological activity. In one embodiment the isolated nucleic acid molecule comprises a nucleotide sequence encoding a protein, wherein the protein comprises a substantially homologous amino acid sequence of at least about 60%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or more homologous to the amino acid sequence shown in a sequence selected from the group consisting of SEQ ID NO: 115 to SEQ ID NO: 171.

For example, guidance concerning how to-make phenotypically silent amino acid substitutions is provided in Bowie, J.U. et al., Science 247:1306-1310 (1990) wherein the authors indicate that there are two main approaches for studying the tolerance of an amino acid sequence to change. The first method relies on the process of evolution, in which mutations are either accepted or rejected by natural selection. The second approach uses genetic engineering to introduce amino acid changes at specific positions of a cloned gene and selects or screens to identify sequences that maintain functionality. As the authors state, these studies have revealed that proteins are surprisingly tolerant of amino acid substitutions. The authors further indicate which changes are likely to be permissive at a certain position of the protein. For example, most buried amino acid residues require non-polar side chains, whereas few features of surface side chains are generally conserved. Other such phenotypically silent substitutions are described in Bowie et al, supra, and the references cited therein.

44 00

O

O

An isolated nucleic acid molecule encoding a protease protein homologous to the Sprotein selected from the group consisting of SEQ ID NO: 115 to SEQ ID NO: 171 can be created by introducing one or more nucleotide substitutions, additions or deletions into the coding nucleotide sequences according to a sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 57 or a sequence selected from the group consisting of SEQ ID NO: 58 to SEQ ID NO: 114 such that one or more amino acid C substitutions, deletions or insertions are introduced into the encoded protein. Such mutations may be introduced by standard techniques, such as site-directed 00 10 mutagenesis and PCR-mediated mutagenesis.

The term "functional equivalents" also encompasses orthologues of the A. niger protease protein. Orthologues of the A. niger protease protein are proteins that can be isolated from other strains or species and possess a similar or identical biological activity. Such orthologues can readily be identified as comprising an amino acid sequence that is substantially homologous to a sequence selected from the group consisting of SEQ ID NO: 115 to SEQ ID NO:-171.

As defined herein, the term "substantially homologous" refers to a first amino acid or nucleotide sequence which contains a sufficient or minimum number of identical or equivalent with similar side chain) amino acids or nucleotides to a second amino acid or nucleotide sequence such that the first and the second amino acid or nucleotide sequences have a common domain. For example, amino acid or nucleotide sequences which contain a common domain having about 60%, preferably 65%, more preferably 70%, even more preferably 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identity or more are defined herein as sufficiently identical.

Also, nucleic acids encoding other protease family members, which thus have a nucleotide sequence that differs from a sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 57 or a sequence selected from the group consisting of SEQ ID NO: 58 to SEQ ID NO: 114, are within the scope of the invention. Moreover, nucleic acids encoding protease proteins from different species which thus have a nucleotide sequence which differs from a sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 57 or a sequence selected from the group consisting of SEQ ID NO: 58 to SEQ ID NO: 114 are within the scope of the invention.

00 oo Nucleic acid molecules corresponding to variants natural allelic variants) and C-i homologues of the protease DNA of the invention can be isolated based on their Shomology to the protease nucleic acids disclosed herein using the cDNAs disclosed herein or a suitable fragment thereof, as a hybridisation probe according to standard hybridisation techniques preferably under highly stringent hybridisation conditions.

In addition to naturally occurring allelic variants of the protease sequence, the skilled t' person will recognise that changes can be introduced by mutation into the nucleotide -sequences of a sequence selected from the group consisting of SEQ ID NO: 1 to SEQ 00 seque10 ID NO: 57 or a sequence selected from the group consisting of SEQ ID NO: 58 to SEQ ID NO: 114 thereby leading to changes in the amino acid sequence of the protease protein without substantially altering the function of the protease protein.

In another aspect of the invention, improved protease proteins are provided. Improved protease proteins are proteins wherein at least one biological activity is improved. Such proteins may be obtained by randomly introducing mutations along all or part of the protease coding sequence, such as by saturation mutagenesis, and the resulting mutants can be expressed recombinantly and screened for biological activity. For instance, the art provides for standard assays for measuring the enzymatic activity of proteases and thus improved proteins may easily be selected.

In a preferred embodiment the protease protein has an amino acid sequence according to a sequence selected from the group consisting of SEQ ID NO: 115 to SEQ ID NO: 171. In another embodiment, the proteas&polypeptide is substantially homologous to the amino acid sequence according to a sequence selected from the group consisting of SEQ ID NO: 115 to SEQ ID NO: 171 and retains at least one biological activity of a polypeptide according to a sequence selected from the group consisting of SEQ ID NO: 115 to SEQ ID NO: 171, yet differs in amino acid sequence due to natural variation or mutagenesis as described above.

In a further preferred embodiment, the protease protein has an amino acid sequence encoded by an isolated nucleic acid fragment capable of hybridising to a nucleic acid according to a sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 57 or a sequence selected from the group consisting of SEQ ID NO: 58 to SEQ ID NO: 114, preferably under highly stringent hybridisation conditions.

V I 00 SAccordingly, the protease protein is a protein which comprises an amino acid sequence CN at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or Smore homologous to the amino acid sequence shown in a sequence selected from the group consisting of SEQ ID NO: 115 to SEQ ID NO: 171 and retains at least one functional activity of the polypeptide according to a sequence selected from the group consisting of SEQ ID NO: 115 to SEQ ID NO: 171.

Functional equivalents of a protein according to the invention can also be identified e.g.

Sby screening combinatorial libraries of mutants, e.g. truncation mutants, of the protein 00 10 of the invention for protease activity. In one embodiment, a variegated library of O variants is generated by combinatorial mutagenesis at the nucleic acid level. A variegated library of variants can be produced by, for example, enzymatically ligating a mixture of synthetic oligonucleotides into gene sequences such that a degenerate set of potential protein sequences is expressible as individual polypeptides, or alternatively, as a set of larger fusion proteins for phage display). There are a variety of methods that can be used to produce libraries of potential variants of the polypeptides of the invention from a degenerate oligonucleotide sequence. Methods for synthesizing degenerate oligonucleotides are known in the art (see, Narang (1983) Tetrahedron 39:3; Itakura et al. (1984) Annu. Rev. Biochem. 53:323; Itakura et al. (1984) Science 198:1056; Ike et al. (1983) Nucleic Acid Res. 11:477).

In addition, libraries of fragments of the coding sequence of a polypeptide of the invention can be used to generate a variegated population of polypeptides for screening a subsequent selection of varianfts. For example, a library of coding sequence fragments can be generated by treating a double stranded PCR fragment of the coding sequence of interest 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 S1 nuclease, and ligating the resulting fragment library into an expression vector. By this method, an expression library can be derived which encodes N-terminal and internal fragments of various sizes of the protein of interest.

Several techniques are known in the art for screening gene products of combinatorial libraries made by point mutations of truncation, and for screening cDNA libraries for gene products having a selected property. The most widely used techniques, which are 00 O amenable to high through-put analysis, for screening large gene libraries typically C include cloning the gene library into replicable expression vectors, transforming Sappropriate cells with the resulting library of vectors, 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 technique which enhances the frequency of functional mutants in the libraries, can be used in combination with the screening assays to identify n variants of a protein of the invention (Arkin and Yourvan (1992) Proc. Nail. Acad. Sci.

SUSA 89:7811-7815; Delgrave et al. (1993) Protein Engineering 6(3):327-331).

00 In addition to the protease gene sequence shown in a sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 57, it will be apparent for the person skilled in the art that DNA sequence polymorphisms that may lead to changes in the amino acid sequence of the protease protein may exist within a given population. Such genetic polymorphisms may exist in cells from different populations or within a population due to natural allelic variation. Allelic variants may also include functional equivalents.

Fragments of a polynucleotide according to the invention may also comprise polynucleotides not encoding functional polypeptides. Such polynucleotides may function as probes or primers for a PCR reaction. Such polynucleotides may also be useful when it is desired to abolish the functional activity of a protease in a particular organism (knock-out mutants).

Nucleic acids according to the invention irrespective of whether they encode functional or non-functional polypeptides, can be used as hybridization probes or polymerase chain reaction (PCR) primers. Uses of the nucleic acid molecules of the present invention that do not encode a polypeptide having a protease activity include, inter alia, isolating the gene encoding the protease protein, or allelic variants thereof from a cDNA library e.g. from other organisms than A. niger; in situ hybridization (e.g.

FISH) to metaphase chromosomal spreads to provide precise chromosomal location of the protease gene as described in Verma et al., Human Chromosomes: a Manual of Basic Techniques, Pergamon Press, New York (1988); Northern blot analysis for detecting expression of protease mRNA in specific tissues and/or cells and 4) probes and primers that can be used as a diagnostic tool to analyse the presence of a nucleic acid hybridisable to the protease probe in a given biological tissue) sample.

00 C-i Also encompassed by the invention is a method of obtaining a functional equivalent of Sa protease gene or cDNA. Such a method entails obtaining a labelled probe that includes an isolated nucleic acid which encodes all or a portion of the sequence according to a sequence selected from the group consisting of SEQ ID NO: 115 to SEQ ID NO: 171 or a variant thereof; screening a nucleic acid fragment library with the labelled probe under conditions that allow hybridisation of the probe to nucleic acid Sfragments in the library, thereby forming nucleic acid duplexes, and preparing a fullc-i length gene sequence from the nucleic acid fragments in any'labelled duplex to obtain 00 10 a gene related to the protease gene.

In one embodiment, a protease nucleic acid of the invention is at least 60%, 65%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more homologous to a nucleic acid sequence shown in a sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 57, a sequence selected from the group consisting of SEQ ID NO: 58 to SEQ ID NO: 114 or the complement thereof.

In another preferred embodiment a protease polypeptide of the invention is at least 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more homologous to the amino acid sequence shown in a sequence selected from the group consisting of SEQ ID NO: 115 to SEQ ID NO: 171.

Host cells In another embodiment, the invention features cells, transformed host cells or recombinant host cells that contain a nucleic acid encompassed by the invention. A "transformed cell" or "recombinant cell" is a cell into which (or into an ancestor of which) has been introduced, by means of recombinant DNA techniques, a nucleic acid according to the invention. Both prokaryotic and eukaryotic cells are included, e.g., bacteria, fungi, yeast, and the like, especially preferred are cells from filamentous fungi, in particular Aspergillus niger.

A host cell can be chosen that modulates the expression of the inserted sequences, or modifies and processes the gene product in a specific, desired fashion. Such modifications glycosylation) and processing cleavage) of protein products may facilitate optimal functioning of the protein.

00 (S Various host cells have characteristic and specific mechanisms for post-translational rprocessing and modification of proteins and gene products. Appropriate cell lines or host systems familiar to those of skill in the art of molecular biology and/or microbiology can be chosen to ensure the desired and correct modification and processing of the foreign protein expressed. To this end, eukaryotic host cells that possess the cellular machinery for proper processing of the primary transcript, glycosylation, and V' phosphorylation of the gene product can be used. Such host cells are well known in the Sart.

00 0Host cells also include, but are not limited to, mammalian cell lines such as CHO, VERO, BHK, HeLa, COS, MDCK, 293, 3T3, W138, and choroid plexus cell lines.

If desired, the polypeptides according to the invention can be produced by a stablytransfected cell line. A number of vectors suitable for stable transfection of mammalian cells are available to the public, methods for constructing such cell lines are also publicly known, in Ausubel et al. (supra); Antibodies The invention further features antibodies, such as monoclonal or polyclonal antibodies, that specifically bind protease proteins according to the invention.

As used herein, the term "antibody" (Ab) or "monoclonal antibody" (Mab) is meant to include intact molecules as well as antibody fragments (such as, for example, Fab and F(ab') 2 fragments) which are capable of specifically binding to protease protein. Fab and F(ab') 2 fragments lack the Fc fragment of intact antibody, clear more rapidly from the circulation, and may have less non-specific tissue binding of an intact antibody (Wahl et al., J. Nucl. Med. 24:316-325 (1983)). Thus, these fragments are preferred.

The antibodies of the present invention may be prepared by any of a variety of methods. For example, cells expressing the protease protein or an antigenic fragment thereof can be administered to an animal in order to induce the production of sera containing polyclonal antibodies. In a preferred method, a preparation of protease protein is prepared and purified to render it substantially free of natural contaminants.

Such a preparation is then introduced into an animal in order to produce polyclonal 00 O antisera of greater specific activity.

In the most preferred method, the antibodies of the present invention are monoclonal antibodies (or protease protein binding fragments thereof). Such monoclonal antibodies can be prepared using hybridoma technology (Kohler et al., Nature 256495 (1975); Kohler et al., Eur. J. Immunol. 6:511 (1976); Hammerling et al., In: Monoclonal Antibodies and T-Cell Hybridomas, Elsevier, pp. 563-681 (1981)). In general, such procedures involve immunizing an animal (preferably a mouse) with a protease Sprotein antigen or, with a protease protein expressing cell. The splenocytes of such Smice are extracted and fused with a suitable myeloma cell line. Any suitable myeloma 00 10 cell line may be employed in accordance with the present inventoin; however, it is Spreferably to employ the parent myeloma cell line (SP20), available from the American Type Culture Collection, Rockville, Maryland. After fusion, the resulting hybridoma cells are selectively maintained in HAT medium, and then cloned by limiting dilution as described by Wands et al. (Gastro-enterology 80.225-232 (1981)). The hybridoma cells obtained through such a selection are then assayed to identify clones which secrete antibodies capable of binding the protease protein antigen. In general, the polypeptides can be coupled to a carrier protein, such as KtH, as described in Ausubel et al., supra, mixed with an adjuvant, and injected into a host mammal.

In particular, various host animals can be immunized by injection of a polypeptide of interest. Examples of suitable host animals include rabbits, mice, guinea pigs, and rats.

Various adjuvants can be used to increase the immunological response, depending on the host species, including but not limited to Freund's (complete and incomplete), adjuvant mineral gels such as aluminum hydroxide, surface actve substances such as lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, keyhole limpet hemocyanin, dinitrophenol, BCG (bacille Calmette-Guerin) and Corynebacterium parvum. Polyclonal antibodies are heterogeneous populations of antibody molecules derived from the sera of the immunized animals.

Such antibodies can be of any immunoglobulin class including IgG, IgM, IgE, IgA, IgD, and any subclass thereof. The hybridomas producing the mAbs of this invention can be cultivated in vitro or in vivo.

Once produced, polyclonal or monoclonal antibodies are tested for specific recognition of an protease polypeptide or functional equivalent thereof in an immunoassay, such as a Western blot or immunoprecipitation analysis using standard techniques, as 00 O described in Ausubel et al., supra. Antibodies that specifically bind to protease proteins rC or functional equivalents thereof are useful in the invention. For example, such Santibodies can be used in an immunoassay to detect protease in pathogenic or non- Spathogenic strains of Aspergillus in Aspergillus extracts).

Preferably, antibodies of the invention are produced using fragments of the protease polypeptides that appear likely to be antigenic, by criteria such as high frequency of charged residues. For example, such fragments may be generated by standard Stechniques of PCR, and then cloned into the pGEX expression vector (Ausubel et al., 00 10 supra). Fusion proteins may then be expressed in E. coliand purified using a 0 glutathione agarose affinity matrix as described in Ausubel, et al., supra. If desired, several two or three) fusions can be generated for each protein, and each fusion can be injected into at least two rabbits. Antisera can be raised by injections in a series, typically including at least three booster injections. Typically, the antisera are checked for their ability to immunoprecipitate a recombinant protease polypeptide or functional equivalents thereof whereas unrelated proteins may serve as a control for the specificity of the immune reaction.

Alternatively, techniques decribed for the production of single chain antibodies (U.S.

Patent 4,946,778 and 4,704,692) can be adapted to produce single chain antibodies against a protease polypeptide or functional equivalents thereof. Kits for generating and screening phage display libraries are commercially available e.g. from Pharmacia.

Additionally, examples of methods and reagents particularly amenable for use in generating and screening antibody display library can be found in, for example, U.S.

Patent No. 5,223, 409; PCT Publication No. WO 92/18619; PCT Publication No. WO 91/17271; PCT Publication No. WO 20791; PCT Publication No. WO 92/20791; PCT Publication No. WO 92/15679; PCT Publication No. WO 93/01288; PCT Publication No. WO 92/01047; PCT Publication No. WO 92/09690; PCT Publication No. WO 90/02809; Fuchs et al. (1991) Bio/Technology 9:1370-1372; Hay et al. (1992) Hum.

Antibod. Hybridomas 3:81-85; Huse et al. (1989) Science 246;1275-1281; Griffiths et al. (1993) EMBO J. 12:725-734.

Polyclonal and monoclonal antibodies that specifically bind protease polypeptides of functional equivalents thereof can be used, for example, to detect expression of a protease gene or a functional equivalent thereof e.g. in another strain of Aspergillus.

00 O For example, protease polypeptide can be readily detected in conventional CN immunoassays of Aspergillus cells or extracts. Examples of suitable assays include, without limitation, Western blotting, ELISAs, radioimmune assays, and the like.

By "specifically binds" is meant that an antibody recognizes and binds a particular antigen, a protease polypeptide, but does not substantially recognize and bind Sother unrelated molecules in a sample.

SAntibodies can be purified, for example, by affinity chromatography methods in which 00 10 the polypeptide antigen is immobilized on a resin.

An antibody directed against a polypeptide of the invention monoclonal antibody) can be used to isolate the polypeptide by standard techniques, such as affinity chromatography or immunoprecipitation. Moreover, such an antibody can be used to detect the protein in a cellular lysate or cell supernatant) in order to evaluate the abundance and pattern of expression of the polypeptide. The antibodies can also be used diagnostically to monitor protein levels in'cells or tissue as part of a clinical testing procedure, to, for example, determine the efficacy of a given treatment regimen or in the diagnosis of Aspergillosis..

Detection can be facilitated by coupling the antibody to a detectable substance.

Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes-include horseradish peroxidase, alkaline phosphatase, P-galactosidase, or acetylcholinesterase; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive materials include 125, 1311, 35S or 3H.

Preferred epitopes encompassed by the antigenic peptide are regions that are located on the surface of the protein, hydrophilic regions. Hydrophobicity plots of the proteins of the invention can be used to identify hydrophilic regions.

The antigenic peptide of a protein of the invention comprises at least 7 (preferably 20, or 30) contiguous amino acid residues of the amino acid sequense of a S 1 t 00 O sequence selected from the group consisting of SEQ ID NO: 115 to SEQ ID NO: 171 rC and encompasses an epitope of the protein such that an antibody raised against the peptide forms a specific immune complex with the protein.

Preferred epitopes encompassed by the antigenic peptide are regions of protease that are located on the surface of the protein, hydrophilic regions, hydrophobic regions, alpha regions, beta regions, coil regions, turn regions and flexible regions.

Immunoassays 00 10 Qualitative or quantitative determination of a polypeptide according to the present 0 invention in a biological sample can occur using any art-known method. Antibodybased techniques provide special advantages for assaying specific polypeptide levels in a biological sample.

In these, the specific recognition is provided by the primary antibody (polyclonal or monoclonal) but the secondary detection system can utilize fluorescent, enzyme, or other conjugated secondary antibodies. As a result, an immunocomplex is obtained.

Accordingly, the invention provides a method for diagnosing whether a certain organism is infected with Aspergillus comprising the steps of: Isolating a biological sample from said organism suspected to be infected with Aspergillus, reacting said biological sample with an antibody according to the invention, determining whether immunecomptexes are formed.

Tissues can also be extracted, with urea and neutral detergent, for the liberation of protein for Western-blot or dot/slot assay. This technique can also be applied to body fluids.

Other antibody-based methods useful for detecting protease gene expression include immunoassays, such as the enzyme linked immunosorbent assay (ELISA) and the radioimmunoassay (RIA). For example, protease-specific monoclonal antibodies can be used both as an immunoabsorbent and as an enzyme-labeled probe to detect and quantify the protease protein. The amount of protease protein present in the sample can be calculated by reference to the amount present in a standard preparation using a 00 0 linear regression computer algorithm. In another ELISA assay, two distinct specific Smonoclonal antibodies can be used to detect protease protein in a biological fluid. In Sthis assay, one of the antibodies is used as the immuno-absorbent and the other as the Senzyme-labeled probe.

The above techniques may be conducted essentially as a "one-step" or "two-step" assay. The "one-step" assay involves contacting protease protein with immobilized antibody and, without washing, contacting the mixture with the labeled antibody. The 0 "two-step" assay involves washing before contacting the mixture with the labeled 00 10 antibody. Other conventional methods may also be employed as suitable. It is usually O desirable to immobilize one component of the assay system on a support, thereby allowing other components of the system to be brought into contact with the component and readily removed from the sample.

Suitable enzyme labels include, for example, those from the oxidase group, which catalyze the production of hydrogen peroxide by reacting with substrate. Activity of an oxidase label may be assayed by measuring the concentration of hydrogen peroxide formed by the enzyme-labelled antibody/substrate reaction.

Besides enzymes, other suitable labels include radioisotopes, such as iodine (1251, 1211), carbon sulphur 35 tritium 3 indium 11 2 1n), and technetium 99 mTc), and fluorescent labels, such as fluorescein and rhodamine, and biotin.

Specific binding of a test compound to a potease polypeptide can be detected, for example, in vitro by reversibly or irreversibly immobilizing the protease polypeptide on a substrate, the surface of a well of a 96-well polystyrene microtitre plate. Methods for immobilizing polypeptides and other small molecules are'well known in the art. For example, the microtitre plates can be coated with a protease polypeptide by adding the polypeptide in a solution (typically, at a concentration of 0.05 to 1 mg/ml in a volume of 1-100 ul) to each well, and incubating the plates at room temperature to 37 OC for 0.1 to 36 hours. Polypeptides that are not bound to the plate can be removed by shaking the excess solution from the plate, and then washing the plate (once or repeatedly) with water or a buffer. Typically, the polypeptide is contained in water or a buffer. The plate is then washed with a buffer that lacks the bound polypeptide. To block the free protein-binding sites on the plates, the plates are blocked with a protein that is unrelated to the bound polypeptide. For example, 300 ul of bovine serum albumin 00 0 (BSA) at a concentration of 2 mg/ml in Tris-HCI is suitable. Suitable substrates include those substrates that contain a defined cross-linking chemistry plastic substrates, Ssuch as polystyrene, styrene, or polypropylene substrates from Corning Costar Corp.

S(Cambridge, MA), for example). If desired, a beaded particle, beaded agarose or beaded sepharose, can be used as the substrate.

Binding of the test compound to the polypeptides according to the invention can be V'C detected by any of a variety of artknown methods. For example, a specific antibody can Sbe used in an immunoassay. If desired, the antibody can be labeled fluorescently 00 10 or with a radioisotope) and detected directly (see, West and McMahon, J. Cell 0Biol. 74:264, 1977). Alternatively, a second antibody can be used for detection a labeled antibody that binds the Fc portion of an anti-AN97 antibody). In an alternative detection method, the protease polypeptide is labeled, and the label is detected by labeling aprotease polypeptide with a radioisotope, fluorophore, chromophore, or the like). In still another method, the protease polypeptide is produced as a fusion protein with a protein that can be detected optically, green fluorescent protein (which can be detected under UV light). In an-alternative method, the protease polypeptide can be covalently attached to or fused with an enzyme having a detectable enzymatic activity, such as horse radish peroxidase, alkaline phosphatase, agalactosidase, or glucose oxidase. Genes encoding all of these enzymes have been cloned and are readily available for use by those of skill in the art. If desired, the fusion protein can include an antigen, and such an antigen can be detected and measured with a polyclonal or monoclonal antibody using conventional methods. Suitable antigens include enzymes horse radish peroxidase, alkaline phosphatase, and agalactosidase) and non-enzymatic polypeptides serum proteins, such as BSA and globulins, and milk proteins, such as caseins).

Epitopes, antigens and immunoqens.

In another aspect, the invention provides a peptide or polypeptide comprising an epitope-bearing portion of a polypeptide of the invention. The epitope of this polypeptide portion is an immunogenic or antigenic epitope of a polypeptide of the invention. An "immunogenic epitope" is defined as a part of a protein that elicits an antibody response when the whole protein is the immunogen. These immunogenic epitopes are believed to be confined to a few loci on the molecule. On the other hand, a region of a protein molecule to which an antibody can bind is defined as an "antigenic 00 epitope." The number of immunogenic epitopes of a protein generally is less than the number of antigenic epitopes. See, for instance, Geysen, H. M. et al., Proc. Natl. Acad.

SSci. USA 81:3998-4002 (1984).

As to the selection of peptides or polypeptides bearing an antigenic epitope that contain a region of a protein molecule to which an antibody can bind), it is well known Sin that art that relatively short synthetic peptides that mimic part of a protein sequence Vn are routinely capable of eliciting an antiserum that reacts with the partially mimicked Sprotein. See, for instance, Sutcliffe, J. G. et al., Science 219:660-666 (1984). Peptides 00 10 capable of eliciting protein-reactive sera are frequently represented in the primary 0sequence of a protein, can be characterized by a set of simple chemical rules, and are confined neither to immunodominant regions of intact proteins immunogenic epitopes) nor to the amino or carboxyl terminals. Peptides that are extremely hydrophobic and those of six or fewer residues generally are ineffective at inducing antibodies that bind to the mimicked protein; longer, soluble peptides, especially those containing proline residues, usually are effective. Sutcliffe et al., supra For instance; 18 of 20 peptides designed according to these guidelines, containing 8-39 residues covering 75% of the sequence of the influenza virus hemagglutinin HAI polypeptide chain, induced antibodies that reacted with the HA1 protein or intact virus; and 12/12 peptides from the MuLV polymerase and 18/18 from the rabies glycoprotein induced antibodies that precipitated the respective proteins.

Antigenic epitope-bearing peptides and polypeptides of the invention are therefore useful to raise antibodies, including monoelonal antibodies, that bind specifically to a polypeptide of the invention. Thus, a high proportion of hybridomas obtained by fusion of spleen cells from donors immunized with an antigen epitope-bearing peptide generally secrete antibody reactive with the native protein. Sutcliffe et al., supra, at 663. The antibodies raised by antigenic epitope bearing peptides or polypeptides are useful to detect the mimicked protein, and antibodies to different peptides may be used for tracking the fate of various regions of a protein precursor which undergoes posttranslation processing. The peptides and anti-peptide antibodies may be used in a variety of qualitative or quantitative assays for the mimicked protein, for instance in competition assays since it has been shown that even short peptides about 9 amino acids) can bind and displace the larger peptides in immunoprecipitation assays.

See, for instance, Wilson, I.A. et al., Cell 37:767-778 at 777 (1984). The anti-peptide antibodies of the invention also are useful for purification of the mimicked protein, for 00 Sinstance, by adsorption chromatography using methods well known in the art.

SAntigenic epitope-bearing peptides and polypeptides of the invention designed Saccording to the above guidelines preferably contain a sequence of at least seven, more preferably at least nine and most preferably between about 15 to about 30 amino acids contained within the amino acid sequence of a polypeptide of the invention.

However, peptides or polypeptides comprising a larger portion of an amino acid sequence of a polypeptide of the invention, containing about 30 to about 50 amino O acids, or any length up to and including the entire amino acid sequence of a 00 10 polypeptide of the invention, also are considered epitope-bearing peptides or O polypeptides of the invention and also are useful for inducing antibodies that react with the mimicked protein. Preferably, the amino acid sequence of the epitope-bearing peptide is selected to provide substantial solubility in aqueous solvents the sequence includes relatively hydrophilic residues and highly hydrophobic sequences are preferably avoided); and sequences containing proline residues are particularly preferred.

The epitope-bearing peptides and polypeptides of the invention may be produced by any conventional means for making peptides or polypeptides including recombinant means using nucleic acid molecules of the invention. For instance, a short epitopebearing amino acid sequence may be fused to a larger polypeptide which acts as a carrier during recombinant production and purification, as well as during immunization to produce anti-peptide antibodies.

Epitope-bearing peptides also may be synthesized using known methods of chemical synthesis. For instance, Houghten has described a simple method for synthesis of large numbers of peptides, such as 10-20 mg of 248 different 13 residue peptides representing single amino acid variants of a segment of the HAl polypeptide which were prepared and characterized (by ELISA-type binding studies) in less than four weeks. Houghten, R. Proc. Natl. Acad. Sci. USA 82:5131-5135 (1985). This "Simultaneous Multiple Peptide Synthesis (SMPS)" process is further described in U.S.

Patent No. 4,631,211 to Houghten et al. (1986). In this procedure the individual resins for the solid-phase synthesis of various peptides are contained in separate solventpermeable packets, enabling the optimal use of the many identical repetitive steps involved in solid-phase methods.

00 0 A manual procedure allows 500-1000 or more syntheses to be conducted C-i simultaneously. Houghten et al., supra, at 5134.

Epitope-bearing peptides and polypeptides of the invention are used to induce antibodies according to methods well known in the art. See, for instance, Sutcliffe et al., supra; Wilson et al., supra; Chow, M. et al., Proc. Natl. Acad. Sci. USA 82:910-914; and Bittle, F.J. et al., J. Gen. Virol. 66:2347-2354 (1985).

i3 O Generally, animals may be immunized with free peptide; however, anti-peptide 00 10 antibody titer may be boosted by coupling of the peptide to a macromolecular carrier, Ssuch as keyhole limpet hemocyanin (KLH) or tetanus toxoid. For instance, peptides containing cysteine may be coupled to carrier using a linker such as maleimidobenzoyl- N-hydroxysuccinimide ester (MBS), while other peptides may be coupled to carrier using a more general linking agent such as glutaraldehyde.

Animals such as rabbits, rats and mice are immunized with either free or carriercoupled peptides, for instance, by intraperitoneal and/or intradermal injection of emulsions containing about 100 ug peptide or carrier protein and Freund's adjuvant. Several booster injections may be needed, for instance, at intervals of about two weeks, to provide a useful titer of anti-peptide antibody which can be detected, for example, by ELISA assay using free peptide adsorbed to a solid surface. The titer of anti-peptide antibodies in serum from an immunized animal may be increased by selection of antipeptide antibodies, for instance, by adsorption to the peptide on a solid support and elution of the selected antibodies according to methods well known in the art.

Immunogenic epitope-bearing peptides of the invention, those parts of a protein that elicit an antibody response when the whole protein is the immunogen, are identified according to methods known in the art. For instance, Geysen et al., 1984, supra, discloses a procedure for rapid concurrent synthesis on solid supports of hundreds of peptides of sufficient purity to react in an enzyme-linked immunosorbent assay. Interaction of synthesized peptides with antibodies is then easily detected without removing them from the support. In this manner a peptide bearing an immunogenic epitope of a desired protein may be identified routinely by one of ordinary skill in the art. For instance, the immunologically important epitope in the coat protein of foot-and-mouth disease virus was located by Geysen et al. with a resolution of seven amino acids by synthesis of an overlapping set of all 208 possible hexapeptides 59 0 covering the entire 213 amino acid sequence of the protein. Then, a complete replacement set of peptides in which all 20 amino acids were substituted in turn at every position within the epitope were synthesized, and the particular amino acids conferring specificity for the reaction with antibody were determined. Thus, peptide analogs of the epitope-bearing peptides of the invention can be made routinely by this method. U.S. Patent No. 4,708,781 to Geysen (1987) further describes this method of identifying a peptide bearing an immunogenic epitope of a desired protein.

SFurther still, U.S. Patent No. 5,194,392 to Geysen (1990) describes a general method 00 10 of detecting or determining the sequence of monomers (amino acids or other 0compounds) which is a topological equivalent of the epitope a "mimotope") which is complementary to a particular paratope (antigen binding site) of an antibody of interest. More generally, U.S. Patent No. 4,433,092 to Geysen (1989) describes a method of detecting or determining a sequence of monomers which is a topographical equivalent of a ligand which is complementary to the ligand binding site of a particular receptor of interest. Similarly, U.S. Patent No. 5,480,971 to Houghten, R. A. et al.

(1996) on Peralkylated Oligopeptide Mixtures discloses linear C1-C7-alkyl peralkylated oligopeptides and sets and libraries of such peptides, as well as methods for using such oligopeptide sets and libraries for determining the sequence of a peralkylated oligopeptide that preferentially binds to an acceptor molecule of interest. Thus, nonpeptide analogs of the epitope-bearing peptides of the invention also can be made routinely by these methods.

Removal or reduction of protease activity The present invention also relates to methods for producing a mutant cell of a parent cell, which comprises disrupting or deleting a nucleic acid sequence encoding the protease or a control sequence thereof, which results in the mutant cell producing less of the protease than the parent cell.

The construction of strains which have reduced protease activity may be conveniently accomplished by modification or inactivation of a nucleic acid sequence necessary for expression of the protease activity in the cell. The nucleic acid sequence to be modified or inactivated may be, for example, a nucleic acid sequence encoding the protease or a part thereof essential for exhibiting protease activity, or the nucleic acid sequence may have a regulatory function required for the expression of the protease 00 O from the coding sequence of the nucleic acid sequence. An example of such a CN regulatory or control sequence may be a promoter sequence or a functional part Sthereof, a part which is sufficient for affecting expression of the protease. Other control sequences for possible modification include, but are not limited to, a leader, a polyadenylation sequence, a propeptide sequence, a signal sequence, and a termination site.

Modification or inactivation of the nucleic acid sequence may be performed by 0 subjecting the cell to mutagenesis and selecting for cells in which the protease 00 10 producing capability has been reduced or eliminated. The mutagenesis, which may be Sspecific or random, may be performed, for example, by use of a suitable physical or chemical mutagenizing agent, by use of a suitable oligonucleotide, or by subjecting the DNA sequence to PCR generated mutagenesis. Furthermore, the mutagenesis may be performed by use of any combination of these mutagenizing agents.

Examples of a physical or chemical mutagenizing agent suitable for the present purpose include ultraviolet (UV) irradiation, hydroxylamine: N-methyl-N'-nitro-Nnitrosoguanidine (MNNG), O-methyl hydroxylamine, nitrous acid, ethyl methane sulphonate (EMS), sodium bisulphite, formic acid, and nucleotide analogues.

When such agents are used, the mutagenesis is typically performed by incubating the cell to be mutagenized in the presence of the mutagenizing agent of choice under suitable conditions, and selecting for cells exhibiting reduced or no expression of protease activity.

Modification or inactivation of production of a protease of the present invention may be accomplished by introduction, substitution, or removal of one or more nucleotides in the nucleic acid sequence encoding the protease or a regulatory element required for the transcription or translation thereof. For example, nucleotides may be inserted or removed so as to result in the introduction of a stop codon, the removal of the start codon, or a change of the open reading frame. Such modification or inactivation may be accomplished by site-directed mutagenesis or PCR generated mutagenesis in accordance with methods known in the art.

Although, in principle, the modification may be performed in vivo, directly on the cell expressing the nucleic acid sequence to be modified, it is preferred that the modification be performed in vitro as exemplified below.

An example of a convenient way to inactivate or reduce production by a host cell of 0o choice is based on techniques of gene replacement or gene interruption. For example, in the gene interruption method, a nucleic acid sequence corresponding to the endogenous gene or gene fragment of interest is mutagenized in vitro to produce a Sdefective nucleic acid sequence which is then transformed into the host cell to produce a defective gene. By homologous recombination, the defective nucleic acid sequence replaces the endogenous gene or gene fragment. It may be desirable that the defective gene or gene fragment also encodes a marker which may be used for selection of transformants in which the gene encoding the protease has been modified Sor destroyed.

(N

00 0Alternatively, modification or inactivation of the nucleic acid sequence encoding a protease of the present invention may be performed by established anti-sense techniques using a nucleotide sequence complementary to the protease encoding sequence. More specifically, production of the protease by a cell may be reduced or eliminated by introducing a nucleotide sequence complementary to the nucleic acid sequence encoding the protease which may be transcribed in the cell and is capable of hybridizing to the protease mRNA produced irrthe cell. Under conditions allowing the complementary antisense nucleotide sequence to hybridize to the protease mRNA, the amount of protease translated is thus reduced or eliminated.

It is preferred that the cell to be modified in accordance with the methods of the present invention is of microbial origin, for example, a fungal strain which is suitable for the production of desired protein products, either homologous or heterologous to the cell.

The present invention further relates to a mutant cell of a parent cell which comprises a disruption or deletion of a nucleic acid sequence encoding the protease or a control sequence thereof, which results in the mutant cell producing less of the protease than the parent cell.

The protease-deficient mutant cells so created are particularly useful as host cells for the expression of homologous and/or heterologous polypeptides. Therefore, the present invention further relates to methods for producing a homologous or heterologous polypeptide comprising culturing the mutant cell under conditions conducive for production of the polypeptide; and recovering the polypeptide. In the present context, the term "heterologous polypeptides" is defined herein as polypeptides which are not native to the host cell, a native protein in which modifications have been 00 0 made to alter the native sequence, or a native protein whose expression is C-i quantitatively altered as a result of a manipulation of the host cell by recombinant DNA Stechniques.

The methods of the present invention for producing an essentially protease-free product is of particular interest in the production of eukaryotic polypeptides, in particular fungal proteins such as enzymes. The protease-deficient cells may also be used to express heterologous proteins of interest for the food industry, or of pharmaceutical interest.

00 SUse of proteases in industrial processes The invention also relates to the use of the protease according to the invention in a selected number of industrial and pharmaceutical processes. Despite the long term experience obtained with these processes, the protease according to the invention features a number of significant advantages over the enzymes currently used.

Depending on the specific application, these advantages can include aspects like lower production costs, higher specificity towards the substrate, less antigenic, less undesirable side activities, higher yields when produced in a suitable microorganism, more suitable pH and temperature ranges, better tastes of the final product as well as food grade and kosher aspects.

In large scale industrial applications aimed at food or feed production, proteolytic enzymes are commonly used to improve aspects like protein solubility, extraction yields, viscosity or taste, texture, nutritional value, minimalisation of antigenicity or antinutrional factors, colour or functionality as well as processing aspects like filterablity of the proteinaceous raw material. In these applications the proteinaceous raw material can be of animal or vegetable origin and examples include vegetable proteins such as soy protein, wheat gluten, rape seed protein, pea protein, alfalfa protein, sunflower protein, fabaceous bean protein, cotton or sesame seed protein, maize protein, barley protein, sorghum protein, potato protein, rice protein, coffee proteins, and animal derived protein such as milk protein casein, whey protein), egg white, fish protein, meat protein including gelatin, collagen, blood protein haemoglobin), hair, feathers and fish meal.

An important aspect of the proteases according to the invention is that they cover a 00 0 whole range of pH and temperature optima which are ideally suited for a variety of NC applications. For example many large scale processes benefit from relatively high Sprocessing temperatures of 50 degrees C or higher to control the risks of microbial Sinfections. Several proteases according to the invention comply with this demand but at the same time exhibit no extreme heat stabilities so that they resist attempts to inactivate the enzyme by an additional heat treatment. The latter feature allows production routes that yield final products free of residual proteolytic activity. Similarly l many feed and food products have slightly acidic pH values so that for their processing Sproteases with acidic or near neutral pH optima are preferred. A protease according to 00 10 the invention complies with this requirement as well.

The specificity of endoproteases is usually defined in terms of preferential cleavages of bonds between the carboxyl of the amino acid residue in position P1 and the amino group of the residue in position P1' respectively. The preference may be conditioned predominantly either by P1 positively charged residues in substrates for trypsin), by P1'(e.g. hydrophobic residues in cleavages by thermolysin) or by both P1 and P2 specific cleavages between two positively charged residues by adrenal medulla serine endoprotease). In some cases more distant residues may determine the cleavage preference, e.g. P2 for streptococcal peptidase A. Some residues are known to influence cleavages negatively; it is well known that bonds with proline in position P1'are resistant to the action of many proteases. Most endoproteases cleave preferentially either in a hydrophobic environment or in the proximity of negatively charged residues. For example, industrially available endoproteases like chymotrypsin (obtained from bovine pancreas) or subtilisin, neutral metallo endoprotease or thermolysin (all obtained from Bacillus species) tend to favour cleavage "behind" hydrophobic amino acids like -Phe, -Leu and -Tyr. Other industrially available endoproteases are trypsin (obtained from bovine pancreas) preferring cleavage behind -Arg and -Lys and papain (a complex mixture of various enzymes including proteases obtained from papaya fruits) preferring cleavage behind -Arg.

In contrast, peptide bonds formed by small sized residues such as Ala, Gly, Ser, Thre as well as lie and Pro are poor substrates (Keil, B et al.; Protein Seq Data Anal (1993) 401-407). This situation has a profound implications for the pharmaceutical, the food and beverages, the agro and even the chemical industry. A protease according to the invention exhibits uncommon cleavage preferences.

00 0 The exopeptidases act only near the ends of polypeptide chains. Those acting at a free N-terminus liberate a single amino acid residue (socalled aminopeptidases) or a Sdipeptide or a tripeptide (socalled dipeptidyl-peptidases and tripeptidyl-peptidases) SThose acting at a free C-terminus liberate a single residu (socalled carboxypeptidases) or a dipeptide (socalled peptidyl-dipeptidases) The carboxypeptidases are allocated to three groups on the basis of catalytic mechanism i.e. serine-type carboxypeptidases, metallocarboxypeptidases and cystein-type carboxypeptidases. Other exopeptidases are specific for dipeptides (socalled dipeptidases) or are able to cleave peptide Slinkages other than those of alpha-carboxyl or alpha- amino groups socalled omega 00 10 peptidases). Examples of such new omega peptidases are the pyroglutamyl-peptidase Sand the acylaminoacyl-peptidase as identified in the present invention (see Tablel, genes 18 and 45 respectively).

Typical examples of industrial application which depend on the use of pure endoproteases and in which the protease according to the invention can be expected to deliver a superior performance include the processing of materials of vegetable or animal origin. These processing steps can be-aimed at modifying a large array of characteristics of either the crude material or the (partially) purified protein fraction. For example, these processing steps can be aimed at maximising product solubilities, filterabilities, separabilities, protein extraction yields and digestibilities or minimising toxicities, off-tastes and viscosities. Furthermore the treatment can be directed at altering physico-chemical characteristics of the crude material or the purified (or partially purified protein. These advantages apply not only if the endoprotease according to the invention is applied as a-processing aid in industrial applications but also if applied as an active enzyme component in animal feed. Specifically the endoprotease according to the invention can be applied as bread improver in the bakery industry, e.g. to retard the staling of bread or to diminishing the viscosity of doughs. Or the endoprotease can be used in the beer and wine industry to prevent or to minimise the formation of undesirable protein hazes. Alternatively it can be used in the beer industry to optimise the protein extraction yields of cereals used in the preparation of the wort. Furthermore, it can also be advantageously used in the dairy industry as a milk clotting agent with superior characteristics or to optimise the texturising, foaming or setting characteristics of various milk components. Another application in the dairy industry is the use of the new protease in the preparation of Enzyme Modified Cheeses (EMC's).

00

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SMoreover, various proteinaceous substrates can be subjected to an endoprotease according to the invention, usually in combination with other proteolytic enzymes to Sobtain hydrolysates for medical or non- medical applications. Here the endoprotease according to the invention is surprisingly effective in achieving a complete hydrolysis of the proteinaceous substrate so that even protease resistant parts are fully hydrolysed, the endoprotease is also surprisingly active in minimising the allergenicity of the final V) hydrolysate or in suppressing the formation of bitter off-tastes.

00 10 More specifically the endoprotease according to the invention is characterised by its Spreference for cleaving proteins at unusual peptide bonds, especially with the small size amino acid residues of Ala, Gly, Ser and Thr, or the residues lie and Pro in either the P1 or the P1' position (Keil, B et al.; Protein Seq Data Anal (1993) 5; 401-407). As the result those fractions of the proteinaceous starting materials that resist hydrolysis upon using prior art endoproteases, can be dissolved and hydrolysed using the endoprotease according to the invention. Non limiting examples of such protease resistant fractions include socalled extensinsin plant materials and collagen, gelatin but also specific milk components in material of animal origen.

Various feedstuffs such as e.g. soybeans contain trypsin inhibitors. These proteins inhibit trypsin activity in the GI-tract of e.g. pigs and poultry. This trypsin inhibiting activity results in sub-optimal protein digestibility in these animals resulting in increased waste production and poor economics. This problem may partly be overcome by toasting soybeans at high temperatures. Two different types of trypsin inhibitors have been identified in soybeans, i.e. the Bowman-Birk type trypsin inhibitors and the Kunitz type trypsin inhibitors.

This invention now provides an alternative way to degrade trypsin inhibiting activity over toasting, in that it provides a cysteine proteases (EC 3.4.22, table 1) capable of cleaving at Leucinel 76-Aspartatel77 peptide bond near the carboxyl-terminus of the Kunitz type trypsin inhibitor (as reviewed by Wilson (1988) in CRC Critical Reviews in Biotechnology 8 197-216). This results in inactivation of this trypsin inhibitor in soybean. It was surprisingly found that the cysteine proteases secreted by the fungus Aspergillus niger fulfilled these criteria far better than similar enzymes derived from other organisms.

00 Proteases are also widely used in the art of cheese-making. In the production of Scheese it is necessary to coagulate the cheese milk to be able to separate the cheese Smatters e.g. casein from the whey. Several milk coagulating enzymes, also referred to Sas coagulants, have been described and include (bovine) chymosin, bovine pepsin, porcine pepsin as well as microbial enzymes like Rhizomucor miehei protease, Rhizomucor pusillus protease and Cryptonectria parasitica protease. Chymosin can be obtained from calf stomachs but can also be produced microbially by for example SKluyveromyces lactis. All these enzymes are characterized by having specificity for the Speptide bond between residue 105 (phenylalanine) and residue 106 (methionine) or the 00 10 bond adjacent to that in K-casein. This means that by employing these enzymes in Scheese making, the K-casein is split at the junction between para-K-casein and the macro-peptide moiety called glycomacropeptide (GMP) carrying the negative charges.

When this occurs the macropeptide diffuses into the whey, its stabilizing effect on the solubility of the casein micelles is lost, and the casein micelles can start to aggregate once sufficient kappa-casein has been hydrolyzed. For further elaboration on the enzymatic coagulation of milk e.g. D.G. Dalaleish in Advanced Dairy Chemistry vol.1 ed by P.F. Fox, Elsevier, London, 1992.

The currently available coagulants allow for a rather high yield of cheese, however, it should be realised that due to the enormous volumes of cheese produced, an increased yield in the order of magnitude of tenths of percent points may constitute a substantial economical advantage. Consequently there is a great need in the art for coagulants with an (even slightly) improved yield.

Coagulants are characterized by their high substrate specificity, which is, however, dependent on pH and temperature. In a typical cheese making process the pH will change from the initial pH 6.3 to lower pH values in the range of 4.5-5.5, the end-value depends on the conditions used during the cheese production process.

Some coagulants are more sensitive to pH changes than others. The Rhizomucor pusillus protease for example is more sensitive to pH changes than chymosin. Besides pH, also other parameters like temperature and water content may affect the protease specificity. It is well known that most coagulants show a changing substrate specificity with changing pH, resulting in altered proteolytic activity in later stages of the cheese making process. It is also well known that coagulants differ in the extent of casein proteolysis; they may also show differences in the peptide patterns produced during 00 proteolysis. These are relevant factors during cheese ripening and may affect cheese properties like taste, flavor and texture. In some cases coagulants give rise to undesired effects like the formation of bitter tasting peptides or off-taste. In addition, changes in proteolytic specificity may lead to a reduction in yield. Pepsin, a well known component in many bovine chymosin preparations, is an example of a protease that gives rise to lower yields and taste effects as compared to pure chymosin. There is still n a need for coagulants with give rise to new, improved cheese texture and taste. Such Snew coagulants result in the accelerated development of taste and texture profiles Crelated to cheese aging, therewith providing a substantial economical benefit.

00 0 SIt is well known that free amino acids are very important in taste and flavour generation.

Especially the amino acids leucine, phenylalanine, methionine and valine play an important role in the generation of typical cheese taste and flavor components. The free amino acids are converted via fermentation by micro organisms that are added during the cheese manufacturing process into the actual flavor and taste generating compounds like methanediol, dimethyldisulphide, methylpropanoic acid and methylpropanal. Exo-peptidases play an important role in the generation of free amino acids. They can only be effective, however, when they are combined with an endoprotease of appropriate specificity. Appropriate combinations of exo- and endopeptidases can be used in cheese making, resulting in the manufacture of cheeses with new and improved taste profiles.

The enzymes according to the invention may be used to hydrolyze proteinaceous materials of animal origin such as whole milk, skim milk, casein, whey protein or mixtures of casein and whey protein. Such mixtures of casein and whey protein may be used, for example, in ratios similar to those found in human milk. Furthermore, the enzyme mixture according to the invention may be used to hydrolyze proteinaceous materials of plant origin such as, for example, wheat gluten malted or unmalted barley or other cereals used for making beer, soy milk, concentrates or isolates thereof, maize protein concentrates and isolates thereof, and rice proteins.

Within the area of large scale industrial processes, some applications rely on the use of endoproteases only whereas in other applications combinations of endoproteases with exoproteases are essential. Typical examples which depend on the use of pure endoproteases and in which the protease according to the invention can deliver a I 00 O superior performance include applications like the processing of soy or peas or cereals

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proteins aimed at minimising viscosities or optimising foaming or other physics- Schemical characteristics, bread improvers in the bakery industry also aimed at Sdiminishing the viscosity of doughs, processing aids in the beer and wine industry aimed at the prevention of protein hazes or optimising the extraction yields of cereals, feed additives in the bio industry aimed at enhancing intestinal absorption or in modulating microbial activities in the gut, processing aids in the dairy industry aimed at C optimising the clotting, foaming or setting characteristics of various milk components.

C Moreover, v For specific market segments proteins derived from milk or soy or 10 collagen are exposed to proteases to produce socalled protein hydrolysates. Although Sthe main outlets for these protein hydrolysates are infant formula and food products for hospitalised persons, products intended for persons with non-medical needs, such as athletes or people on a slimming diet form a rapidly growing segment. In all of these applications protein hydrolysates offer attractive advantages such as lowered allergenicities, facilitated gastro-intestinal uptake, less chemical deterioration of desirable amino acids like glutamine and cystein and finally, absence of proteinaceous precipitations in acid beverages during prolonged storage periods. All these advantages can be combined if the hydrolysate is offered as a mixture of di- and tripeptides. However, currently all commercially available hydrolysates are produced by combining several endoproteases. The latter approach implies a non-uniform and incomplete degradation of the protein. To obtain the desired mixture of di- and tripeptides, a hydrolysis process involving a combination of various di-and tripeptidylpeptidases would be ideal. Unfortunately, only few of these enzymes from food grade and industrially acceptable microorganisms are known, let alone industrially available. According to the invention several of highly useful di- and tripeptidylpeptidases are economically obtainable in a relatively pure state. Preferred are those di- or tripeptidylpeptidases that exhibit a low selectivity towards the substrate to be cleaved, i.e. exhibit minimal amino acid residue cleavage preferences only.

Preferred are combinations of those di- or tripeptidylpeptidases that hydrolyse high percentage of the naturally occurring peptide bonds. Despite this high activity to naturally occurring peptide bonds, a total hydrolysis to free amino acids is prevented by the nature of the di-and tripeptidylpeptidases. Also preferred are those di- or tripeptidylpeptidases that are optimally active between pH 4 to 8 and exhibit adequate temperature stability. Adequate temperature stability implies that at least preferably at least 60%, more preferably between 70 and 100% of the initial hydrolytic activity survives after heating the enzyme together with the substrate for 1 hour at 00 O degrees C.

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Although the process towards an efficiebnt production of mixtures di-or tripeptides or Sdi-and tripeptides hinges on the availability of the enzymes according to the invention, Sthe first enzyme incubation with the proteinaceous substrate will usually be an endoprotease. Preferably an endoprotease with a broad spectrum endopeptidase suited for the situation, e.g. subtilisin (Delvolase from DSM), neutral metallo protease S(Neutrase from NOVO) or thermolysin (Thermoase from Daiwa Kasei) for the near C neutral conditions and pepsin or aspergillopepsin Sumizyme AP from Shin Nihon, Japan) for the acidic conditions. Aim of this first digestion is to improve the solubility, to 00 10 reduce the viscosity and to reduce the heat setting characteristics of the water/protein Smixture. Furthermore this pretreatment with an endonuclease is essential to create enough starting points for the di- and tripeptidylpeptidases hereby accellerating the proces of di- or tripeptide formation. Optionally a protease intended for debittering of the hydrolysate can be included in this stage of the process or later, together with the di-or tripeptidylpeptidases.

Main aim of the latter hydrolysates is to minimize the allergenicity of the product or to facilitate gastro-intestinal uptake. In the production of such hydrolysates the use of dipeptidyl- and tripeptidyl-peptidases is of special importance as hese s offer an efficient way for producing hydrolysates..

Other applications in these food and feed industries totally rely upon combinations of one or more endoprotease(s) with one or more exoprotease(s). Such combinations of an endoprotease with an exoprotease are typically used in industries to improve aspects like taste and colour of the final product. The reason for this is that the development of taste and colour is largely dependent upon the presence of free amino acids. Free amino acids can not only be obtained by exoproteases such as carboxypeptidases and aminopeptidases but also by peptidyl-dipeptidases. If combined with endoproteases or even dipeptidyl-or tripeptidyl-peptidases, carboxypeptidases, aminopeptidases and peptidyl-dipeptidases can create larger quantities of free amino acids in less time. However, in all of these processes an uncontrolled release of amino acids or even non-proteinaceous components should be avoided to minimise undesirable side reactions.

Though free amino acids as such, can elicit a number of taste impressions, these taste impressions are very basic (bitter, sweet, sour and "umami") and the amino acid 00 O concentration required for perceiving these tastes are high. Despite these high threshold values, free amino acids are able to create major sensory effects at much lower concentration ranges through a number of flavour enhancing mechanisms. One of these mechanism involves the combination of free amino acids with sugars in socalled Maillard reactions. Compared with free amino acids, with these Maillard products overwhelmingly complex flavour and odour systems can develop with threshold values Sthat are several orders of magnitude lower than those recorded for the free amino Sacids. Maillard products are formed at elevated temperatures usually during cooking, Sbaking or roasting when preparing food or feed products. During these treatments both 00 10 colour and a large array of aromas develop. In these reactions amino groups react Swith reducing compounds as a first step and ultimately leading to a whole family of reaction pathways. In foods or feeds the amino compounds involved are predominantly free amino acids which are released from the proteinaceous raw material by various proteases and the required reducing compounds primarily represent reducing sugars.The implication is that during the processsing of the raw material undesired release of free amino acids and sugars should be avoided to minimise off tastes that could be generated during subsequent heating steps as e.g.

during spray drying or sterilisation. The latter notion emphasises once more the benefits of superior purity and low in-use costs of the enzyme according to the invention.

Apart from Maillard reactions, amino acids can also undergo important chemical transitions at ambient temperatures. The latter type of transitions are enzyme dependent and are quite common in fermented foods such as beer, yogurt, cheese ripening and meat and wine maturation processes. In these fermentation processes, free amino acids are liberated from the raw materials used by the proteases added or by proteolytic enzyme activity from the raw material or the microbial starters used.

During the maturation phase microbial metabolic activity then converts the free amino acids into derivatives with increased sensoric properties. For example, L-leucine, Lisoleucine and L-valine lead to the formation of valuable fusel alcohols like amylalcohols and isobutanol in beer fermentation. Similarly cheese volatiles such as methanethiol and dimethyldisulphide have been traced back to the occurrence of methionine in cheese as well as methylpropanoic acid and methylpropanal to valine.

Finally the free amino acid glutamate and can create strong savoury enhancing effects because of its synergy with the breakdown products of RNA, so-called ribonucleotides. If combined with proper concentrations of 5'-ribonucleotides such as 00 O 5'-IMP and 5'-GMP, the detection threshold of the umami taste generated by glutamate N is known to be lowered by almost two orders of magnitude.

In order to obtain pronounced and precise taste effects in all of these processes, the Sproteinaceous substrates should be hydrolysed using a combination of an endo- and an exoprotease, wherein at least one of the endo or exoprotease, preferably both the endo- and exoprotease, are pure and preferably selective towards a specific set of amino acid(s) or preferentially release the preferred amino acid(s). So preferred proteases are characterised by a high selectivity towards the amino acid sequences S that can be cleaved which notion makes the enzyme category in Aspergillus known as "maturases" of particular importance.

Apart from the food and feed industries, proteases are also commonly applied by the chemical, pharmaceutical, diagnostic and personal care industries.

In the personal care industry proteases are used to create peptides which are added to a variety of products to improve aspects like skin feel, gloss or protection. Moreover there is a new tendency towards direct topical application of the protease. Very similar to the enzyme use in the leather industry, the prime aim in the latter application is to clean, dehair and soften the skin In the chemical and pharmaceutical industry proteases are being developed as valuable tools in producing costly ingredients or intermediates. In these industries proteases are not only used because of their hydrolytic capacity but also because of their capacity to synthesise peptides from natural or non-natural amino acids. The latter option is clearly demonstrated by the possibility to synthesize aspartame from its amino acid based building blocks by using'an endoprotease like thermolysin.

Unlike the situation in the food and feed industry, the stereo- and regioselectivity of proteases are also considered important assets although unusual reaction conditions may be needed to accomplish the desired chemical transformation. Typical examples of the application of proteases in this industry include the use of endoproteases, aminopeptidases as well as carboxypeptidases in the production of various intermediates for drugs like insulin, antibiotics, renin and ACE-inhibitors An overview of such uses is presented in Industrial Biotransformations, A.Liese, K. Seelbach, C.

Wandrey, Wiley-VCH; ISBN 3-527-30094-5.

In view of the desired specificities, stereo- and regioselectivities, the absence of side activities and resistance to unusual reaction conditions such as high solvent 00 O concentrations, the improved performance of the protease according to the invention

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offers substantial advantages.

SFrom a pharmaceutical point of view the role of proteases is illustrated by a substantial number of references in Martindale's, "The Extra Pharmacopoeia" (Pharmaceutical Press, London, UK). Moreover the important role of very specific proteases in V' regulating all kinds of biological processes is illustrated by the fact that many hormones become active only after the processing of an, mostly inactive, precursor molecule by such a very specific protease. Inhibitors active towards certain categories of such 0 10 specific proteases have been implicated in the development of all kinds of new drugs.

O Therefore new and effective inhibitors for protease may now be identified using the sequences provided herein.

The entire disclosure of each document cited herein is hereby incorporated by reference Table 1 SEQ ID number Function of encoded protein EC number Gene cDNA Protein 1 58 115 Pepsin A 3 EC3.4.23.1 2 59 116 Metalloprotease EC3.4.24.56 3 60 11l 7 acylaminoacyl-peptidase EC3.4.19.1 4 61 118 Tripeptidylaminopeptidase E03.4.14.- 62 119 serine carboxypeptidase EC3.4.16.6 6 63 120 Serine endoprotease EC3.4.21.

7 64 121 Carboxypeptidase Y EC3.4.1 8 65 122 aspergillopepsin 11 horn EC3.4.23.19 9 66 123 Tripeptidyl peptidase EC3.4.14.9 67 124 Tripeptidyl peptidase EC3.4.14.9 11 68 125 aspergiIlopepsln 11 horn EC3.4.23.19 12 69 126 Tripeptidyl peptidase EC3.4.14.9 13 70 127 Metalloprotease EC3.4.24.- 14 71 128 aspergillopepsin I EC3.4.23.18 72 129 Pepsinogen E EC3.4.23.25 16 73. 130 aspergillopepsin I horn EC3.4.23.18 17 74 131 aspergillopepsin 11 EC3.4.23.19 18 75 132 Pyro-Glu peptidase EC3.4.19.3 19 76 133 dipeptidyl peptidase EC3.4.14.2 77 134 Secr. arninopeptidase EC3.4.1 1.10 21 78 135 alkaline D-peptidase EC3.4.16.4 22 79 136 Carboxypeptidase EC3.4.16.1 23 80 137 Carboxypeptidase EC3.4.1 6.1 24 81 138 Carboxypeptidase-lI EC3.4.16.1 182 139 aspartic proteinase EC3.4.23.- 26 83 140 Tripeptidyl peptidase E03.4.14.9 27 84 141 Carboxypeptidase EC3.4.16.1 28 85 142 cysteine proteinase EC3.4.22.- 29 86 143 Metallocarboxypeptidase -IEC3.4.1 7.- SEQ ID number Function of encoded protein EC number Gene cDNA- Protein 87 1T4 Subtilisin horn. E03.4.21.62 31 88 145 Carboxypeptidase Y EC3.4.16.5 32 89 146 Metalloprotease EC3.4.24.- 33 90 147 Carboxypeptidase Y EC3.4.16.5 34 91 1 48 Metalloprotease EC3.4.24.- 92 149 Tripeptidyl peptidase EC3.4.14.9 36 93 150 Aspartic protease EC3.4.23.24 37 94 1f51 Aspartic protease EC3.4.23.24 38 95 152 Pepsin A 3 EC3.4.23.1 39 96 153 Aspartic protease EC3.4.23.24 97 154 Aspartic protease EC3.4.23.24 41 98 155 Kex EC3.4.21 .61 42 99 156 Serine protease EC3.4.21.- 43 100 157 Glutamyl endoprotease EC3.4.21.82 44 101 158 aspergillopepsin 11 horn EC3.4.23.19 102 159 acylaminoacyl-peptidase EC3.4.1 9.1 46 103 160 Tripeptidylaminopeptidase EC3.4.14.- 47 104 161 serine carboxypeptidase EC3.4.1 6.6 48 105 162 GIy-X carboxypeptidase EC3.4.17.4 49 106 163 aspartic proteinase EC3.4.23.- 107 164 Tripeptidyl peptidase EC3.4.14.9 51 108 165 Carboxypeptidase-I EC3.4.16.1 52 109 166 serine carboxypeptidase EC3.4.16.6 53 110 167 serine carboxypeptidase EC3.4.1 6.6 54 111 168 Secr. amninopeptidase EC3.4.1 1.10 112 169 Prolyl endopeptidase EC3.4.21.26 56 113 170 aspergillopepsin I horn EC3.4.23.18 57 114 171 Amninopeptidase EC 3.4.11l.- 00 8 EXAMPLES SExample 1 Assaying Proteolytic Activity and Specificity Protease specificity may be explored by using various peptide substrates. Synthetic n substrates are widely used to detect proteolytic enzymes in screening, in fermentation, C during isolation, to assay enzyme activity, to determine enzyme concentrations, to C investigate specificity and to explore interaction with inhibitors. Peptide p-nitroanilides 00 are preferably used to assay protease activity as the activity can be followed Scontinuously and therefore allow for kinetic measurement. The cleavage of peptide pnitroanilides can be followed by measuring the increase in adsorption at 410nm upon release of the 4-nitroanilide. Paranitroanilide substrates are generally used for serine and cysteine proteases. In addition peptide thioesters and 7-amino-p-methylcoumarin peptide derivates are used. Peptide thioesters are very sensitive substrates for serine and metalloproteases that exhibit relatively high turnover rate since the thioesterbond is easier to cleave than the amide bond. Cleavage of thiolesters may be followed with a thiol reagent such 4,4-dithiopyridine (324nm) or 5,5-dithiobis 2-nitrobenzoic acid (405nm). The same increased turnover rate is usually observed for the cleavage of ester bonds relative to amide bond. The most well known substrates to assay the esterase activity of proteases are p-nitrophenol derivates. The release of p-nitrophenol can be monitored at different wavelength dependent on the pH that is used, eg around neutral pH a wavelength of 340nm is used while above pH 9 monitoring is done around 405nm. In addition the hydrolysis of esterS'can also be followed by titration using pHstat equipment. In case of qualitative measurement of esterase activity pH sensitive dyes can be applied.

As an alternative, peptides may be attached to a fluorescent leaving group. Proteolysis is accompanied by an increase in fluorescence when monitored at the appropriate wavelengths. Peptidyl 2-naphtylamides and peptidyl 4-methyl-7-coumarylamides are commonly used. The release of for example 7-amino-4 methylcoumarin is measured using an excitation wavelength of 350nm and an emission wavelength of 460nm. The use of 7-amino-4 trifluoromethylcoumarin has the advantage of the leaving group being both chromogenic (absorbtion 380nm) as well as flourogenic (excitation 400nm, emission 505nm). When it is essential that at both sides of the scissile bond an amino 00 acid is present, the introduction of a group that quenches the fluorescence might be

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useful. The general characteristics of such substrates is that the peptide sequence Sseparates a fluorescent donor group from an acceptor group that acts as a quencher of Sof fluorescence. Cleavage of a peptide bond between the quenching group and the fluorophore will lead to substantial increase in fluorescence. Several donor-acceptor pairs have been reported, including o-aminobenzoic acid (Abz) as the donor and 2, 4 n dinitrophenyl (Dnp) as the acceptor, 5-[(2'aminoethyl)-amino]naphtalenesulfonic acid N (EDANS) as the donor and 4-[[4'-(dimethylamino]phenyl]azo]-benzoic acid (DABCYL) C- as the acceptor. The Abz/EDDnp represents a very convenient donor-aceptor pair since after total hydrolysis, the fluorescence increases by a factor 7 to 100 and the Sabsorption spectrum of EDDnp does not change with pH. Moreover, the peptide sequence may contain up to 10 residues without loss of the quenching effect. As the size of the connecting peptides increases, the position of the scissile bond may become less specific. Therefore in addition to establishing whether proteolysis occurred, additional analysis of the products may be required. This may be done by analysing and separating the produced peptides by HPLC and determining the the amino acid sequence of the fragments. In addition the peptide composition of the digest may be directly analysed by using combined HPLC mass-spectroscopy technique.

Apart from using peptides of a defined sequence also synthetic peptide libraries can be used to study protease specificity. Peptides are synthesised by solid phase synthesis in random or semi-random fashion. E.g. Meldal et al. (PNAS USA 91,3314,1994) report the preparation of a family of protease substrates by starting with H-Lys(Abz)-resin, extending the resin with peptides to a length of six aminoacids, and finally coupling Tyr(N02) to the peptides. Each resin bead has a unique sequence and on treatment with the proteases the most susceptible becomes fluorescent as the Tyr(N02) containing peptide is released. Sequence analysis of the peptides on the susceptible will give information on the specificity of the protease.

Protease activity is usually expressed in units. Generally the international standard unit (IU) is defined as the amount of enzyme, which under defined conditions transfers one micromole of substrate per minute. Specifically with proteases the IU would relate to the hydrolysis of one micromole peptide bond per minute. However in the case of protease units deviations of the international definition are more rule than exception.

Where with the model peptides, which are cleaved specifically at one bond the 00 O calculation of IU's is strait-forward, for proteinacious substrates where the protease can C cleave at various positions to a various degree many deviating unit definition are used.

SApart from a definition of the unit used, any hydrolysis experiment requires an adequate description of the conditions under which the units are measured. Such conditions comprise e.g. the substrate concentration, the enzyme-substrate ratio, the pH and temperature. Typical assays for determining the specific activity of a proteases comprise a proteinacious substrate such as for example denaturated hemoglobin, N insulin or casein. The polypeptide substrate is digested by a protease at fixed N conditions during a fixed time interval. Undigested and large polypeptides are precipitated with TCA and TCA soluble product is determined by measuring Sabsorbance at 220 or 280nm, or by titrating the soluble peptides with folin reagent, ninhydrin, fluro 2,4, dinitrobenzene/ dansylcloride, TNBS method or fluorescein.

Instead of labeling the product after hydrolysis, also polypeptide substrates may be used which are already labeled by specific dyes or fluorophores such as for example fluorescein. In addition standard methods of amino acid analysis may be applied using standard laboratory analyzers. In order to hget insight in the size distribution of the peptides generated by a protease, gel chromatography experiments may be performed. In addition to this HPLC using reverse phase techniques is applied in order to get better resolution of the peptide patterns generated by the protease.

The course of the hydrolysis of proteinacious substrates is usually expressed in the degree of hydrolysis or DH. In case pH-stat is used to follow the course of hydrolysis, DH can be derived from the base consumption during hydrolysis (Enzymatic Hydrolysis of Food Protein, J. Adler-Nissen, 1986, Elsevier Apllied Science Publishers LTD). The DH is related to various useful functional properties of the hydrolysate such as solubility, emulsifying capacity, foaming and foam stability, whipping expansion, organoleptic quality. In addition taste is an important aspect of food grade hydrolysates.

Bitterness can be a major problem in protein hydrolysates. Termination of the hydrolysis reaction may be done by changing the pH, heat inactivation, denaruring agents such as SDS, acetonitril etc.

Polypeptides shown in Tabel 1 were expressed and at least partially purified according to standard procedures known in the art. They were analysed according to al least one of the methods described above and found to have the activities listed in Table 1.

Example 2 0 00 O Direct determination of the kcat/Kmratio for protease substrates.

c Synthetic substrates can be used to monitor the enzymatic activity during purification, to determine enzyme concentration, to determine inhibition constants or to investigate Sthe substrate specificity. Determination of the kcat/Km ratio gives a measurement of the substrate specificity. It allows to compare the specificity of different substrates for a same enzyme or the comparison of hydrolysis rates with different enzymes cleaving V) the same substrate. This ratio has a unit of a second order rate constant and is then Cexpressed as 1/(concentration.time). Substrates having a kcat/Km ratio in the range S10.5-10.6 M-1.sec-1 are considered to be very good substrates i.e good affinity and 00 rapid turn-over. However, some substrates may be very specific with kcat/Km values in Sthe 10.4 M-1.sec-1 range.

The kcat/Km ratio may be calculated after determination of individual parameters. In that case, Km and Vm may be obtained from various linear plots (e.g Hanes or Cornish-Bowden method) or by a non-linear regression method. Knowing that Vm=kcat. Et (where Et is the final active enzyme concentration then kcat= Vm/Et.

Determination of the kcat/Km ratio by the previous method may be prevented when product or substrate inhibition occur, or when substrate precipitates at high concentration. It is however possible to obtain an accurate value of the kcat/Km ratio working under first-order conditions i.e at a substrate concentration far below the estimated Km. In these conditions, the Michaelis-Menten equation: v= (Vm.S)/(Km S) becomes: v=(Vm.S)/Km since S<<Km or v (Vm/Km).S kobs. S -dS/dt which integrates as InS= -kobs.t InSo where So is the starting substrate concentration and S the substrate concentration at a given time. The velocity is proportionnal to the substrate concentration. In other words, the substrate hydrolysis obeys a first order process with kobs as the first-order rate constant. kobs=Vm/Km= (kcat.Et)/Km since Vm=kcat.Et A continuously recording of the substrate hydrolysis will allow the graphical determination of kobs from the InS vs time graph. The kcat/Kr ratio is simply inferred from kobs providing the active enzyme concentration is known: kcat/Km=kobs/Et Assay method: Use a starting substrate concentration far below the estimated Km and a low enzyme concentration to allow the substrate hydrolysis to be recorded. You will obtain a first-order curve for the product generation: After total hydrolysis of the substrate, the absorbance (or fluorescence units) of the 00 product will allow the accurate determination of So, since Pt=So. kobs is determined from the slope of the InS vs time graph or alternatively using a fitting software S(Enzfitter, SigmaPlot...).

NB: Do not forget to calculate the substrate concentration for any given time from the product concentration (S=So-P) since plotting P vs time would not provide the correct kobs (dP/dt=kobs.S does not integrate in the same way).

V Alternatively, one can measure successive 11/2 (half-time) from the product apparition NC curve since in a first order process: N t1/2 In2/kobs=0.693/kobs then kobs= 0.693/tl/2 00 Using this method allows to check that you have a true first order decay (identical C values for the successive t11/2).

Example 3 Inactivating protease genes in Aspergillus The most conveniant way of inactivating protease genes in the genome of Aspergillus is the technique of gene replacement (also called "one step gene disruption"). The basics of this technique have been described-by Rothstein RJ in Meth. Enzymol. 101, p202, 1983. Essentially the technique is based on homologous recombination of transformed DNA fragments with the genomic DNA of a fungal cell. Via double crossover the gene to be inactivated is (partly) replaced by the DNA fragment with which the cell is transformed. Preverably the transformed DNA fragment contains a selectable marker gene for Aspergillus niger. Basically the manipulation of DNA and generation of a inactivation construct are done using general molecular biological techniques. First, genomic DNA is isolated from the Aspergillus niger strain that is later on used for the inactivation of the protease gene. Genomic DNA of A. niger can be isolated by any of the techniques described, e.g. by the method described by de Graaff et al. (1988) Curr. Genet. 13, 315-321, and known to the person skilled in the art. This genomic DNA is used as template for amplification of the flanking regions of the protease gene by using the polymerase chain reaction (PCR; Sambrook et al. (1989) Molecular cloning, a laboratory manual, 2nd edition, Cold Spring Harbor Laboratory Press, New York). With flanking regions is meant here the non-coding regions upstream and downstream of the protease gene that will be inactivated. Preferably the flanking regions should each be more than 1.0 kb in length.

Two single stranded DNA oligonucleotides are used for the priming of the PCR amplification of each flanking region. For the 5'-flanking region, one primer is homologous to a DNA sequence upstream of the start of the coding sequence of the I 1 0 00 O protease gene. Preferably the homologous region is located more than 1.0 kb C upstream of the translation start site. The second primer is homologous to the §complementary and inverse DNA sequence located immediately upstream of the coding sequence of the protease gene.

For the 3'-flanking region, one primer is homologous to the DNA sequence immediately downstream of the coding sequence of the protease gene. The second primer is Shomologous to a complementary and inverse DNA sequence located preferably more Sthan 1.0 kb downstream of the coding sequence of the protease gene.

SThe DNA sequence included in all primers and homologous to the A. niger genome 0 0 10 shou d be minimally 15 nucleotides in length, preferably more than 18 nucleotides in Olength. Most conveniently, all primers should contain a DNA sequence coding for the recognition site of suitable restriction enzymes upstream of the sequence that is homologous to the A. niger genome. These extra recognition sites facilitate the cloning process.

Both primers and the genomic DNA of A. niger are used in a PCR reaction under conditions known to those skilled in the art. The annealing temperature of the primers can be calculated from the part of the DNA sequence that is homologous to the A.

niger genome. Both fragments containing the 5'-flanking region and the 3'-flanking region are cloned into a vector that can be propagated in E. coli using general molecular biological techniques. A gene that can be used as selection marker in Aspergillus niger is then cloned in between the two flanking regions. Most conveniantly the marker gene is under control of a promoter that comes to expression in A. niger, preferably an endogenous A. niger promoter. The orientation of the insertion of the marker gene is preferably in the same direction as the original protease gene. The final inactivation fragment contains the 5'-flanking region, a selection marker gene preferably under control of a A. niger endogenous promoter, and the 3'-flanking region, all in this direction and orientation. DNA of the final construct is cloned into a vector that can be propagated in E. coli.

The inactivation construct is digested with suitable restriction enzymes to remove the E. coli vector sequences and the inactivation fragment is isolated using standard techniques (Sambrook et al. (1989) Molecular cloning, a laboratory manual, 2nd edition, Cold Spring Harbor Laboratory Press, New York). Finally Aspergillu.s niger is transformed with the inactivation fragment using a method described in literature, e.g.

by the method described by Kusters-van Someren et al. (1991) Curr. Genet. 20, 293- 299. Transformed cells are selected by plating the transformation mixture on agar plates that are selective for growth of Aspergillus niger strains that do express the 00 O marker gene. After purification of the transformed Aspergillus strains by replica plating,

C

a representative number of strains is analysed by Southern blotting using standard Smethods (Sambrook et al. (1989) Molecular cloning, a laboratory manual, 2nd edition, SCold Spring Harbor Laboratory Press, New York). Therefore, genomic DNA of mycelium of transformed strains is isolated and digested with suitable restriction enzymes. Restriction fragments are separated using agarose gelelectrophoresis, Sblotted to nitrocellulose membranes and probed with a labeled fragment of the marker Cr gene. Hybridization and washing is under stringent conditions. Strains that contain C labeled restriction fragments of the correct length are considered correct.

00 Using this method A. niger strains can be selected with an inactivated protease gene of choice.

Example 4 Isolating proteases by ion exchange chromatography Small quanties of the protease encoded by the nucleotide sequence as provided herein are obtained by constructing an expression plasmid containing the relevant DNA sequence, transforming an A.niger strain with this plasmid and growing the A.

niger strain in a suitable medium. After collecting the broth free of contaminating cells, the protease sought can be purified.

To isolate the protease as encoded by the provided nucleotide sequence in an essentially pure form several strategies can be followed. All of these strategies have been adequately described in the relevant scientific literature see for example the Protein Purification Handbook ,18-1132-29 Edition AA as published by Amersham Pharmacia Biotech, Uppsala, Sweden). A'procedure which is applicable to purify proteases from complex mixtures is provided hereunder. Essential is that a suitable assay is available that is selective towards the enzyme characteristics sought. For proteases typically a chromogenic, synthetic peptide substrate is used as described in Example 1. Such peptide substrates can be selective towards endoproteases, carboxypeptidases, aminopeptidases or omegapeptidases. In Example 11 the selectivity towards a specific tripeptidylpeptidase is described. By choosing the right amino acid residues in the relevant synthetic peptide, proteases with the desired specificity can be selected.

First it should be determined whether the protease is excreted into the medium, depending on the expression system chosen to produce the protease, it may be excreted or contained in the cell. If the protease is excreted into the fermentation I I V A 00 O medium, the producing cells or fragments of these cells have to be removed by N centrifugation or filtration and the resulting clear or clarified medium is the starting point ;for further purification. In those cases in which the protease sought is not excreted, the Sproducing cells have to be disrupted to enable purification of the protease. In such cases the collected cell mass is best ground with an abrasive, milled with beads, ultrasonicated or subjected to a French press or a Manton-Gaulin homogeniser and then filtered or centrifuged. In case the protease is hydrophobic or membrane bound, the addition of a non-ionic detergent to solubilise the protease before the filtering or centrifugation step may be necessary.

00 After the clarification step, a three phase purification strategy can be applied to obtain Sthe unknown proteases in an essentially pure state. In all or some of these three phases addition of a detergent may be necessary.

In the first or capture phase the target protease is isolated, partly purified and concentrated. During the subsequent intermediate purification phase most of the bulk impurities are removed and in the final polishing phase trace amounts of remaining impurities of larger amounts of closely related substances are removed and the enzyme is dissolved in the desired buffer. Depending upon the nature and physical properties of the protease at hand, a person skilled in the art is capable of optimising the three phases using slightly modified versions of the different protein binding materials and apply these under somewhat changed conditions. However, in all cases a selective analytical assay is indispensible as it will enable the continuous monotoring of the increasingly purified proteolytic activity. Analytical assays suitable for the purpose include the use of chromogenic peptide substrates as has been mentioned before.

In the first capturing phase of the purification a strong ion exchange resin of the anionic type is preferably used to apply the clarified and desalted enzyme containing medium.

To guarantee binding of the desired proteolytic activity to the resin, three or four different pH values of medium and resin are tested under low conductivity conditions.

In these tests the resin is always equilibrated with a buffer of the same pH value and conductivity as the enzyme containing medium. The medium is then applied to the column under pH conditions which has been shown to allow adequate binding of the protease to the resin i.e. none of the desired enzymatic activity can be traced back in the run-through medium. Subsequently the desired enzymatic activity is eluted from the ion exchange resin using a continuous salt gradient which starts with the resin equilibration buffer and ends with this buffer to which 1 mol/liter of NaCI has been added. Eluted fractions containing the desired activity according to the assay are I I I 00 0 pooled and then prepared for an additional purification step. This additional purification C step depends on the purity of the desired enzyme in the pooled fraction if almost pure, an additional gel filtration step will proof to be adequate; if not almost pure, chromatography over a hydrophobic interaction resin is applied followed by a gel filtration step.

Chromatography over a hydrophobic interaction resin is carried out by first increasing C the salt content of the pooled fraction obtained from the ion exchange resin to 4mol/liter of NaCI and by removing any precipitate formed. If the resulting clear fraction doesnot 0 0 10 contain the desired activity, this activity is obviously present in the precipitate and and Scan be recovered in an essentially pure state. If the resulting clear fraction still exhibits the desired activity in the assay, then the liquid is applied as such to a phenyl sepharose resin (Pharmacia) equilibrated in this high salt buffer with an identical pH and conductivity. If the desired enzymatic activity binds to the phenyl sepharose resin, the activity is eluted with a continuous gradient of decreasing salt content followed by a salt free wash and, if nesessary, with a chaotropic agent. Like before those fractions from the gradient that exhibit activity in the assay are pooled and finally subjected to a gelfiltration step. If the desired enzymatic activity doesnot bind to the phenyl sepharose resin, many of the contaminants will, so the desired proteolytic activity as present in the void volume of the column requires only an additional ultrafiltration step to obtain the activity in a more concentrated form before applying it to the gelfiltration column. The gelfiltration column doesnot only remove trace contaminations but also brings the enzyme in the buffer which is required by subsequent use.

Although this method is generally applicable for the isolation and purification of proteases according to the invention, a more specific isolation technique is described in Example 4. In that Example the isolation of an Aspergillus protease is described by using immobilised bacitracin, a peptide antibiotic known for its selective interaction with various types of proteases.

Isolating proteases by affinity chromatography An alternative method for purifying small quantities of protease is by affinity chromatography.To obtain the protease in a purified form, a 100 milliliter culture is grown in a well aerated shake flask. After centrifugation to remove any non-soluble matter, the supernatant is applied to a 40 milliliter bacitracin-Sepharose column I ,I 00 O equilibrated with 0.05 mol/litre sodium acetate pH 5.0. Proteases bound to the column are eluted using the acetate buffer supplemented with 1 mol/litre of NaCI and 10% (v/v) isopropanol (J.Appl.Biochem.,1983 pp420-428). Active fractions are collected, dialysed against distilled water and applied on a 20 milliliter bacitracin-Sepharose column, again equilibrated with acetate buffer. As before, elution is carried out using the acetate buffer supplemented with NaCI and isopropanol. Active fractions, i.e. fractions Sdisplaying the activities sought, are collected, dialysed against a 5 millimol/litre acetate yC buffer pH 5.0 and then concentrated by means of ultrafiltration with a Amicon C, membrane. To obtain the protease in an essentially pure state, the concentrated liquid

O

10 is chromatographed over a Superdex 75 column equilibrated with the 0.05 mol/litre Ssodium acetate buffer pH 5.0 and supplemented with 0.5 mol/litre NaCI.

Further experiments carried out with the purified enzyme on PAGE may confirm if the molecular weight is in line with what can be expected on the basis of the available sequence data. Final confirmation can be obtained by carrying out a partial, N-terminal amino acid analysis.

Example 6 Properties of a novel cysteine protease from A. niger.

In this Example Aspergillus gene nr 28 was cloned and overexpressed in A. niger as described before. The enzyme obtained was purified according to procedures described in Example 4 and used to destroy trypsin inhibiting activity from soybeans under various conditions. As reference materials papain and bromelain were used.

Bromelain was obtained from Sigma, papain was obtained from DSM Food Specialties Business Unit Beverage Ingredients, PO Box 1, 2600 MA Delft, the Netherlands..

Trypsin inhibition was measured according to the method of Kakade, Rackis, J.J., McGhee, J.E. and Puski, G. (1974): J. Cereal Chemistry 51: 376-382.

Degradation of the substrate N-benzoyl-L-arghinine-p-hitroaniline to N-benzoyl-Larginine and p-nitroaniline was taken as a measure of trypsin activity. Trypsin was obtained from British Drug Houses Ltd and was derived from cow's pancreas containing more than 0.54 Anson Units per gram of product.

The Kunitz inhibitor for soybeans was also obtained from Sigma.

The trypsin inhibitor was pre-incubated at a concentration of 2 mg/ml with the above mentioned cysteine protease enzymes at pH 3 in 50 mM Na-acetate buffer prior to measuring trypsin inhibition. Enzymes were added at a ratio of enzyme protein to trypsin inhibitor of 1:100 Albumin served as a negative control for the enzymes.

Remaining trypsin activity was measured after incubation during 3 hours at 37 0 C.Results are shown in Table 2.

Table 2 Effects of various cysteine proteases on the enzymatic inactivation of the Kunitz trypsin inhibitor from soybeans.

1 2 3 4 Enzyme tested Remaining TI Remaining TI Remaining TI Remaining TI activity activity after activity after activity after pepsin heat treatment heat treatment treatment at 75CC at Papain 25 55 78 Bromelain 30 62 86 99 A.niger 26 26 28 Albumin 100 100 100 100 (control) TI Trypsin Inhibitor activity Experiments were repeated in the presence of pepsin during the pre-incubation of cysteine proteases with the trypsin inhibitor. Pepsin was added at final concentration of 1.3 mg/ml. Results are shown in column 3.

Another series of experiments were conducted to check for heat stability. The cysteine proteases were incubated at 75 and 90°C during 5 minutes prior to the addition of these enzymes to the pre-incubation with the trypsin inhibitors. Results are shown in columns 4 and These results clearly demonstrate the superior activity of these novel cysteine proteases from Aspergillus niger over currently available cysteine proteases for the inactivation of trypsin inhibitors in animal feed.

Example 7.

Exo-peptidases promoting cheese ripening and cheese taste.

I b 00 O The amino-peptidases encoded by genes nr 20 and 54 (see Table 1) were C overexpressed in A.niger according to methods described earlier. Purification of these Senzymes was carried out according to procedures as described in Example 4. The activity of the purified enzyme samples was determined at pH7.2 in an aqueous phosphate buffer (50 mM) containing the para-nitro anilide derivative of a number of hydrophobic amino acids (3 mM) as the substrate. The conversion of the substate by the amino peptidase was determined by monitoring the change in optical density at 400 Snm as a result of substrate conversion, using a solution not contaning the enzyme as the reference. Activity was calculated as the change in OD per minute and expressed as e.g. Phe-AP, Leu-AP or Val-AP units, depending on the substrate used.

SNormal cheese milk was inoculated with starter culture of the Delvo-tec TM DX 31 range (DSM Food Specialities Delft, The Netherlands) to obtain a Gouda-type cheese and coagulating was executed with an average dosis of coagulant (50 IMCU per liter of cheese milk). In addition, 25 Phe-units of each exo-protease was added to two experimental cheeses whereas the control did not contain either one of the exoproteases. Cheese making parameters were used conform the procedure applied for semi-hard cheese for both cheeses. A difference was noted in terms of flavor and aroma development between the experimental cheeses and control cheese to such an extent that the experimental cheeses has obtained most of its organoleptical properties after three weeks whereas the control cheese has obtained a similar qualification after six weeks. The level of free amino acids after three weeks was shown to be twice as high in the experimental cheeses; after six weeks of ripening the levels were comparable again. Amino acid analysis was carried out according to the Picotag method of Waters (Milford MA, USA).

These data suggests that the product is ready for sale three weeks earlier without decreasing the keeping quality of the cheese. The organoleptic character of the experimental cheeses differed from the control to the extent that the bland cheese flavor with a slight tendency to bitterness of the control cheese was overcome in the experimental cheese in the presence of the amino-peptidase. The texture of the cheeses was found to be somewhat smoother as well.

r, f 00 0 Example 8 SNovel specificity of a protease encoded by gene SAs explained earlier, certain proteins can resist enzymatic hydrolysis as the result of specific amino acid compositions or specific tertiary structures. In such cases the quantity of peptides that can be solubilised from protease resistant proteins can be dramatically n improved by using proteases exhibiting novel specificities.

CBeta-casein is a protein with very limited tertiary structure but with an extraordinary high Slevel of proline residues. Many proteases have difficulties in cleaving proline containing sequences so that the hydrolysis of beta-casein with commonly available proteases Syields a hydrolysate that is relatively rich in large, protease-resistant peptides. The latter resistant peptides can attribute to a number of undesirable properties of the hydrolysate.

For example, it is well known that these larger peptides have a relatively strong effect on allergenicity and bitterness. Moreover, these peptides withstand a further degradation into free amino acids so that in certain processes the occurrence of these large, protease resistant peptides are synonymous with yield losses. Therefore, the availability and use of proteases that are capable of cleaving the protease-resistant parts of the proteins, translate into serious technical and economical benefits.

Beta-casein represents one of the major casein fractions of bovine milk. The protein has been well characterised in terms of its amino acid sequence and is commercially available in an almost pure form. As such, beta-casein offers an excellent test substrate for studying the relationship between enzyme cleavage sites and the length of various peptides formed during enzyme hydrolysis.

This Example demonstrates that despite the broad spectrum cleavage character of the endoprotease subtilisin, the addition of a very specific enzyme like a prolyl endopeptidase as encoded by gene 55 (see Table 1) has a major impact on the size of the beta-casein fragments formed..

Beta-casein from bovine milk (lyophilised,essentially salt-free powder) with a minimum beta-casein was obtained from Sigma. Subtilisin from B.licheniformis (Delvolase®, 560 000 DU per gram) was obtained from DSM Food Specialities (Seclin, France). The proline-specific endoprotease as encoded by gene 55 was overexpressed in A. niger and purified using procedures described in Example 4.

Beta-casein powder was dissolved at a concentration of 10% together with 0.1%

I

00 O Delvolase T M powder in a 0.1 mol/liter phosphate buffer pH7.0. After an incubation

C

of 24 hours at 450C in a shaking waterbath, the reaction was stopped by heating the Ssolution for 15 minutes at 90 0 C. To one half of the solution (iml containing S100milligrams of beta-casein) 100 microliter of the proline-specific protease was added and the reaction was continued for another 24 hours at 45°C. After another heat shock at 900C, samples of both the DelvolaseTM and the DelvolaseTM proline-specific n endoprotease treated beta-casein material were analysed by LC/MS equipment to

N

C study the precise peptide size distributions in the two samples.

00 LC/MS Analysis rC HPLC using an ion trap mass spectrometer (ThermoquestTM, Breda, the Netherlands) coupled to a P4000 pump (Thermoquest", Breda, the Netherlands) was used in characterising the enzymatic protein hydrolysates produced by the inventive enzyme mixture. The peptides formed were separated using a PEPMAP C18 300A (MIC-15-03- C18-PM, LC Packings, Amsterdam, The Netherlands) column in combination with a gradient of 0.1% formic acid in Milli Q water (Millipore, Bedford, MA, USA; Solution A) and 0.1% formic acid in acetonitrile (Solution B) for elution. The gradient started at 100% of Solution A and increased to 70% of solution B in 45 minutes and was kept at the latter ratio for another 5 minutes. The injection volume used was 50 microliters, the flow rate was 50 microliter per minute and the column temperature was maintained at The protein concentration of the injected sample was approx. micrograms/milliliter.

Detailed information on the individual peptides was obtained by using the "scan dependent" MS/MS algorithm which is a characteristic algorithm for an ion trap mass spectrometer. Full scan analysis was followed by zoom scan analysis for the determination of the charge state of the most intense ion in the full scan mass range.

Subsequent MS/MS analysis of the latter ion resulted in partial peptide sequence information, which could be used for database searching using the SEQUEST application from Xcalibur Bioworks (ThermoquestM, Breda, The Netherlands).

Databanks used were extracted from the OWL.fasta databank, available at the NCBI (National Centre for Biotechnology informatics), containing the proteins of interest for the application used.

By using this technique as a screening method only peptides with a mass ranging from approx. 400 to 2000 Daltons were considered suitable for further analysis by MS 4 A 00 O sequencing.

C1 Angiotensin (M=1295.6) was used to tune for optimal sensitivity in MS mode and for optimal fragmentation in MS/MS mode, performing constant infusion of 60 gg/ml, Sresulting in mainly doubly and triply charged species in MS mode, and an optimal collision energy of about 35 in MS/MS mode.

In the sample digested with Delvolase alone, the LC/MS/MS analysis identified iG peptides covering various parts of the beta-casein molecule. Together these peptides S accounted for 79% of the total beta-casein sequence. Different retention times of the 0 10 peptides on the C18 column could be traced back to peptide lengths ranging from 2 to S23 amino acid-residues. Together 15% of the peptides found were smaller than 6 amino acids. The sample digested with Delvolase T and the proline-specificprotease also generated a large number ofl identifiable peptides from beta-casein. Together these peptides covered 50% of the total beta-casein protein sequence. In this sample thepeptide size distribution was remarkably homogeneous, as the peptides ranged in length only between 2 and 6 residues. The results show that in the hydrolysate made with the proline-specific protease contain a large fraction of di-, tri-, up to 6 AA peptides, showing the distinct beneficial effect of the co-incubation with an endoprotease featuring an unusual specificity.. It is also clear from these experiments that the endoprotease according to gene 55 encodes an endoprotease that cleaves the peptide chain at the carboxyterminus of the proline residue.

Example 9 The selective release of specic amino acids to promote flavour formation.

Free amino acids like leucine and phenylalanine have not only been implicated in Maillard reactions but also as precursor for desirable aromas in various food fermentations. To promote the formation of such aromas in food fermentations or during the heating, roasting or baking phase of food, it would be advantageous to incorporate into these products a protein hydrolysate that contains relatively high levels of these specific amino acids in a free form.In this Example we describe the production of yeast extracts selectively enriched t in leucine and phenylalanine. This enrichment is obtained by combining an endoprotease with a cleavage preference for a selected set of amino acid residues with an exoprotease favouring the release of a similar set of amino acid residues. The preference of the endoprotease should match with the preference of the exoprotease used. For example we have established that the 00 O aminopeptidases encoded by genes 20 and 54 (see Tablel) feature a definite s preference for releasing leucine and phenylalanine residues which matches with the cleavage preferences of thermolysin. The carboxypeptidases encoded by genes 23 and 24 have a preference for releasing arginine and lysine residues which matches the cleavage preferences of trypsin. Carboxypeptidase encoded by gene 5 features a highly unusual preference for releasing glycine which could be combined with certain i' endoproteases present in papaine.The carboxypeptidase encoded by gene 51 is capable of removing glutamate residues which matches the glutamate specific i protease encoded by gene 43.

The endoprotease thermolysin (commercially available as Thermoase)C 180 from Daiwa Kasei KK (Osaka, Japan) is known to cleave peptide bonds at the amino terminal side of bulky, hydrophobic amino acids like Leu and Phe. To liberate the thus exposed amino acids from the newly formed peptides, we used the amino-peptidases encoded by genes nr 20 and 54 (see Table These genes were overexpressed in A.niger according to methods described earlier and purification of these enzymes was carried out according to procedures as described in Example 4.

To release as much leucine and phenylalanine as possible without concomitant release of undesired amino acids with this combination of enzymes, it is evident that the conditions used during enzymatic hydrolysis should be carefully selected. Moreover, the yeasts own endogeneous (and probably aspecific) proteases have to be inactivated. After a number of test incubations, a protocol was worked out that leads to a surprisingly selective and effective release of leucine and phenylalanine from the yeast proteins using these two new enzymes.

To inactivate the yeasts endogeneous proteases, the yeast suspension was kept for minutes at 95 degrees C. Then the suspension was quickly cooled down to the required temperature and the pH was adjusted to 7.0 using 4N NaOH.The yeast, the thermolysin and one of the aminopeptidases were all incubated simultaneously under the following conditions. After the heat shock, the pH of the 2000 milliliters yeast suspension was adjusted to 7.0 after which 680 milligrams of Thermoase were. added and, after stirring, the purified aminopeptidase. The mixture was incubated with stirring at 50 degrees C for 3 hours and centrifuged. To stop all enzymatic activities the pH of the supernatant was adjusted to 4 and subjected to another heat treatment of minutes at 95 degrees C. After another centrifugation a sample for amino acid analysis was obtained from the supernatant. Precipitated or non-dissolved matter was removed by centrifugation for 15 minutes at 3500 rpm in an Hereaus Megafuge 2.0 R a 00 O centrifuge. Supernatant was removed and kept frozen at 200C.

C Samples of the supernatant, were analysed for amino acid content according to the Picotag method of Waters (Milford MA, USA) immediately after thawing.

In the amino acid analysis Trp and Cys values were omitted And Asp and Asn values were summed as one value. According to the data obtained, in the resulting i' hydrolysate the ratio between alanine and leucine (21.3: 11.7) was 1: yC Commercially available yeast hydrolysates typically exhibit alanine versus leucine ratio's of 1: 0.3 00 In a second experiment a yeast extract was prepared that was enriched in free glutamate. To achieve this, use was made of an endoprotease exhibiting a preference for cleaving at the C-terminal end of glutamate residues (encoded by gene nr 43 in Table 1) and a carboxypeptidase encoded by gene nr 51 in Table 1) capable of removing these glutamate residues thus exposed. The endoprotease encoded by gene nr 43 and the carboxypeptidase encoded by gene 51 (see Table 1) were overexpressed in A.niger according to methods described earlier. Purification of these enzymes was carried out according to procedures as described in Example 4.

The essential role of free glutamate in a number of aroma forming processes is well documented and MSG, the sodium salt of glutamic acid, is recognized as the single most important taste enhancing component.

In this Example the pH of the 200 ml heat shocked yeast suspension is adjusted to then the purified enzyme product encoded by gene 43 is added and the mixture was incubated for 4 hours at 50 degrees C. Then the pH was lowered to 5.0 and the suspension was centrifuged. To 100milliliters of supernatant the purified gene product of gene 51 is added. Incubation with this carboxypeptidase took place for 30 minutes at degrees C with continuous pH adjustments. After stopping the enzyme incubation by a heat treatment of 5 minutes by 95 degrees C, the material was again centrifuged (see above) and a sample was obtained for amino acid analysis.

According to the amino acid data obtained (see above), in the resulting hydrolysate the ratio between_alanine and glutamate (30.0 48.7) was 1: 1.6. Commercially available yeast hydrolysates typically exhibit alanine versus glutamate ratio's of 1: 1.

00 0 Example C1 Flavour evaluation of yeast hydrolysates enriched in specific amino acids.

To prove that a protein hydrolysate enriched in specific amino acids according to the invention can generate specific aroma's, a number of experiments were carried out with the yeast hydrolysates described in an earlier Example. To that end larger portions of these hydrolysates were prepared and lyophilised. The performance of the resulting Spowders were compared with the performance of a commercially availble yeast extract (Gistex LS, obtainable from DSM Food Specialties, Delft, The Netherlands) in a Sstandardised mixture under several reaction conditions. The standardised mixture S 10 consisted of one of the hydrolysates, base mixture and water.

SThe base mixture contained 22 grams of Maxarome Plus Powder (a specialised yeast extract with a high content of natural nucleotides,also obtainable from DSM Food Specialties), 29.2 grams of glucose, 9 grams of REFEL-F fat (hydrogenated soy oil, obtainable from Barentz, Hoofddorp, The Netherlands) and 0.2 grams of calcium stearoyl lactylate emulsifyer, obtainable from Abitec, Northampton, UK) thoroughly mixed in a mortar.

All standardised mixtures contained 5 grams of yeast hydrolysate powder i.e. either the leucine or the glumate enriched material or the commercial yeast extract) 3 grams of the base mixture and 3 grams of water. After thorough mixing, these three slurries were subjected to different heating regimes i.e. either 65 minutes at 90-95 degrees C in a reaction vial (liquid reaction)or dried at 20 millibar at 120 degrees C in a vacuum oven (vacuum roast reaction) or heated in an open reaction vial at 120 degrees C for minutes after the dissipation of all water (roast reaction).

After the heat treatment all three products 'had assumed colours ranging from dark brown to almost black. In case of the vacuum roast reaction only the light coloured top layers were used. Taste evaluation of the heated products was carried out by grinding the blackened cakes into fine powders and dissolving these powders to a concentration of 2% in water containing 0.6% NaCI. The observations of the taste panel are specified in Table 3.

Table 3 Reference Leucine Glutamate Liquid Bouillon, slightly Cold tea, slightly flowery, More bouillon, meaty, roast yeasty yeasty Vacuum Burnt, fried potatoes Astringent, beans, yeasty Burnt, bouillon, yeasty roast Roast Dark roast, bouillon, Less roast, flowery, umami Roast, more bouillon, umami more umami Example 11 Non-allergenic whey protein hydrolysates formed with tripeptidylpeptidases.

The dipeptidylpeptidases encoded by the genes 19 and 55 as well as the tripeptidylpeptidases encoded by the genes 4, 9, 10, 12, 26, 35, 46, and 50 (see Table 1) may be overproduced as described and may be purified according to the methods provided in Example 4. After purification the pH optimum and the temperature stability of each individual enzyme may be established by any of the methods available and known by the skilled person. Furthermore, the specificity of each individual enzyme may be determined using the methods outlined in Example 1. The selectivity exhibited by tripeptidylpeptidases is illustrated in the following experiment.

The enzyme encoded by gene 12 was overproduced in an Aspergillus niger host cell and purified by procedures described in Example 4. The enzyme thus obtained was incubated at pH 5 and 50 degrees C with different synthetic chromogenic substrates i.e. Ala-Ala-Phe-pNA and Ala-Phe-pNA (both from Bachem, Switserland). The incubation with the Ala-Ala-Phe-pNA substrate led to a significant increase of the absorbance at 410 nm whereas the incubation with Ala-Phe-pNA did not. This observation clearly demonstrates that tripeptidylpeptidases cleave off tripeptides and do not exhibit aminopeptidase activity that can lead to an undesirable increase of free amino acids.

Moreover, the enzyme encoded by gene 12 shows favourable enzyme stability characteristics as shown in the following experiment. Four samples of the enzyme were incubated at pH 5 for one hour at 0, 40, 50 and 60 degrees C respectively. Then each enzyme sample was incubated with the above mentioned Ala-Ala-Phe-pNA substrate in a citrate buffer at pH5 and the residual activity in each individual sample was .4 '06 94 00 O determined by measuring the increase in absorbance at 410 nm. With the 0 degrees C C sample showing 100% activity, the 40 degrees sample showed 96% residual activity, the 50 degrees sample 92% residual activity and the 60 degrees sample 88% residual activity.

In a typical process aimed at producing a hydrolysate with a high proportion of tripeptides, whey protein (WPC 75) may be dissolved/suspended in a concentration of 100 grams of protein/liter, in an aqueous medium having a pH of 8.5. The first enzyme Sincubation is with the broad spectrum endoprotease subtilisin (Delvolase@, 560 000 DU per gram from DSM). After a predigestion of the whey with this enzyme in a 00 10 concentration of 0.5% enzyme concentrate per gram of protein for 2 hours at Sdegrees C, the mixture is heat-treated to inactivate the endoprotease used. Then the temperature is adjusted to 50 degrees C and the tripeptidylpeptidase is added and the whole mixture is incubated until the desired level of tripeptides is reached. Further processing steps of the hydrolysate thus obtained depend on the specific application but may incorporate microfiltration or centrfugation followed by evaporation and spray drying.

Claims (23)

1. An isolated polynucleotide hybridisable to a polynucleotide according to a ;sequence selected from the group consisting of SEQ ID NO: to SEQ ID NO:57 or a sequence selected from the group consisting of SEQ ID NO:58 to SEQ ID NO:114.

2. An isolated polynucleotide according to claim 1 hybridisable under high Sstringency conditions to a polynucleotide according to a sequence selected from the group consisting of SEQ ID NO:1 to SEQ ID NO:57 or a sequence selected 00 from the group consisting of SEQ ID NO:58 to SEQ ID NO:114. 0 10 3. An isolated polynucleotide according to claim 1 or 2 obtainable from a filamentous fungus.

4. An isolated polynucleotide according to claim 3 obtainable from A. niger. An isolated polynucleotide encoding a polypeptide comprising an amino acid sequence according to a sequence selected from the group consisting of SEQ ID NO:115 to SEQ ID NO:171 or functional equivalents thereof.

6. An isolated polynucleotide encoding at least one functional domain of a polypeptide according to a sequence selected from the group consisting of SEQ ID NO:115 to SEQ ID NO:171 or functional equivalents thereof.

7. An isolated polynucleotide comprising a nucleotide sequence according to a sequence selected from the group consisting of SEQ ID NO:1 to SEQ ID NO:57 or a sequence selected from the group consisting of SEQ NO:58 to SEQ ID NO:114 or functional equivalents thereof.

8. An isolated polynucleotide according to a sequence selected from the group consisting of SEQ ID NO:1 to SEQ ID NO:57 or a sequence selected from the group consisting of SEQ ID NO:58 to SEQ ID NO:114.

9. A vector comprising a polynucleotide sequence according to any one of claims 1 to 8. A vector according to claim 9 wherein said polynucleotide sequence according to any one of claims 1 to 8 is operatively linked with regulatory sequences suitable for expression of said polynucleotide sequence in a suitable host cell.

11. A vector according to claim 10 wherein said suitable host cell is a filamentous fungus. W:MarnaFIL AU PmsV7331U)sio0Div dils 5.0 soc 00 12. A method for manufacturing a polynucleotide according to any one of claims 1 Sto 8 or a vector according to any one of claims 9 to 11 comprising the steps of Sculturing a host cell transformed with said or said vector and isolating said polynucleotide or said vector from said host cell.

13. An isolated polypeptide according to a sequence selected from the group consisting of SEQ ID NO:115 to SEQ ID NO:171 or functional equivalents thereof.

14. An isolated polypeptide according to claim 13 obtainable from Aspergillus niger. (N 15. An isolated polypeptide obtainable by expressing a polynucleotide according to O 10 any one of claims 1 to 8 or a vector according to any one of claims 9 to 11 in an C<N appropriate host cell, e.g. Aspergillus niger.

16. Recombinant protease comprising a functional domain of a protease polypeptide.

17. A method for manufacturing a polypeptide according to any one of claims 13 to 16 comprising the steps of transforming a suitable host cell with an isolated polynucleotide according to any one of claims 1 to 8 or a vector according to any one of claims 9 to 11, culturing said cell under conditions allowing expression of said polynucleotide and optionally purifying the encoded polypeptide from said cell or culture medium.

18. A recombinant host cell comprising a polynucleotide according to any one of claims 1 to 8 or a vector according to any one of claims 9 to 11.

19. A recombinant host cell expressing a polypeptide according to any one of claims 13 to 16. A recombinant host cell comprising a polynucleotide encoding a functionally inactivated protease polypeptide.

21. A recombinant host cell wherein a polynucleotide encoding a protease polypeptide has at least partially been deleted.

22. A recombinant host cell according to any one of claims 18 to 21 wherein said host cell is from an Aspergillus species, e.g. A. niger.

23. A recombinant host cell functionally deficient in a protease obtainable by a method comprising said steps of: a. In vitro mutagenesis of a polynucleotide according to any one of claims 1 to 11; W:VArMaFILESIAU PmS%76331%Diviuinna) W "ms 00 b. Transformation of a host cell comprising an endogenous gene comprising a Spolynucleotide sequence hybridisable to said mutagenised obtained in step a); c. Selecting and isolating recombinant host cells in which said endogenous gene is replaced by a mutagenised polynucleotide obtained in step a).

24. Purified antibodies reactive with a polypeptide according to any one of claims 13 to 16. Fusion protein comprising a polypeptide sequence according to any one of claims 13 to 16. 00 O 10 26. Method for diagnosing whether an organism is infected with Aspergillus (C comprising said steps of: a. Isolating a biological sample from said organism suspected to be infected with Aspergillus; b. Isolating nucleic acid from that sample; c. Determining whether said isolated nucleic acid comprises polynucleotides hybridisable to a according to any one of claims 1 to 8.

27. Method according to claim 26 wherein step c) additionally comprises amplification of said isolated nucleic acid, preferably by polymerase chain reaction.

28. Method for diagnosing whether a certain organism is infected with Aspergillus comprising said steps of: a. Isolating a biological sample from said organism suspected to be infected with Aspergillus; b. Reacting said biological sample with an antibody according to claim 24; c. Determining whether immune complexes are formed.

29. An isolated polynucleotide according to any one of claims 1, 5, 6, 7 or 8 substantially as herein described. An isolated polypeptide according to claim 13 substantially as herein described.

31. A method according to claim 26 or 28 substantially as herein described. W.WamFILESAU Pml770331%Dwijoafrv dam, 5.O8doc SEQUENCE LISTING <110> DSM NV <120> Novel genes encoding novel proteolytic enzymes. <130> 20095W0 <160> 171 <170> Patentln version 3.1 <210>~ 1 <211> 2520 <212> DNA <213> Aspergillus niger <400> 1 cgcaggcgtc cgttgcgccg cgaaaacctg ccgagtgggc cgtttaggct ttgggtctcc ccacgatgta agcataatca ttctgtgcct gagtgtgaat tctcctgttg cttaattctl tccgtgttcz tttcttatac cgt tat cagc ctagcaatct aCtccggcta acatttgtat gacaattgcg ccacagcgtc accatcaaac ctgccagtac gagtccctgt gtggtagcgg atttcataca gacacaggcg atgcacaata agtgtgggct :aaCtgcatg itttccatc tttcttttct act ttatctt atcgtttgat tgaaatatta cacctgatct ataaattcat tcgttacagc tcgatacgtc caaaaccaag cactgaacat aaactccctc tctctgtcgt gctctgatac ccttcggttc atggaactgg aaaagcacttc :cttgctcttc tcacctcgtt ttgctcgtct ctttctagag ttctcaatct ggctgagata tgcttgcacc agcgtgtctt ggacgacatc cgatgctcta caaaaggatt ttggtctaac caacattggg ctgggttttc ggacgattct gtctgtcagc Iggtgctattt ttctttgtgt tcttcctatt cttttatctt cattgtcctg gcctaaaacc ggagagtccg tgttattgat tgcgccagtg tcagcccgtg gcagacgatt cccgttcgtc accgccgctc1 tctgatgagaz ggttccaact g tctttttcct cgacatttac cactctctgt cacttgtttg attgtgtcat aaattct act gcatctcatc tcttccaagt ccacggcttt attcattagc ccacctcatc gtgacaatga :cgatcaaga iatctatgta c ;cacgtccac a gaggctgcat ttctttcttt aaatcacatt gttcagcatt tgjcctttcca tctgtcattg ctatcactac gtctgcatca tatgcatctc cat cccatac tcgtcgtttc tgccagcgat tttcaagatt :ggtagcgac :atgttgctc Iccctgcacg rgaagagtgg ctcacgatt aacttcgag 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 tcgacccttg aaatgacatc ggcttgctag gaaaagacaa gcaaatgtca ctgtacgcat gactttcgga cttgcttcca acgcatcgga tcgtacccaa tggacggcat tctcggtctc ggtcgaacca acgatagttc ctacgacaac 1260 1 282 ccaa cat tc, gccctttca( aagtacacc( cccgtggacc. at cga t accc Ctcattcccc aagctacaac gcaacttcaq atct ggct cc ttacgggtcg tctggaacaa tctgctagct cctcagtatt gcatcttact ttgtatttgc aagtccttct CCctgtctaa CCttgtccgg atcctgagga attgtaccct 3tggatgccgt :gtagccccgc 3 gcgatatcac atgtctatgt Igaacttctta Igcgccaaatc Itggcattctc gttctggatg tgggtgacac gatttgcaga gcagcacctc ctagtagttc tcttctctgc cgacgcctga atatattctt ctaatcaatc gaaaaagttg gatcagtgtg ttcatcctga cccacagcca -tgcagaaagl -caaggatggc *ctacaccgat *tggcggcact tgctatgctc ttcggggagc tggtgtgaat cgtttcgaac gtttctcaaa gcgttcctcg ggqatccact atctgatgct tctggcqatt acctcgggaa cqagcctgga aacatttatt gtatagaaca tat gact tcg tctccttacc tcaggatatc aacgttttcz acggtcagct accgtcggat tcatgcgatt I ccttcaagcg taccacatta tacaccatct attatcagct aatgtqtatg aacaccacct acaacgggca qaatcaggaa gcttccttca a ca ta tgcat cqgcqtqcgq ctt act ccac tggcatccac ggtacgattc tagtatggac gaaatcggcc 1aqtcgaatat ttggcactac cggacagcta tctccaacaa actcqaagac ttccgtgcaa cgccgaagga acgacttatt ctgtgtttga ctgcgtcgaa gctcaacgac gtagcatgac tqctttggct tatttacaca gtcatattac cagttctggc tacctggaac tgacatgaca ttatcaaagt aacagcgact 1 cgttggcttc tgacaaggac ttggcgcatt atcagccatc qctgcacagt cacaactact ctacgtggga tggtgatgac ctacgatgag ctctacgagc tacgacgagc cat tcccgct ctagttaacc tgctgctgat cttacattcg tcgcaattaa attcaaagaa gttagcgtcc .cttqacgct catcacatg 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 gcgaacaccc tcctcaccca tqatactgag gccccagatc cagagccggc cgacgaaaac 2520 <210> 2 <211> 500 <212> DNA <213> Asp <400> 2 taggaaaatc tcagcaccga taagcaagag aagcqccaca agatatacca accgccatgt 1 ergillus niger agaggcgaca atttgctccg atactggata ctggcttatg tcctgctccg ataccttagc cccttggttc ttggtaatcgqgcggatcaaa ctaggctctg cctccctctt acagaagatc aggactccaa tgcagcagat cgcaaccgaa gacttcaccg ctcaccgcct tagctgcgat agtaccatcg ggacattatg aacgtaaaga tgccaqgtat agggaaggcg gggcaagacc gtcacgaaat ttagtagttc agacaaacag cgatccacaa agctgtcaac acgaacgatc 120 180 240 300 360 2 /282 tcgctcttcc ccagggccaq actgaggccq attatatgat ttttttcttt cttttccgtg tgtctcgtc acacgggtt ct gaact cc tgacctcaa agttactat taccagccc ttttctgta tgcctccat ccttgttcti cgcaccctqi t tcctaaaac ggggtgtgat catet act cF gcgagtttqc aagqacccaa Ctcctcacac tccttgacaa acacggccta acctaqagca atattgatgq ataactctgc gttttcgcta tccgagcgtt aagtagatca tcattcccag cat tggagaa agatagaaat Ctgtcctcat t gctgctata g tttttttgt a Ctctgaacc a attcctgaa t gagaagcct t gaactccat t taaacatcc, 3 cagcatgctl -gctattggti a acctcaagc Itttgcgcttc cacaggattt iaaagagccat tcagtatgag agtcacaggt gttggagcac gctagcaaca caccttggac tgttatagct cgctggagac agaqttaatc cgagacaggc ccatcgtgag ccagaacatg tcctqattca qtccattgtc tagattcctc ttcgaagata t tcttatttt g aattatctg g ttacagttq a catcataat 9 attcggqca t gaataaaaa El atcctcaac, -cgtggtctti a tttcaaacal IttgCtagctl tggcctatgc ggttctaaat ttcaagctac itcggagagaa tattttgttc ttgtgcttta cgtqtttatt acagcaggct ccaacactga gacgctggag gatctaaccg qqtatqatgg atgtaccagc ctggagacct cctttcaaga cagactgtgg ctgttcggta aagatacctc t tggtgtggtg g agggtaacct c ggcqtcaagc a acgcttctcg a aaagcaagaa cggcagcctta gtgatgtcqt ggaatgggtg ctctaaaatg attactaaca cacatttcca tccaqaagtt caggcatqag tagccacaga tgggctcgcg cgaqcaccaa gggaaqggtt caqatgaaqg tcgtctactc g ctcgtcgatt g aqcagctccq c Ccaagaactt a tggacaagtt c ggccqtgggt a aatttccgga a ctctctatcg tcgttcagcg agagcccatc atccatgtga aaqagattgc cat tggctgc attattacaa Cttttcccgt aataaaactg gcattttaga gagaccattg caaaccgqag ggtagtggtc gattctcgat gaactataga tgcctggacg 'gctcaaatc ;tgctatacc ;gagatgcag g acttacccq c gtcctcacc g tgcctaatc a gaagatact a gattccaag c gaagatgaa t gttcaaagt g ctaagaatag aaccggaaac gccaactgtg St gttqt ct C gtcatgcttg ccctCcgtcg cacagatttg tttgcaatcc ttcaattccc ttatacttgc ttatcgctac a gca aa a t t tactcgccta attgaccaaa gattcaggtg tataagggct gccacagacc :tgcccgtgt ~aagtgcatc ;gtgtgcaga atggtgtag rcggaccgt a tcacaggcg ttctagatg aggcgccgc Ctttcgggg agtgttccg 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 ggtccggact gtaccgaccc tacttactct gttatagccg gggctgtcaa tgttgcattg Ctgtatctgg Ccggttcatc tgcttctcta ttgqataaca tcctgjgttga gaaggagcag 2160 3 /282 ctcgccagtq ctgtctatta tqctaccgaa gatcatccca qcattqagat ccgcttcaca ttaaccagtg tggagacaga gaaactcg( aaggacgct agacggacc tcggatttt gagtacgac at t tctga t ttaaagaag( ctgaagaagi aaggagatg( a ct acagcc ctggtggatc agcttcgtgc Ctgctqtctq atcaactttg ggagctagaa aagtatcaca gagcgact cc ggcgacgaca cgggctcgga gaagaqccga gagaacatgc tgqaaaccat agaccgttgc ccgacgattg ccaagacttc tgggttgcag accggattcg a tggagaaac t qgaattct c ttttcggaa g tgctggaga g CCaaccatg aggaqgaag tggccgaca, tggagaggt- aggtctggtg( Ictgatggctc agctctccct tgtatactgz agcaqgtggt gcctaggaaa cqgcgatcgc gaqcgattac tgctcgcggc gcaccttgqt agtctgtcgt gagtcttagt ttgctgagcg tcagtgaggc attcatcgtt ctgccttaat ttcgaggcaa tcaacttcga a tttagacal C taccqaaa( a gagagacgc a gtggagtgz t cactatcct C tagagtcgc a gctqgaaaa t ccaaatccc zagCcctcga tgatctgcc cctcatctc, Iggcattcttc tgtcqagttc ctcggagatc. atggatccac cagtcgactc tgttcatgtg qaaggcgcgt tqcqcggatg tatcgctgac tttqggtgca aggccagaag cgcatatgct ggttgcaatt gggtttggca Cgtttaccgc C9 aaggtaga( aggtatatc Ic tccgcctct la tcqactatc a gaacagtgc t ggtgttccg a gaqcaaaag a gctaaagct t ggaatagag t gCCgggcgc c ttattcatc, 9 gCcacaggcc( aacctgcctc I gaaagqqatz Ittgcggatct Iqaactttcct ctctccgatq atggtccact tatttgaaac gaagaaatca ctggagaaac ggtgcccctc ttgqqcggta accgcacgtg gcatacatga tatggcacga tcccccaacg 3c aacggttti a aggagtgcz :t CCtttgcgc Ic ttqatgttc IC gCagtttta It ccgttaaga a aqCgcttgg g aaaatgaca t ctatccatt c catcccaca, catttcgagc. 3 tacctgtgci 3 tcaaccggai ICtgttggctz cat tccaggt ggaactcgat ftgcccgattc atgcagcaga ggatcaagaa gagatgcgct ttcaaaaccc tacagcctat agtcgtatqt gtttggattc acgcggttga act ttgccta cccataaagc :t cgaagtgctc it tgaccggcaa ja gtacgtqatc Ic gaccttgcaa it caaaacatgg t gtctgacaca g tqatgaqgg a ggagatcccc t Cgtgqacact a qgcgcaaaaa a tatccccagt a gcttcqtcca aCggggaaac ICtccatggaa ggagcttgag *tttcgatgtc caagcgtagt gtctattgtt gcaattagca tttccgtttc tgtgtcagca cacgactaga ggttcctatg ttatgatgat gggtcccctc taacattgat cttcgact cc 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 agcaagcaga ttgttgaqga tcacctctct ggtgcgatgc ccttcgatcc cttgatgcty gaggqttcca ttagcagcat tqtggtaaqc tttgcgaatq aacagtcqac aattggtagc 4/282 gcagcctcag cgqgtgctca atcattctgc cttgaggagg tgtcqgttta cactcaaaga ccgacgatga acatggagga aagatttatc ggcccagata cgcaatgatt ctqcacctaa aagtttatga gcagatgctt gacataacct cctttgtqag accgaactaa tat atgaata gcagttt cat agcaggtgcg Ctttgtttaa tttgtcattc gactatcaag attcgaagat cgacgatgag tgacgaagat tgagccagtt tgccgacccg tttgatgtta atcttagttg aaaaqctctc tcgctatcgq gttctacaca aataatacaa cacccagatc tgtataaggt ccgacaggtg ggctactagc Cccgtccacg catgaagaaa gaaggtctcc gactatgggc tatgaaaccq gatgagtgat cctggataac tgtgatctgt at gat at at c tgattatcgg gttcttctta gcccact act ggctgccatt ttactagaaa gacaaat tat a attcggcgcc gttgatgacg gccaatatcg ttatgatctt aggcatcggg tqaaggtcgg gatctgaaga gcaatctata acctaggtcg attgttagag gtacaacata tacctaccaa tttcattgaa atgattaacc atatttgcaa ccccaggaga aaaccaaacc tgcctagcga tgaaaggcgc tggttacctg cttgtqtatc attcacgcct cgatgacgag tgaagatgac cgacaacctc aaagaccagc atgtctccaa agtggttaac acccgagtaa tgttgtaata tgaagct tag cacacagctt tataaataca acgtgacaat ctacaaggag tctgaaggac cgctacagtg atttactaac gcggtgcagc gacgagqagt agtgatgaag tagacatgac tacccctggg ctagcagacg caccacaaat acgttgccag aaaagtgcta tctcttaggt ctatctctqa ctctactcct atgatatcta 4020 4080 4140 4200 4260 4320 4380 4440 4500 4560 4620 4680 4740 4800 4860 4920 4980 5001 <210> 3 <211> 3850 <212> DNA <213> Aspergillus niger <400> 3 gcgcggggtt cctgcatgtc tttcatggtt gttctggata cccacaataa agtgtttcta gctgctctgt aagggtccat tccgttggag ctcagtctga ggtgagaact gcaatataca tgcaaacatc tcccttgctg tgtggtaaag tcgcaactga ttccattgac cctcaccatc aatagqcttt acggacgcca cagctgctcg aatggtaagc cgctaagaaa qgggaactgt gggaggtata ctattacttt tcaaacaacc ctccaagctt tctccctttc tgtcgaattg aggccatctc cggttctggt tgtacatgta tgcattgtta qtctgtccgc tctcaatctg tcggtgaacc ttcccgaaag caagqgggaa cgattqgcag atgccgttgg gactttgaag gggcatatgt atgcacagat ttcttcgggg ctcgcgtcca tgaacaatgg qgtcagggca 120 180 240 300 360 420 480 /282 qtgcttgggc tgttcctctg gccctccc tgaagctcac cagacattca gccagcca( ggccctggca gccatgtcat gccaatctl cctgtcaaac agatcaagtc ctcgaggat qctgcqgcct ccgcaqtgtc agccttgac tggcccatat tgtgcatagc taaccagct ggagaaccqa agttatacca aacccctcc aaagaagcgt cgtctgctga cacgagaag cqtttgacac tcattctgag agcacctgg ccaccactct caccgatgat aqcgatatc ctacgctcct ctacatcaac agcaccaac ttgcggactc ttctgacttt gcaaatgcg actagtgcta atcctacttg gtgcagttai ggcatcaaat caaccgtgac agattccgqc tatcccaacg gaacggcata caatqatcac. atctacgaca qcatctttgt gcggcactgc qtattctccg gtaccctgca aagctcgacc tcagggggat tgaccaacct ggttaaccca tttgqaggca acgacgacta tgacctctcq aaagcgccag agctgcctct tgctaacaac gacggctctg cgactgcctt tgccgtcaac gttgaaggag aatccaacaa tcccqtgttc caaatgqcta ctaatacata cgaqtcggac gatgacacca tcactcccct tgcaaaggac qtcgatgqag acaacctcgt cgtggcaagc atcccaggcg atgcagggga cqacttcaag tcggctcaat acgtcctatc caactctacc agctggagcg tctacaccqc cagccctgac aacgagatcg accccgagct tagcgqcctt gacggcaact gqactaccqt aagtctatcc t gcttcaagc ja tqactggca g gctccagga g ggaqctctt c cqgagtaa t acctgcata 9gqtqtatgcc g acaccggtc tggagcttgal Saggagatcal 3 cgcaggttcc tggttcaggc aaggcagcct gacgtgcatt ctcgccgaga gacacttacc agcgacgacg gtcaagggtg cctgacggca acggctgcct gccctgata tcc ctgata cgcaacgtgc 't ggccccgatt ic Ctttccgctg cagtcattcc agtggctgtc g tatctccaat g gcagatgatc c attgccaggt t attctcgacc t cgacctccaa ctgqcttggc cggtggcgtg ctttaacgat ct ctCt ccgc tcatccttcq cctatcccag I tgaccaccgc c qcaatqttca a ccgaaagccc a aatgggttac c atgtctatct c gtcctgcaac c gcgacaaaat a tatacgtata c tggcagctcg ggcataaatt ttttcttgtt cat cacggct catttggaac ggtgccccac ccagccttac tcccaatggt tcgggcaaga tctgacaatt qa gctg9tgga gcctctgcag zggttttctc :ggaaagtcc :acagcccgc ~tcccacgct 'tatacctct ttccctcct ttcaagagc gtcccacac ccggaggga gCgtacttc tccatcgcc gtgacatgg cttttCgcc ggctccgtg 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 tgggaccgat cgcctagctc caagatct ag cccacgaact ctcctcgtca gagggcgtga agttcctccg ctCCttgCc gacgaaccag tcaccqacgg cgtccagcgc cttctggaca tcaacacact ggcctcagcc actttgaaga qttctacttt Ccaccaccac atcacaaaca 6/I282 tactaaactc a ga aat accc ggaacctgaz accccacagc gtacgccatt agccgqcgcc cttcatcgac ctggatccag gttcattggc tqgaccaagc attctgaccg cggatccatc gtgacaagga agaggggcgt ccCttttctt tgtgtgtgtt gatggattaa atacggtgaa agtcagt tat ttatattctg gacagaaaga agtgattgat accaaccaac aactagacca gaaggaaaaa tttctctttc agaaacgaaa Saccgcagctc ,cctcgccttc aatgqcactcc Iaagcaccggq ccctatcccc gcctacgacg acggacaacg ggcgatgact gatgcgtggg caaacccccc tgtatagttc cggccccagc ttatcgcata gcccagtcgg cccccttttt tagggtcacc tcggtattct tccggtggtg gatcatgttc tttgcagtgg cttatgctta aactaactac caatcaaatc att cat caag caaatcatac agcctttcca caaggatggE ctcatccacc aaggtcttcc i ttcggccagc *aaactcccct acctaaccaa gcgtcgccgc ttggacgcaa tcgagacgga ttttctcccc aacggcacct cgcgtcctcg cctgtggcaa tttttgaatt tctcccatga gggcaagaaa ggggtgggag gatttgaatc tggctgggtc ttactagttg tgttgggagc tgtctgactg aatttctggt gacagggcaq acaagctttt aatgagagga itcacctaccc Igcggccccga Iccgaccaggg agctcacaga *cttaaacata aqcctqgcaa *gggtcccagc gttcaaggcg tgagttatgg ttacaccatt tctgqcaagc catacagcac atgggattgg tcccggatga ttatgggtgt acagcctcgt ggtcgaatcc cttgatcatt ccaggataga gtagatcagt tgcttcattt tctgtcaacc tctttcttct gacaggatct gtacaatcaa aggacagaga a ccaagacttc agacgcctgg atacgtcgtc cgctatccaa cagctaacaa tacgtgcacg ttcggcgcgt ctgqttagcc tttgttgagc acccctatac gcgcgacgca cccccagctc actgtttaat ggatcattgg tgtqgatgct ctggtatcag tqatgcgatt ccctgttgct tggacggtta tacgagatga1 gtatatcaat gctatactaa 3gtatctgaa c ~ccataagaa t ~aatacaaag a gactcatcca gcggatgaat gtccagccaa cttaactgga atgaaataac atacctacga tcatgatcac at gatggt cc atgaggtgag aaatatgatg ttccacaaca g-tcatccaca acgctgcagg tat gtt cat a gatgtagcta caggtgctgg gctttggagg cgttactact ttactggtcg tgtatgagac :tattcttgt -attatacca :tcacctcgc zggaacaacc :cagtacagc tgataccct 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3850 <210> 4 <211> 3139 <212> DNA <213> Aspergillus niger 7/I282 <400> 4 attqagtagg ctqcgctctt tgattctttg cqaggtacta aacccaaaca ggcaattgag atgttcgqga gagaatatgc ggqgatgcta tgcctgttqc agggatgatt atctccacac tagcgcgtta aaggtttagt agcctgagat ggattgccc 00 cagccccag taataaagt ctcaacctg gtgaaatga qct t tcct c agacttctc agctaggca, gtggaacacl tcgacatcgc ttggaggacc cgtaggttgc ttcttggagg gagctaqaaa ttCtcctgct qgcaqagcgt gcatqctatg gacatcatgc aaatatcacg tacggcacta gcgcttgacg gtttgcccga gttgtggacg ct Ctgccct a atgctggaaa tggagcgacg t acttgtggz t gcgatgatq g aaaaattaa g cttataaagj a attcccttc t cgttcccag 3 gatccaatg agacgtgcc. caagtglgcci tggtgtcaat agttctqctt tCacaatgat catctactaa acagcgatga ccagcacgqc Ctacgaacaa aggtcgctga gctgaaccga ca at cggtgc gagtggacaa tctggtatga tcgacaaagt tcgCcaagga acctcaagta ia cgcgtcgaz [g ggactgccc c tCCgattqt a acgttggag t atctttctt g Ctactaacg g aaaggatct a taCgaCtac. a aqcoaccaag, tCgttcgagc tgataccgcz ttqatagctt iCgttgtacct cgccacccgt tttgggagaa tCaaactgqt tgcgctcagt gtttatactt tgttctcgca CCCcagagag ttcagacagc tttcgaagga gtacaccagc Caacccgatt ig atttaCaa( C aaggCtgtc t ttgatttgz t accggctct a aaatcctct tagcctcac t gcaacttga a Cggagtcaa a aaccagtct 3 gccttgggc ItCttatgcti ttaacaacc( ttatatagac. gaactcgtcc at ct ggccc aqtCttattc ggaaaggata ttgctgacaa gccatgttcc gctctttatg taattccttc ttctgcacgg gCCgCcaact gccattcccg ga tctccgacc :a ccatgccac. ,a atttggggc it Catgqgaga c aaCctgtct c attagacat t agctgcact C cacttatcc a ttCcagcaa ggagcccat t ttatggaga, 3 aCtgacatt( I gtttgtcgci qCqttggaa CCCttcaagc agaacgcaaa gaactagctt gtttggtcaa tctacacttt Cggatcgaat gatagtgagt cgaaaagcaa gctgcatggc tggaagccgc aaaccggtgg tqccaagctc ggccctgcct ;a CCtaactagg 1c cgaactcagc it taCagtctac ,t gtacctgcaa C atgacgaggc t tcacaagcag g gcattgatct g acactgactc C atatttaact g gaatttcagg 3 ttctctagta :cttctttctt Icaccatcccg "tcctaacgac icat cgcacag tgctgcaagg ctactggggt aggattctca ggqaatgtc ggcccttgaa cgcacaagCg cgcaccggac aatttacctg aatcgtaact ttggcccttq 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 tcaagtcgac catttttgag gccatqtacc acctctgagc ttctttacta cgtgcaaacc cgcaacacaa cgatccttgg caactctgaa gtatacgaca Ccatcaaatc Ctacggtcaa tcgqcttctt tgacttcggc ttccgatgag 8 /282 gtcggcacgg ccattacatg ctccgacaag catcgatctg ccaccattaa agagqtcctc ccgtacgtca atgagatgq gaagtcaaga cttcccgcag ggatacggtq cctactgatg gggcttactt ctctgttcac agtcgaggga gacgcaggat tlggataatgt tagagtt tag cat ggagacc acaatactca agtggagtga tctgaggtat gaacatt act tctctcaatt ccggtcggat gctgacattt iaagccagaca icgcagtgqaa cagccaaccc cgaagaacct tatgtttata atagcatact caccaatggc gaacttgacc tgatgcgact gt ggt a agcg t at tca tata ttaatgttgc ggaacttccc gtagtttgga atcaggactg ctgagctgcg agccttggag gtcctaccgc aatgcctqca aatccatgca ggctctgacc tccgaaqatg ggtgttgatt gacagagacc cttccccttc accctgtcta acattgcccg tacaaggatq atcctcaagg catgctatag atttattctg aagggattgt tgagtacaga tgtcgatagc tcccacaaca agcctccaaa gctttgaggt tat tgagtga ttagtattgg caccctgaat aagatcggaa ttcgccaagg ctgagcaaca tttgagggaa tcatcatatc tgccatctct ctgacggaac tgtqgccgaa ctttgatgtc atggggatgt tgccgattcc atagtattta atttcccatc attgaggcaa atccgctgat tcgqcaaccc ttagctgcag tctttagtgg ccaacagagt tacctcgagc gtgatggctc agcgctactc cttacgatcc gtgtcttgct aaaagtgagc ttgcactgcc gatctgccag gagtttccaa ggtccgtgat tgaaaaccca ggcatacgct tttgtacacc taggctttta gtaccggttg ctgaatgttt catacttcag ggcggtcaaa atgagtggaa attccatcaa ttattctcgg1 ggacggcgac cggtgacttt agcgactcct cgagcagaac aagcagctaa aaggccgtcc qtggacgtgc cggagcgttg aagatgtcgc aagcgatgac cgtcatgtaa aacagcgctt tttaactttg ttgttttggt gatgtttcga ggatattcca ctaattgatt c.gagaattc cgactcccqc cct acattt 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3139 gatcctctca tactttccct cttcagcact cggcaqaca tatgtccttg cccacttgct ttacagattg aatccggatc <210> <211> 2940 <212> DNA <213> Aspergillus niger <400> atagcagaac agaacatgta tcttgtcaac gaattgattq atttcagcac ggaaatgttc aaggcatgga acaattgctt ctqacccgga accgcggatt gcaaggatgg atatgtggat cagatggtgt gaagaagatc tgtctgttag catacttcat aagttccaag gaggagtaaa 120 180 9 /282 tgtggagtca tcggactccg atcttcccag gcagagactc ttctgtcccc tggtggccgc ccaccaaggg agactgatcc tcttcttctg ggatcaatgg aggtcctggt cgccaatggc cat cqaccag ttcttccaca tatgttctgt cgccgccccc gcgcgaaacc cgagtacatc cagtgtgatg ctttacggta tacaggtata tgatgtacaa cccgaggcat acgtctacga cgttccctta gcgcata cat gtgacgacgg tcacggtggt ccgtgtcgtt taagagtaat tcggctctgc tcacctaagc ttgataaaaa atctggtctc gctgcccgtc atatctcgac cagtgtcaag gttcttcgag aggcatgtct tcctcctcca tccgtctaca cccgtgcaga gacaatgtta ggcact tact aacttctacc ttccacttca gagqaqcaga atcggcaatg cactacctgg tccgggcaac caacctctat cgacgagatc catttactcc cgagttctac caattacacg gcgactcatg cat gta cgcc gcaggtcaag atcgaatatc cagcgatcqg actgttactc gggttgggag ttgttgtccc tcccgggccc at ccccgt cc agcttctccg gcgcgcaacc gaccccggtc tgatcggctt acaaccccta ccggcttctc ttgctctgcc cctaccccaa gcgccctaca ccacggagag acqcccatct gctggtatga tttctgatcc acatacgact ggccccggaa tgcagcactg ggtcgggatg gttgactacc gagagcaaca aacaccatcc ggggatgccg gccgccaact atagaatggg caggtcacgc cactcttctc catgctttga cgatgtacta agtttgtggc gctacaaaca gttacgtcga aagatcccac attatttcct gttccaagaq ctcctggaac ctacaqcatt ctcccccgcc cqtgagcctt gggttttatg ttatggcggc ccagccggga cccgattatt ttatccttac acctgccatt actgcctcga ccgacgattt agtatgactt tgaacaaagc acgctgttgq aggatgtggg actataactg tcagtagtgc gttgtcttgc gtctgcgtaa tctttgacga atttcttcac ctctctctgg tccgcccacg ggtccccacc tgtcgctgag cgaggctccc tccaattgct cacggcccat aacgccagca ccggttcccg tgccccgact acggctaatt ggcgcatttc cactacgggc gccaagaaga caataccagg agcctgqaca caacaagtcc ccagctctac ttgcgccaac tcgtqaactc gtccgtgcag actcgccttt caagctgctc caactggctq gggttacacc gcaatttgcc taacggtgaa cttggtactt taagaagata tccgagagct qttgctgcct gatctcattc ggcatttgtg cat gagcaca ttgaccgtct aaccgttcgt gcggcattga acatqctcta qctatgtgga atgcagcgga ccaccgacaa ctcagtactc ccgtcttcaa tccaactggg cctactacaa ctaatctatc atcagctcgc gactgcgccq gaqgtcgaaa actccggacc gccgccatcg tcgtccaccg aaacagggtq ggtqgggaag aacattgtca tttgtgcgag 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 cctcggatgg agtgacacac ggccaggtgc gccaggcggg /282 tgtatgagac agcgcgt cat agacggtggg tgttggattc ggctgaagcg gtgcattgaa qgggaagcta gccattttat ttcaatcgca caa act qtgc caagcctcat accagacaaa ttgaggcatg tcgacatcgg gcaaggcatg Itggacatgac tggcggcaac cacgcccaac tctggcgacg gatgggacca gtacattgtt ca atct aaac gatcaggcta acccaaagga gaagatatga tcactctatt atctggtctg gatcgacacg accaaaacca gatccgtctc Igttcccttct IgatgtggcqE iagttactacc tacaacacaa gctttgcggt cagtgcaatt gccatatctt tctactgccg accaactggc gaagcaaagt ggcttcagct gcggggatct cgacgaa cat aggaaattcg cccacttcag atcaaccctt i cgggaaagat ggqagggcaa ccacgaatgc ttcagatqta accgatcatg tcgatgcaga gtqattttat tgtaaaagac ttaaacgctc gaaagaagag ggtggggacc gcaqtgqagg tatt cat cga ccggtacctc gcttqcgctc *tcccatctcc *cagcacgatt tccgaacccg gatctgaagt gctagctgtg caccttacga gtaqtgttgg acaacataac ccaagccatg gataaacatt cgaatccaag gccgctatcg tcgatagttc Iqagatgtttq I tcgagtttac cagtgqagg gtgagccgga acctgcgatt ccgcccaaag gccatgaaat aaattttctq tcgccagagc gtttccctgt caggggtaga ttgcgttagt Ctgttttgac ttctcatctg 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 ccggcacaac aaaaggagca tggcagcctg atttcctgcg ttccaactgt tcgtcqgttg atctccctga tcaagtccag <210> 6 <211> 4550 <212> DNA <213> Aspergillus niger <400> 6 tgaaccatca ggtgggacca cagagcccac cgtccagctc aaggcagctc tctattcgaa 2940 gaaagaggta ctggatatat cgqgtacttc tagctccagg tcgtgaagcg cacaaatact ggtagctacg tcgtatataa ggatcgcatg aaqagccaat actgcagctc ctct ctgttg tccacaaaag ctacctccgc gttggcgatc aacgatggqa tagagatata aattgctggc cagagqgcgc gcctgacttc cagtctctct gagcctactg Cgcgccgccq gaatgggacg ggcggaggtc tattcattgc ctgaatgatc caatcggggt agttcctttt tgttgggggg tctgtcgcta ccgccgtcat aacatgtgaa cgagtgtacg attgcattgc aggtcagaag gtccgcccqg Ctccttcctc tcttgtgaat cgaacaattc cgccgccgcc tgttagcacc atagagctgt tqtggtagaa acqccgcagc ttcccttttc acggtcctcg gtcttgcgtc tgttgcgagg tqgttctaat ttgcgagata agaagtggat ggagatagat aacttgtttt tccgccggac agtgtctgtc tcattcgccc tggctccaca gccgctgcct acttattcgc 120 180 240 300 360 420 480 540 600 660 11/282 ctctttatcg ccccatcacc aatcccatcg gatttacttt gtcgcctgcg aggtcactag tttctcgca cggccgctg ctct cagct agatggatt ccgaacgqc cgcctgcca, ctgtagggc( aaagcgtagi gtagtcaggc acgtggtttc gttg-acoLt- gtgcgacgtt cccgaaqgct agtgggatca tggtgtcatt caatacgaat agttaacatt gacggattac agagcctgtc tCgtcggttg aaccagcatg ggaaggagac tgacatcctg gaatgtggag qacggtggct cgct act cgc gtcaggatgg ggaggtgatg cgatctccac a tcctaaatt aacgcccgg C gctcattati t gaatggaga( c cgtaaagcac a tgggactgtz ztgctcaggcc gtctatccac tactggqttt Scccggqacct ccacatgtgg icgtcctgtgt attcgatata gaaattcgcg agtcggctgg tacatccagg gatgqccatg ttcctccctc acgcgtggaa ggcttgacgc ctggtggccg gtgctcctgc gattcgagtg attgagtgcc ggaggcacgt ggtgtctacg atca tcgact cgaacgattc acccgaggca t Cctgcctat t gtcaccacg a cactctacg -gcaggcgcc -Cttcgcccc atacgatgtg gactcaccq. ttctgtcag, *gtggtagat( ttctggggal atcgccttal at cgggaccc tgaaattgac ttgtgggtaz atagaaacgc CCgccgcagc cgattgctct tggaccgacc cgattcagac Ctgagtggga agat catcct aggtcaacgg ttgqgcagac aggttggcga tcCataacct tCtgcgaggc cggtggacaa Ccgatcgttc ccagcatcgt C ggcgctcta a gcatctgcc a gaccccgtg a agcgcaagc g aatcgagcg g aggatgatg. g aatggcaagi a cctgctccti g Cagagaatgc :aCtgcatctt :gacagtgatc tgttcacgac Iggaactgaaz itgatgcagge gcccgaatac agctagcggt gCaggccggt gctacgcgca gcagtggatc ggcqaccgtg gcctgaaggc ggtgcttctc agtgcgtctg CCtgcatgcc gtcttaccag tgccggctcc gcgqcccact gcqCgtggtc ctatatcgat g tcgacactt C tggtcaggc C tatacgtat g cagctccat c attgacacci a agatgcqagl ztaccatagac Lcgacacggac. 3 gtacatattc -tgataaccat ctgatttgaE tttggaattt ictgcagccgg gaaaaactga ggCgatggct ggaagttccg ggt cg tgca g ctggaatgca ttgaagccgt cgtaaagcag CCggcgqacg acccaattca Cttgtccaaa atcacqcccg cagtcgcggc ttcaaactgg cgcaatctgg atCtcgtatc cgacactggc t tctttgtgcc 9 cccgtccgct c cgtaccqacc c accacacccg ggggattcga L cgtctgctgc i gaggttqtga i Ctgtccatga acaaacCgac *gaggaagtat Ittggttacta tgaaattcga atgcagctaa gtattctgtc aCaqtgactt gcagtcctgt acqgtgcagc tccgtcgcgg tcgacgagtg cgcccacgga gaaagctcga tCcggttgga gaggcggtca aCCggttcgt tgtatgccat a aaa caca ct atgagttcgt ggcatattcg accccaagat 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 12/282 gcqactggct gtgcgcaacg acgacaccgg tctgtgggac ttttcggacc tcgcggaccc 22 2520 tatcccagct ccagcctgct gaagctggac gaagggtttg cacggtggcc ctacagcatc cttcctccgg gcggccgaca ggctaccccc gtggttgtgt gactccatca at ccagt acg cgccaccgac tacatcaagc ccggattgtc cgcgtccgca cagcgggcag gttgaactat atttgcgact attgcggatt cgtgtcggag cat ggtgcgc ggagggtgat tatcatgtac gatccaggtg tggtqctgtg cgaagtctac taaccaccct caaccaattt aagaagtgag atgtgccgtg tctttacctc tgtccgagta aggataaata acgaagggtt gtatagtatt gtggccaaga ccgcgctacc tgttctaacg cttggagaac ccatctct t c ctgaacatqg gaatggatcg aaggtcgatt at cat cctga gagaaggata ccqactgttc ttgcagaaac gtcagcgcaa atcccttcaa catcaccgcc caaaatcccc ggtagtgacc caccaaattc tatcaaagac taaagacggc tgatggagtc ctgtgatgag ttccgaggaa ttgtgcgcag aggccaagaa cgcgaqcgat tcgtgaacgc acccaagcct aggqacagga ccgccgtaac gcgcgatcaa gtgtcctgat gcacatctaa ttcctgtcct agagctacgt agaaggtgac gcccaccgcc ccttggacgg cgctggaagc caacagagga cacaccatgc gagtatgctc Cagagtcgcg gtaaacggcg gacaacacat gtqaagaaga agagaatgtg cagt cccagc attgcaccgg agtgatattg catggctgtg agccgatttc cttcgtacga gactgggttc cgtgccgtac taaagtagtt ggtgcagqcg cacgatcttt cgacatcacc cctggacgcc tggcgaggac ttcgcataag gtcgaaggtg ggtccagatg gcaagctaac tgggttcaac acagctgatc cctgattgtt cctaqagact ggtccgtcag ctcacccctt gatccccctc ttccaacccc atttccgcct acgatcatta gagact aa ca cttccggttg atgctgcgaa agccggattt attcaactcg gtatcctgta ggattggtcg gacctctgcg ttcctgcatc ccggttcaga gtgggattca actgtttcta atcactqtgg ggagtggtgc gatgtggaat cagCagggag agtcaagctc ccatcgcggc tcagcggccg acccgcgtct cgaaatggac gaccgtgcqg cagatttcta aaccactgcc ctaccaatac gaacctggac acgggcggtg cgtatgccac caataatctc gcggaccgtg :ttgaacccg ~gagtgattg ~tagcagaca atggtgttag cgatgcccct tcgatgcaga acatcaacgt cgctccaaaa gtgccaaact accagaactt ttccagccaa acaccggact aqgcattgtg accatctagg agatgccgga gtatcatgqg atcagctctt acacgttcga cggagttgga aagaaatgcg tcgtgttctg agctacacag atcaagtaac ggcttggccc cgcttctccg acattcgaca aacccct ccc Caqt tcccca tctcacgaca gatgctatgg aaggcggact tggcttggaa 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 4020 4080 4140 4200 4260 131I282 tagtagaaaa agtgaaaaat ttgtagatgq atgtattgtt tgtqatgata gcattagtct tgagaaqtat gttgctcgac acatgaagat aattttatcc gggaaaatga tagagattaa atcggttcgc atatacqaag tcggatgttt acgtagtacg taqtqgctac tctatcgagg ttgatttgtt ttcgtcccat ctgcacatgt actccgtata aacccaagtc tgaaagtatg aatgaacgaa tcgacaacac aagcaaaaga agccccattt catcttattt 4320 4380 4440 4500 4550 <210> 7 <211> 2660 <212> DNA <213> Aspergillus niger gaatgcgctq ggaggaaacc gcgtgacttt tcgaggcgtc ttccttcctc agct act tgc acccccccct cgcaaggtac tagggtttca ggccgttcct tgcggccgag ccaggagqaa Cttcttcccg ccgtcccgac cactggtgag cagggtcaag cggt tat ctc tcaagatcac cgcaatgacc tccctcaccg aaaaaaatgc gcaatgacgc ctgcaaaggg atcgcctaca tccatcctct tttttctatt tgataacccg ccatcctctg gcaacaatga CCCttccagc gtccctgcgg ctqaagtctc gagagcatqg tcgcactggg aacggtgaga aagaccgatc gatgacaacg gctttttata ccgagaatga gtctcttcat tgttgatagc ctaaggtagt cacccgacgg gcttgtgatt tggtcccgtg aagqcaccgg gcccatcgag tctgggtttc ttgatacttt tgctgataag cctactcatc gagtccttcc aqgtccttgq atcacagtgc tctctqacga atcagaaccc accacatcgt agqagcgcga ct ggctct ct agaatgataa tgctctggat tcccgttgtt ggagcttggc ccatgagctg catgtgattg tacacctcct cattgatcac tgtgtccgta CtCcctgccc ccatcaccat agctgctatg aggtaacggt cgacgggttc ggctcgtaag tctcttttcc Ccgcggctcc ggtcgatggc tggcatcgac gcatttqttc atctaacgca ctgtggctga actcagctgg gtcgccttcc CttCtctcct Ccagtagctg agttcacttt agqtaccqta ctcaattcat ctggttqgaq gccaagcacg tccaagccgc ctttgggatg ctccccaaga gacgttcaga aagctggaag cccggcgtga tactgtaagc acttagggtt ctgactcaac gttcctgcta CtCtccttcc gtattttctg atgccctctg ccttccagac accggccccg cggccacggc gtgccgacca tgcacgcatt aggtggccag agcacaaccg gcgtctgggt cctatgatct agcagtacac acaccttggt Cttcgagtct 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 acggtggccc tggqtgctct ,ctagcagca tcaacaagaa gatccagccg gtctacaatg actacgcttg gaactccaac gcgtccgtga tcttccttga ccagcctgtc 14/282 aatgtcggtt gtctatgcct cacattgccg tctcacaaga ggatacaccc gtcttggacg attgagtctt aacaacgccc aagtgcgagg aacaagcccg tttgacatca gttccgggac tgcaactggc tatgcctccg attggccagg atggtcccga gaatggttct gcagatatgt ttatatgttq gtatgagaat tgaataaggc agtacgtaat cat gtagttc attgaggaaa act cct acag tgcttaccct gtgaatctta agcgcaacat agtacgagta agagctcctg gctacagttc tccttgcccc atagctctaa aagt cat cga accgcaactt tcctggagca tgggcaacaa ctgagctgga ttaagtccca tggaccagcc aaagacgtgc ttcttaacga cat ggtat ct gaatcgatcg ccggccagta caatggttaa gccactgaac ggacgatttg taactctgct cttcttcaaa tgctqgtcac caacctgcag ctaccgtccc ccagtccatg cgagagcgct ttaccagcgc cctttgctac gqctgttggc cctcttccac gatccctgtc ggcctggact ggatctqqtc tggcaacttc cgagtcgagt taccaccgca tagtttgagc atgagttttg catttacacg gtttacatac aaaaaccact gcacccgtat gtcagcgaca caattccccg tatatccccg tccgttctca atggcctgcg gacaacgctc tgggtttgtg act gggcaga tcggctatgg gctgaggtca ggtgactgga ttgatctatg gaagccctgg attgtcgaca accttcatgc ctcgagttct tatagacttt atgcttgtca tcactatagt catataaata agtgtagaaa cccatagaag atcgtaaacc cggtcgctgc agtatgctaa tcttcgcttc ttggcaacqq gtgacggcgg ttcctcgctg tcccggcctc acgtctatga gctacgtcag acggctacga tgaagcccta ccggtgatgc agtgqcccqg atgagcacac gtctctatgg tcaaccgctg ctqqtcattt atgcccacta gcattataca gtacccaaac actaqgcgta ccaagccata agcagaaaga tggcaaggac gcaggacttc ggagatcctg tctcaccgac ttacccagct ccagtctatg cat ctactgt tgtccgtggt cgactacctg ctcgtqcaac ccaccgcctc tgatttcatt acaggctgaa gggcaagaag tggtggccac gttgggaggt cggtga~act gtcccgatcc tttgtacttc cgtctggaca cagacgtctc agagcct act gaaaaggaaa 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2660 <210> 8 <211> 1680 <212> DNA <213> Aspergillus niger <400> 8 aaaacgtgcg cactgcaccc actcgttccg gctggggtct agaaatctgg acggtcccag gcagatcggt gcctgggcaa aaccttgata aaaatagctt gttcgatctt gagttagaca gccaattgta tactcactag agacacttga tgattcagtc tgtgacgtac gtgcacctcc /282 acactccgtc gaaacttgcc atca tctaga cctcctgcct tccattctcc gcaagcagtq cggt cat tgc gagaattcca tgggcgggcg acctttcgtg tgggtcggga tacgtggaaa tatgacttcg t cgccaagtc acgatcagag gaggatttcc tggggcgtgc gaactgaagc acggtgaaat atctttctcc tatttcggta accaagaagg gctttcctta cccacacata 'gatqgattat ,taatctagtc i gggatataat ctttattatc tctcattcat tcctagcggc agcgtcaatc gactcctcga cagtgcgcga taccagaacc tagatggcga acgggcagac acctagatgt aaggtgtagc ccccagctgc agtctggcga aaqcacaag agggcaacga atacgagctg ttttggacgg qtagttttaa ctatatggcc tatatatcta cagttaatca gtgtccccgt iacaagcagaa *aaagtcgtgc *gataccctct cat gaagttc tcctgctccc acatcctctg agccgacgag gcaaccacct cacggcgcaa cacatacagc gtacaacqat aagcacaggg cact att gag gacagctacc ctcaatggtc aggaggqtct aqtgttgaca atgtgatggt tgacataatt ggttgatact ctcgggtatt ctttccattt tgtcccqtat z gggcacgcgg aaqtcaaagt gtt tat gacc gccactagcq acaaattatc cgcaccggtt gcacctattc aataccaccc ccgcaaggca ggggggagcg aacgccattc gcctgatatg gacacgatcg aacatatcga cttgccggcc gatctggctg acatggggtg gacqtggagg atatggtcgc tttctggttg :ccagcatgc cgccgcattc t =ccaacctc a ~taccaacta a agatcgggga catccgcatg ttgcaqgaaa tcgtacatca tcttgacgac tggaggacag cacttgacac atgttacata cgtattctgc gaacgcaggc tacagacagg agtggtaccc tcgccaaggt cggggaagaa agaatgccga gctttggcga tagatgatgc tgcaaagtga1 atattctcat attttgaaaa1 lggctcggct a :aaggtcgca t lttcttgatg c 'gccgaqcat t catcagtcga cgacttgcag cqacccgcct cacttcacaa tgcaacgctc actccgtgcc atccaccaaa cagcagtaac cgtgtcggca tgggtcggcc agtcqacttc agactatgca ggaagccatc ggccacgcag ctggatcgtg gatcagcttc gactattqtc ttcggccttt ccttcgacta :gccttgatg ittgggagga .gccttctcg .gagaatcta .tcagcgcag 240 300 360 420 480 540 600 660 720 780 840 9,0 0 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 ccaagttggc gcgctccggc cgcgctctct actacccgct cggtcatccc gctgcggctt <210> 9 <211> 2590 <212> DNA <213> Aspergillus niger <400> 9 ttacatgctc tgtgtgttgg taaacacgct gtcacattct tcatgtcctc tggattgcac 1680 16 /282 gataacttti ttggcataa( aaacgtcggt ctttttaggi taagacacct gcgacgatgz gccacagctc aaaggcgcac tacaaggcgg ggacggcata a aga tcat ct ggggattggg ttttacaact gttcccgagc cctaagacac agcgaagact agcaccaagg tacgcqcqct gccgacttct agcacagagg act ttct aca gacggctcga gaggatcttc gaatacacag atcttcagca aggacccgct actgagggcg tttgctcgcc aaatgggatg agcaactatg ccgcqtctcl zcgacatttt( ctctttggtl agcgcagaggz 'ctgtttggai itatatgtcaz ctgattatgt ctcccccgcc act tcgagca tgaaacgcaa tctcttggct tcgccttcac tccaccacct aagtcgatgc aaaccagcct gcttgacagg caagccccga acagtgacct ccgtagtatc ccagtctcga ctaccgccgg ccaacgagcc ctgcagtgct aagccacgtg gcggagactc ttcagcctat tcgggccgga cgtcgtacca gattgtataa taatcaggga ccaaccggai 3 aaaaagtat( -tgcatcgagz a cggtttctgc actgcgcaggt ict at atcct c cgtggtagac atttactccc *gaaagtcatc cgatgtcatg tgagtcggag agtcccgttg ggaaacaaac tcatctgcaa accgagcctc cgtgacgccc ctcgagaaac cgacgagttt gatcaacgga catccaatac acgtgcgcca gtatctcgaa tagcacgtct caatttattt gggcgtcgga cttcccggcg aaaggctgtg gaatgcgagt tccagacgga ccatgggcaa tgatgaaact qcgggcgagE igacatagatE ggcgatttgE accagaactc ggacttctgt caactgaaca Iatgaagttct gatatctcqa gcctttatgc cat gttccac gcccaagcac acaacccaaa atgatccaac atgccagtgt atttgccttc gtcctcggaa ctagccgtat ggccaaaacc gccctctcca tccgtctcag cagctccagt tacggcgagg gcccaat tag ggatcgtgtg tcgtqcccgt gacttttcga gtggaagcat cggggtattc tggctacaaa atcaacaggg iagagagcctt icagttgaccg i tccgcaggcg gaaactaatg ccctcttaca gcatccccga ggttgtcgat cacccggtca gcccatccga caaatgccat aatcaatgat ttaggaccct caacgactcg cggttaacat gccagctcta tttccqgcta actctccaaa cacaaaactc tggcatttga actcgggtac atctggtggg atgagcaaag gtgcacgcgg tat ctaacga ttgttacatc gtggagggtt accttgcccg ctqatgtgtc ctgcgggaac a ccccgcatta tttcqacaac cggcgcgaca agcaaaggtc cgacattcga caccgctgta cggatggaca gcatcacgag ccgggattat tcaggtctca cgaagatcgc gaagaccgat caagt act cc cttcggccga tgatgaaata tgqtttacct tctggaccag cagcgtagac acaagaggga cgctaacgcg ggtgaqcacc tcttccggac tctgccggag ggtctcggtg cggaagccag cgtgggtggg :tccgagcgc ttaggagat ~gcccaggct ~aggttagtg 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 17 /282 00 00 gccctaccaa ctgtctttgc cactagggtt tagacggcgg gttggaatgc ctctggagca tgatgttttt gtaaaacaga atctccagaa actaccaact gatcaagctt a ct tact acg agtaagcact qtcaacaatt agcagtcatc tctgaatcct atcagtgggt caccaaggga gttggcgcag gtcccctaaa agctggacaa tttgctaatg ttacccgtta gaaacaaata ggtgagacat gaaaatcaaa tctcgactga tgqctgtact tgtgacqgqt tgggatccgg tctgcttagt tgtcaacgcc tat gcagaaa gttgtggtac attctaccgc aqcttaccga cctcacccgt cgagctgata acgctgcacg cactcgacca caaatggagg ttactggct actgcqgcgg attaattctt ttagagtaca tcacgtcagg agtagtaatc ccgagaccca ccqtaagatc atattacagt tctcgagcag gcaaggattt agctcttgtc ggggacacct gatggcctat ctcaagtgcg aagctggaga gtgctcgagc tagaaaatac tacagcctcg gaaaggatta gctgccgccc ggtaaaccta acggatattg ccgtatgcca ctgtatcaga tttgtgtcgt attagatttc cagaaggtcg acaccagcta tagataagct cagtacaaca ctatacacgg 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2590 <210> <211> 3080 <212> DNA <213> Aspergillus niger <400> ggtacagtag ctaatttggg tttttggtca aataatattg attgcgtggt tcgqactccg agtcgttctg cggtccgaat ccqataagca tccgtctcgc ccagcatgcg acgcgattgt ctggctccga ttgaatccaa tgggttttag gccatcgctt ggcattggca agtaatagtt tggcaggcag ggtgggaatc gggtgcattt tgacccagct agtgcggcca ctgcctagcg ttcttccggt ccatgaaaag ccaccagata gctgaaagac tttggatgta agggaagaaa at act ccaag aatcaattgt catgttgcaa agggttgqag gcagaatctt tgctagccgt atccctcgtt aacaattcga ctctacacag ctcgccgcgg agcttgtcga ttgtcaacac tctggagaca aagaaaggaa cagcttgcca cttacaggat attgcaacaa acccattgct tggacgaatc tggagacatq ccttctggct actctgtgtg cactcctgtg tCCcctccgg tcgcgctgqc ctggcgaatc tcgatgcttg ggatttcatc aagtgagaaa aatatgggaa cgcgatcccg tatcaacaac agccttttgt caatgatgcc gtctcagaaa tgttgtccct ctccctggcc ctggcat cat acgcaagaac gcaatacggc ttcqccggcg tgccgcggca tgtgcttatg tagcattggc gcgatcgccg agccgacgcc cagtatcggc attgtctcgt agttataatg *ctcaaggtct gcctcgacca gtcgaagatg ctcgatcagc cagtggctgg 120 180 240 300 360 420 480 540 600 660 720 780 840 18/I282 00 00 accaggagga tgcgcagcgc cggtcgataa cccagagatt tcatctcccc cgcaaaagat tcacgccgtc cgggcagcaa ccaagttcga gcggtgtcaa aattgctcgt cgtgagtatt cccgaccccg gagtaccttc gacgacgaac agaccgttcc gcggcatcag tgtcgacacg caacatcacc gqtgaacaag gcgcacaaca aacgaccttc tgacacccat ctgcctgaag gctgggcttc gaagctgttt tgatcagaat cgqagttgct oaattcctag atgagccgag tctccaagcc aggtacgacc agagtactac tgtcctcgag ctgttcccgg catatttccc cttctcaacg gagtactcca ttcggcaagg gtggccaaac gagatgtaca ggcagcttcc aacctgccct caatcgacgg cat cccct cc acagagcttg tgccgccgac caactcggct ccacatt ccc gccaagcgag tCgtccggtg taacagcagc attcaacccc ctatgccccc ggcgtggttc caagcagtac1 ccatagcttt aatgacatct tcagccgcgt gcgggcaagt c :tgactgatg t ;aqactgttg c atccggtga c tgtagatgt a tggccagcga gccagggcag ccacctttgc tcccggatga aaaagaccac gctccaacag attttggcaa tgaacgaatc cccagagctt cttccttgac cggtqactga aatcgaagct aacgagaacg ctgccccaag ccttccctgt tctgcaacct acgaaggtac acaggtatcg atcttcccgg gaaatcgcct cagaagqaag :actcgcaat )agccttcgt ;cagatatga ;tcccctttt ~cacgctggg I :qacgggggg c :cggcgcggg C 'tggattggg a tactatata t caaggctgtg cttqgtgaac ctactaccaa tctggtcgac tgctggtctg ctcgtcctgt ctacactccc cgcctcgtat ttccgtgqag cgaggcggac gttcatcact aattgtgtag agccttacct tgatttccaa atgtagatac gatcggactt act tacttcc gatctggctg ccacctgtcc gggaagccag ctgtgcagaa tcgccaactt gagtccattc ggttatcttcI -tctgcgcta :ttcttgaac ~cagtcgatc c ~attatcccg t cttcctgac t atggtatga g attaactggc tttgcgacca agcggctctt tcaatcgacc aaccagcggq gccgatgtca agcgcctcgt tctgaccttg ttggtcaacg ctcqatgtgg tctqgcgaac tCCtttcatt ccagtactat Ctcctatggt taaccggacc gttggcctgc cctgtcctat ccgaaccacc ctacgtgact ttccggcgga ctacctggcg tagcggtcgc ccaqcat cat tacggcgccc 3tgggcatgc :ccctgctct Jgatgcaatg :gggcgcact ;ttgagaagt iattatgtat 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1B60 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 tccttgcatc qaaaataccc ga cggcacca gccgtgggag ttcaqcaact ca cca cat ca ggatttcctg gataatacga gctacqgctc tqaacgatgc atagcaaggg gcattgatcc ggaatqccac tgaggcagtt accgaaccca gaacaatgtc acttcgagcg ccaacgagac acgttgctgc aatagggtct cggcggtacc tcgtctgcgg gtacagagcg gcagaatgat ggtcggatgg ggtgctgtcg 19 /282 00 00 gtgatatgtg ttcattttct gttatgaccg cgtctacgga catgcataat at ccaatca c caatggccac acaacacatg atattatgtg cat taaacga cttcccttct caccagtcag tactccgtga ttaacttacc gccgttgccg cttcatgcgt agagagaatg gcacctt cat ttctagagat aagaccccaa aacccccgaa ccgcttctag attagccgta gtttagactg acggtaagga acatgcttcc caacccacta attaagcccg cacggcat ag gggccagttq tgcgtcatat cctcagaggt ccaccccgcc ttagtggcta acagqggcat ggctgagcga tgaatttccg acatggacag tcctcccatt tcaacgcgac gtaaggacga agagaaaccg tgcgatggtg ggatcaccct 2700 2760 2820 2880 2940 3000 3060 3080 <210> <211> <212> <213> 11 1890 DNA Aspergillus niger <400> 11 gaggatgata cagctagtct gtgaatgttc qttgcgaagc aaaagacata agatcccccc acaggagaca tcgccctggt ttgcaccggc gggggaaggg catccagcag aattcattac ggcctgctgg gccaagcgct ctcgccct ta attggcactg tccggtgqct acctgtgaca gtctgatggc tctgcaggtc tctaccgctt agatgtcgtt ctgcgatcct gcctggccag ccatcgcttt caatagggaa agagcaggaa agacgctgaa catcaaaagc cttccaaaca ccaccactgc ccacgaaccg acggcaccaa gttacactgc cgagccgcga ctgctatcct cattccgctt tgcagttgga tgataccaga cgtttgcata cccgtttcca tcccgaqcta ggcgccttgq cgcgtcaatt tcgggattgg atggtataaa atcttccact tcatcccatc tatggccgct ccagagcaac gaatgtggag cgtgaccgcc ggagtactgt ccagaccggt gaggcaaagt caggggaact gtgatcgtcc tgggagccga agaatgcttg agcgaaatga caccatcagc gcgtatctgg cggatgtaga accacgtcca cagactccaa aagatgaaga cctctgacgg cctcccttca tacagctcca gagttcgtcg gcctccgcct gtggactttt gtgccccaat tgagtgctat cttttgccgt agatccacgc tacacttgaa gctttccctc caccgtcggt gtaqtgttat gaaaatt Gag attccctacc gcagctccca ctactgctct ccaagcgcca agcctggcac actgggccgg tgcccacccc gggtgggcat gtgtccaggq gtcacgcggt tatcgccaag cactcttggt aqggtgcttg gtttttgtca aatgctgcag cctatcatca ctgctcgata cttcaaggag agatagccct gtccctcttc cttgaccgcc ggctgctcgg caacgaqqtc tgccgtcctc ctccgtgccc tgacggtgac cagcgaggtg 120 180 240 300 360 420 4 540 600 660 720 780 840 900 960 1020 1080 /282 agcttcgatg atct cggccg gccacgattg gatggtgatc tccctcgttc gatggttcct ctgacctccg tgtatggggt tgagtgatgg tqaaaagcca gttgatttaa tacgcctttt acaacaqcaa ttactgcatg cctggtacga gtgataccat agaacgtqag tgtgtgagta cctttgccga ctgttggccc tttccgtctc tcgggattgt aaatgagagg atagttcaaa ttgaaccaac aaaatattat atcattggta act at ga cc gtggtacccc caaggtca cc cactggtacc caacgctgag ctttggcacc tgaggatgct cagtagcqag tgatgccccg ttggtctttt tgtctttatc gttggatcat gtatgtctgt atccaggact tgtctttagc gactacgcct gtcgatgcca acggtcaccc tggatcgtcg gtgactttca accatcatcg gtcgttgtca atgqgtgtgc ggcccggggc ttgttagttt cgtatccctt taaggttctg cggggatatq acgacttcag gcagcgacac acagcttcac aggacttcga ccagctgctc acatcgagca agtacgtcta tttcgacggc tagttttctc gatgttatag agcgcaaata actgttcaga agcttcagac cggcatctcc caccggtact gggcggtgtt ggaggatgac cgctaccaag gaatgaggtg agacgttgga aatggtgaga ttggtactcc tttgccttga aaatattacg tttatgtcaa attcacccca 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1890 <210> <211> <212> <213> 12 3080 DNA Aspergillus niger <400> 12 ttgttgtgat ttaatgtccg ttcccctcac Ccctcaataa gcatgcatag Cgcgcttccg ctgcatcttt a at gttcgt a agaataaggc ccgtgacctg gaatggcttg ctgctctcca tgctaagaga actgggagga gagggaaatc tggtcctgat tgtccccagt aatgccggga caaaatatct cttggccgca tgccggggat ttccaccacg attaagttcc cccagggtcg catcacattg aatgagtggc tggccatctc aagccactat tctttttctg accgcggcta tcagaggagc atataagctt ggcctcaccg ccggagcccg ccttctataa tttttgcttt ctCa tat gag gttatccagg ggaaatcaat tgctgcagaa ccgattaatc agctttgctg cgatcgctga cat ggcgqct tgtccctgca cccgccctcc ctaaccggtt tgcctcctta tttgattgcg cagctgcatg ggtgt cat cc cgcctatctg tattgccaga tagctttgct gtttctcaag tcaaccttcc tgcaagggat gacggcccaa gttcctcgtc accatggtcg actgttaata caatactaca gagttgattc tgccgttagt cggactccgt gcaggaacat agattaqatg atgagaaata gcataatgca acccactgca gttgtctgct ccttttcccg 120 180 240 300 360 420 480 540 600 660 720 catctcqgca ggcttcgccc ttgccgcccc tgccctggcc agcgtcgtcc tggagaccgt 21/282 caagtctgtt tttgtccgtt gtccacccct gtttcctctc gatccataag tctcaacacc atactctgtt tggaaagtcc cagcagaaaq gtatagcatt cttqaacgag ccagcagagt ggatgqtgaa gacggagtac ctaatggttc cctgcagtac caactcqtac gacagaatag gggcacacgt atatattgca gacggcaccg gcggtcggcg agcaactact tacatctctq ttccctgacg atggacatct tggcgggtac cccgtctgcg gctacaagag agggcgctgg cccagcgact gctctggcgc ggcaaggaca gcagatgacg gagggtggtc accttctcgg ccggatgagc aacgctgcgc aagagcagta gactatacgc tcggccttgt ttcactgttg qccgatctcg attaccggag aqt cca tt ca tacgagtatc ggcgatgacq accgttccca ggtatctcca tcaagtcccg acaagaccga gcacccaaga tctcqcagcc cctcgacqaa tgtctgcgtt gctaatgtcc ttctggcgct ggccaacaag cctgaatgac agtcattcct1 ggaagctcgt gtcagaacct cctacggcca ctgctgttgt tgctgaactt tgtacaagag tgaccgggtc gCtcggcggc atgtgtgcga ccgaggcatc actcggattt agactatcaa atgtccagaa gatctccgtg ttcccgacgt tgctggccaa aagatgtaag ttgcctacgc tcctcgagtc actgacaaat attcaccccc cgtgcccgaa gtcgtaccag gaagtactac tgcaggttct gacagctacg agccctgtgt acatccttgg attaccagtg tgggcgagct ggaggctgct ggaccagttg gttcttggat ggcttggctg tgcqaccact cggatctacc cattgatctc cgtgcgtgct gtacatcact gtcgggaagt ggatctgttc cgggggaatc cat cgtgggc agtgttccca cgagactact gaccaacgac catccctgcc cacccgcgta ttccggcgac acaggtgtgg atgttcccag gtcgcctggg tcggatcagg gagcagtaca ccttagtatg1 aaacttatat ttgcggggat gcttcctgaa gcgaggcagt gqaatgccac g gataccagct qaggaqaaqc ctggacgaca aagaaggcaq gtgggcacag cagaagctgc atctcgccga tcgcagacta ccggattgcc cgtgttgggt acccagtact aacaaccagg atctcgcatc aagatqcaat accgacgaga gagctgccac tcccacacaa tgcaacctca tctggtacgt gcggcgcatg gaacatgccc tggacagctc tggagaccta ccaacttcag tatccatccc zgatggtcag :gtcgcgctg c -ccttggctq t ~ggctgccaa g ;acggqatgg g Ccacaatttc tcctggccgt tcaatgagca gcgtcaccca ccaaccagct gcacaacgca ctgttttctt ccaaggagac tcaaagagca ttggcagttt ttgacattcc aqaatgatcc ccttgccggt tgaattaaag acgagcctta tggttatcag atcgcctgct tcggcctgat tgtaccccat catgtccaac gtacatcacc cggcggcttc cctggacaag cggtcgcgcg agatgattgt ,tcggccttg tgaacgatg .actcgagcg ~gcgatgtgg jatccggcga 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 22/282 cagggctggg gaggatactg ctgtgtgtgg acccttaaac ggaccctgtt agcggacact ccttcaccac attgtgccgg ttccccaagt aacgcctaat agtggacgtg actatagaat taaggataat cgatcaactt tgtttcagtt cctgattatt tcacatccat cactcattat tttgccaagc cggagtgaag catct acagc caattgttta gaaacaagct acccgcaagc ct actct ct c tctttacttt tgaaggaggc gatatgtgca ccacaaccaa ccqctgtcag taatctacca ctqtatccag tctctctcca cattctcctc ggttcttgcg aggcgttaac ttagcttctg tctcaaatcc qcggcggtga tatgcaaqcc accacaccat ccttctcttc ttgtaagcag ttataatagc catagtcacc gtcatgtcat tgaaaccgcc ctacttaaac tcttttcttc tcttctctac 2640 2700 2760 2820 2880 2940 3000 3060 3080 <210> 13 <211> 3598 <212> DNA <213> Aspergilius niger <400> 13 accggagcag aggaacaagc ggagaagctg aaacgtatga atgctgagta cgagcaaaag ttccctggct a catatct cc agatgcgtga tgagatggct gtgcgatatt atactgcaag Ctccttgctg cactctgcct agtataaagt gacgatcttc atttactatc ttgtgagaca qgttgtactt tatcctaagg tctttcaccc tgcggtttgt ctggcatagt gaggattgac gtctacccaa gcaaaggatc catatattta aatcgctgct ctgtccggaa gaccaactag cgtcgaacgc gatggtaaaa acccgggagg cgacaatgtt gcgaaccagg agaacaaact gtatgttctc acttttgtaa cggggcaatq acacggagca gggcgcggaa aacaatgaat ttacaagcca acaatggctg tgccggcgaa gtgctaccag cgcctcctct tcagccatta ggacagccat agggataggg ct agtatat a tcagtatacc acggtcgcaa ccgatcgtga gtgctgacag actggagcag acccttcgat tatttcggtc gtaatctgca ttatgggaag cat ttt cata atggggtccc ttaggccaat gcaacgtcgg gtaggtatgg tagtagtaaa caacgacttg ccgggatgtc ggtggaggag ttcgctcctt tccgctaaga ttcagcaggc catgcgattc tggaacttgg cctgccttgt gtatgacggg ctagcactcg gagagctggc acaatagctt ctgtatcgat tgttccgcgg tgttggtctg atcatggagg attatacagg taaaggcaat tatagttcac gctgcgacat atctatggag tgattccgtt cttacgacgg tccgtatttg gcaggccagc aggttggaga tgatagqgaa tagtagt ccc atggccaatg 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 accccaaatc atctttcatc ccatccacgc atgagcaaac atgcatggtc tgcgcctagt 23/I282 00 00 atgcagcatE aacttcagcE ttctgtccat t acagcagct ccactttgtc tgacattgac gaagct tact tcacaggcgc cact tagagg aagctgcaga ccaaagctaa tagaaacaga tccacggcgt ccatcgaata atcqcaccat atggacggqa ccggcggtqg ggccatactc tcttctacac ctggcaactt tcaacgcaca tccccggccg ttgacgcggg ggaagtccta gatqcctcag cggccatccg cagataatga ctttgaacta caaccatqct cqaggccggt igggacattgc i ccgtggact *gtagacacgE cgactqgttc g gcgacaatc aatgcggatt gttacagatt gttgccgagc agcaagggac gggqcggaac gctagtctac catgtatgag ggttgactat acgaagctaa tgtcaccgac caactacacc ctcctatct c cccaaacatg agcaaacgcc ccaatggaat agacggctcc tatgcgcatg cattgtaatt atctaacaaa cgccctcgaa aatcaagccc taaatgtggt tacgagcgtg atacgaggtc gtttaqaaac -ctttggttat tggactccct iatcgatcagt agaacattgt gagttgcacz tcaatgttaE ggaaaagatc agccatctgq gctatacagc gagtacatat cttgtcaagc cactggctac gtcgcagacq gacaacagtc ccctgggacc acaaccagag tacaacctac tccccacccc taccacgacc aacaqcgccc gqttcagca tacatctgga cacgaataca ccaqtatcca tcgggtggca aacgatacac gtccgggact aataccatga ttgtggaacc qgggtgccta cctggcatat tcgtctgacc cgcagtgtcc tcctggagcc t gt at actt c Itgtctgctcc I gactggtctt acaataccaa ttccactgac tcagagaggc cagaagggac tgacatacat cgacatatca cctggggcac tatccgcatc gcaacaatgc gtccatccga gatcatacat tcctctatac acggcggccg acgcaaactt tcgagtctac ctcacggtgg atcgtctcac tgggcgaagg gcacaacgtc atccttattc acggcgtgca tcatcgacaa Cagatggaaa ccgqcggctt tctaactccc gctqaagaac agctttcgtc cgccaaacgc Ccaattactc gtctttcgqa cgttttgagt tattgacaat agtgggagcq tctggcgctc tgatgcagag agtttagtqa aaacgatcca cgcatacacc catcgcacac ccccaacttq caacgcctcc actcggcttc aqacaaagac tgcaacccca tccgtcgcgt taagcatctc cggcggctcc ctggggcgac ttacactatg tacctccttt cgccatcgqa gtacgqgaag *cattgcatac aatacgtcaa *attataccqa tcatcgatga tccatggtat tgttcggaag cattcgttct ccggaggctg gtttctactg gtatctgacc acctggagga act accactq gtggctctcc gcagaaggac tggataagcg tggaatccga aatttccaat atcgtccaac accgaatccg tacgtgatcc cccgatggta gatggaagtt cccagaagat Cacaacgccg tttatggcga ggtgcatggg act qagaacc actgtctggg aatgatgggt 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 gtacttgatg atgaagttgg 24 /282 00 00 tggtggatgg gatggcactg taagtqatgc acagaatagc ttctttcacc tttgtaatgt ccgtggtatc gggacgcgat ggaqggggtt tgcggagggg gagagat gag at at cgacag caccccct ag acccctcccc cgccacacac cagaaaccca ctcccagata ctgactaatg ccttgacgca tgcgaagaga gagtacactt tggagatgcc atctaaacag tctacttcga cgcataagaa aacaacaacc tacttctgca a ga tat gat t gactgaagqc gacattgtgt ggattggggc cttcctacgg tggtttatta taagtataaa aacaaacacc cctaaacaac cacccacgag ccagcgcccc agcaaaatcc aaccatgtaa tgactggcgg aaggagcggc ga tgtta gt c gaataggact tctataagtt acaccaccaa agccctcaac cagactcacc ggaaataggt acccttactc tccgaacttc gaagaatcgc tcatagtaqt ttgcacaggt aattatctag atcacacgca catcctcatc tccatactct cccgcgt at a atcccagcca cccaagaaga gtgcaaqcca tgtgagatct ttaaattgga cgttcttggt cactaataca taaaccccat ctcaccaaac gcgcccccct tcgacagcgc tagcactaca tcaattcaaa 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3598 ataaatctaa tgtgcatacc tcaaagccgt agcccccata acaaccccca ccgccaac <210> <211> <212> <213> 14 2847 DNA Aspergillus niger <400> 14 cttttggctt gccatttctg gaagacacgg ccatctactg cccgagtcgt agtccaaagt ttggctaacg caatctaagg gacttgtcgg tccgtcagac actaaggcag ctgtcttggc gcggagatct gccatagcgg gtgatcttga gttaccttct cttctccatc gtcattggtc caggggcagc ctgaccgtca tatggcgtct acatccgcgc accagtgcta cctgccagtt gqtccagggc aattgcgaat tcgtcggttt ggactctgag ttgctagaga ctttcccttt gcggcccacc caatqcagag ggcagcgacg cat tgtgcca ccggaggccc ctaagatatc tcgtgatcgg aatctgctat tgtatgtctt atcctcacgg attcctggaa acatttttgc tgtatatcct ttgtctcgat aaccaacaat actccgtcga agctaaatta qgcagataag gacggaccct tacccttcag cccccacgqt ctactccgcg actttgcacc gcgacggacg gggacatcat tctgaagagc cacggatacc cgtgaggcgg gtccttggac gctcaaatgg gaccactgat ttgaatcgtg gcgcgatcgg cagttcagcc cgaatqagct gtaacatcgt gagtcggccg acacggattt ctccttccat atggtcgact gccggagtgc aacgcaggat gcccaactct gccggccaac aagacgcgat tgactggatg cggtggagcg tagccctgca Cttgtctctt gcctgtctcc ccggttggct ggacggacat cat qacggct tggatgatgg 120 180 240 300 360 420 480 540 600 660 720 780 840 /282 aggagttgat cgaggtcaat gaggagaggc ttgcaagtat aagaagagac tgctcgacca gcagaatggz tcttctccgz cgctgccctc gggcttcacc aggcatgtac ggctgccagc tcccgtcact gtaagcttcc ctcggacgag cgcgaccaag cggaqacgtg tgaagcagcc gggactggcc tacctgctga agtcccagct acgactttgg atagctccca ccaqctccag tgtccacctc cgaaatcgtc tggctacgtt caaggccgtt ctgctttggc cttgaagagc qgcttagatt ctacatgtgg ccgtacatac atatgtatcc aact ctcttqc gttctgggtc atcaaccaga gcccgtt ccc aagggtagtg gtcggaaagt ctgctcgggt ctcccttcct ctgagcggct taccgggata agcaagatca tttagctcca ccgatacaca ggactct ccc ctacatcgat gggttactgg cggcttcaqc tttactaact tccgcct act ttctcttgct gttccgggca ggtatccaga cagtacgtgg atccactgaa aaatgcatag ttgatgaagc atctcatggc *catcaaccaa *ttqacattct *tgtcctccgc ttgcccggcc tggccaagtt ccgtgaccac ccaccctcca gttcgggcaa cggagcagac acacttggga ctgtcactqt gctccgagtt tcaacactgg gtccagccca. cttttcgccg gactccaagt ggcttcagca qccattqctg agtgtataga acgagcaggt cgaccaaccc agtacatcaa gcaacagcgg tct tcaactc gtggagtcta cagacgaggg tcggtacata ttttggctat gagtccaaqg cqtggtcaaa cgtctctgcg tgccaacaag tggcggtacg gccccagaac tctggacttt atcgtgacta cggtcacgat cat ctcctac cggcggtgtc cgttcagaac tgagtcaatc aggcgcagac tgcagctgaa acaccggttc ccgacggcta gtaagaaccg caccggtacc ttctggcgct ccctgacttc ctacgctccc tctgggactg tgagggccct tgatctgctg tgatggtgat tgcaaatgtg gagtgcagga1 cttctttgtc atggtcgtct gcgccggctc acccgcacca qtgccccaga aatgacgagg gacaccggat acctggacta ctgtacacgc ggtgacggca accaccaaca acggccaatg ctacatcagc caccttcttc gcacgacgcc tat cacctac cagtatcggt cctt cat tta accctcatcc caggaqaqcg actgtcgtga atct cgactg tccatcctgg aagctgggat attgatccct gatgttgatt actgtatcta1 taaacacctg tggttctatc tcagcaaaac ctactcgcaa tcaacctgcc gcgtgaagga agtacctgac ctgcagatct gctgggtctt ctagctccag gctcggccag agcaggctgt acggcctttt cgggttgacc gacaccgtca cccggtgttt acggatgccg gacggcagct acacacaact tcctcgatga aggaagccgg ttggcgacta qcagctccac gtgatgtttt tcgccgctca cgacgatgaa tgatgatgac tgtgatgaat aaccagtagt 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 agtactttcc cacctatatc tactgcggtg cctcqtccgq cccaacatca ccccagaggt 2640 26 /282 qgccqcagag gaaggagtac ttaagaccca aacacctagt gagtcttata agatagctac tatcagttac aacacctctc tgacagatgt aataaatcac cqaaacacaa attcaactaa agtcggtaag taataataat atccacgcaa tgttaaacta tctctggtgt tgaaagatct ctcccctggc tgtgggagaa ctgtgtt 2700 2760 2820 2847 <210> <211> <212> <213> 2899 DNA Aspergillus niger <400> gcccaggtga atcgggacat cgtgcatcag tcaacatcta tagtcttatc ttggctgqggg atgatctaca aggtagatag aagtaqgcag gtgatccgac tgagactcaa cctgatcgtt gagcgataac ctgcgacctg tcttccctac Ctttgtctct at cat atccc caca gcat cc ggtgcctctg gttagcttca ataa cat cga iagaccggacz ggctaaccaE gctggatatc ggctatttca ggttggggcc cgqtgattta ggagtacgtg gacctgtccg gcaccgggaa cat cacqat a aggtagatat aagagcctag ccgtgacgat gcaggtcgct ccccagacct atcatcattt gctgggtagc gtgctgttgg gaagagcagc aagaagctcc cgcccatgtc iggaagcggat Igcatatagac -ggattacgca tattaggaca *aagtaccttq gcatatgtaa tctggctgtc cagctgttgg cctaaggcgg aggcctcagg aatgatggaa agaagatgta ccccttgcca ccgcaaccag Cctcttttcc tctattcata cgtttccgcc gctgtgcctc ttgtgagtgt agaaccattc cgcgctctgg aggtacggqa tcgaattcta aggcgaacag acgactgacg tagaactgta gctccagttg tgctgcctac ctagtttggt tcttacatca tagcaaggag agataggata cctggaagac aatgacgcag cgccgcccgg cttgctatcc cgtgcatcat1 gtcgcccatc cgccgaggtt ggtctttcac t aaagctgatt t cattttctaa ccggtaaatc ggggaccgtt cattgggtat acccacgtta gacggctacc ttggtagaca aaggcggttg tcacccgcgc accttccaga gctagatcag ctggcagcta Ccggqctggc ctccaagtca tccatctctt tcagtcgttt atgaagtcag -acaagctca a :gctttgttt t :cgtggtcta t tctacccgcg aagtatggga agctgtatta tccgctgggg ataccgccac cgagctt ccc ggtcaqcqat cgctagtttg tcggattcgc cagctctgaa gcttattgta caatcacctg caaccattgg cccgcatcac cttcatcgtt ggcccagtcc Ct ccttgct igcttaacaa ttttagcta *agtacacgc *gCCCgtCCa 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 gccagaagta catgggtatc tccacaaaga gctggtcgag gagaacccta tcaatgacat gagccgtcat gatgttctgg 1320 27 /282 tggacaactt gacccttcct ggttgtcctg cgcctgctac cagtgaattc cctgaagatt tggccttgcc ctccgtgaac gccggtcttt cttcggtggt caaggcttac ggagaacacc ggctgagatg aaccttctag act gcga caa ccatctcctc gcatggactt agtggtacag ttagttctgc gtagcttgat tgtttgcagc ttgaccttta acatqaatgc cagccgaagt cgctcttqgc tctctgctcg cgatcttcat cctgaacgca gccatagact gacactggca ctccacaaca gccatcaagt ggcgacctga tttgccttcg aagattgttc gccttctacc gtcgacaagg tgggaggttg ggtgtcattc atgtaagtcg caatgctcag gcgctcgtcc gtatgactac ccctgagccq cgtgtatgac gqqttgatgt ctatgatttt ggttgccgga tttgggcact aaatqgcgta ctggqccggc agccaaqcct gtctttgttt atccgatcg cagtgtatgq tctctgagat gctcgaacct agtatgattc acggctctgg aggtcaaggg gccggttcga ctcccttcta ttggagatac accactacac agcttgacgc tggacactgg aattcttcgg atcggtgcta ctgcccgatg accttggagg gttggtccct ctgqgcaaca ggtatctatg tgcagacgaa tagattctaq gagaatcttg aaccgtgtga gagtctcgcc tcttcatcac cat catcctc agataccgtc cgagctgggt ttgggttcct gtctgcctcc cagccttagc acaggacttc tggcattctc caacatgctt caacaaggag cggcgagctg cattgctctt tacctccctg attcctgggt agaagggctg ttactttcac tgcagggctc tqgccatttt gcgctgttgg atgcagctgk cacacgtgat ggatcttcaa actgtatgaa tqcagtcaca ccgcacaggc gctctcacca ccacgcctgc ttcttatggc act ccccccc tcgagcgaat agtacgtatc ggattcattt gctgaggcga ggcttgggtt gaccagggac ggtgacgagt atcaagattc gqcgatgatg attgctctgc tgaaaagaaa gaccggccag ccttgccggc ttqcgtcagt gggcgatgcg tctggccaag tgctgtcatt gttgtqaatg tggaaagccg atatgatagt ataaccagca cagqcgccaa cctcctccat ccttctattc tgcaactgct agaagttcaa gcagctctat acaagaatgg ctcaggacac ccaatgagcc atgacaccat tcctcgacga ccgtggcgac ccctccgtcg ttgctgagat ctactgacct tgctgctaac tacaccgttg cacaacttca gccttcatqg ttcctgcgca gccaagtaaa attgcttctt gttttcctca gtgatattat aacaccttaa accgcggtac acccaagcag ccaggctttc aaccgctctt 1380 1440 1500 1560 1620 1680 1340 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2899 <210> <211> <212> <213> 16 2-738 DNA Aspergillus niger 28 /282 <400> 16 gaggcatga aggggaggt a at cgct ca tat taaaaa gagaacaaa, a at tca cac agaagaCCt( Ctgacctgai ccaacgagac gcctgaatac ttatcqcgtc at cacccga c agtggatgat cttactagtt tggtggtttc cctccacttt caactacaag tcccaccaag cactgaaaag caccagcgat ggcgaccgtg agctgatctt cagatgtagg gcgatcttcg atctcctacg ggcggcgtag gcccaagqcg Ccaaagtccg gctgagctgt acctttggct gcatttctga ggcccgctac tccgcattct gcagcatatc gtctctgcgt c gaaaccagc a tcgtgtagt a aqcagaaqa a tacgggaca a cgacacgaa 3 Cgtaatgat( a gcaattcgg( aagatgacac I tgcqacgagt atcggcgccc tgggggcgac gaatgttatc gactagccac tctCttcttc gatcaattat cgctcaggca cctqgtccct cccatcggg gaggttggcg gggatcggaa tgggtacacc tctggtccaa actcgtccaa gagatggatc tcgtcaagaa aaggggacgg tgaaaacgcc tcacggccaa tcattgacca t gtaggactc a tagctgtct t ggagtcaga g aatctcagt t aatagccga g ataagcaat, 3 gaggagacgi 3 gcccgtcgci -gtcccggttc Iatctcgcgat Iatttcagggc Ictggaagag ctagtatttE tcgtcatttt cctccatcat ccaagtccta acactctcag gtcgggccca aggttccggc ccccggcgca cccattatga caaactcccc atcgagcacc ctccgcatca ccaagccgtt attgctcggt cgtcgagaac gctggatacc ggatctggtg g gcttcgqtg c tttgttcct g CCacccggt g atqgqggag, a actaacaag c ccaccaatai :caagctcga( a ccacgccact ztgggcctccz cagctgaaac ca gct gaaa c igqgggagaat igctgctagct ct cttcat ct ggctaccaaa Cgtgcacttg cagctccatc tatccggcag cgaagatgtg gaacctgaag aagacctaat tcaacccttc ttcaagacct gggagtgtgg qaqctggcag ctagcattca t atctgtaccg c acaacatgtc t agqgccggqc a agagagagtg 3 taaatcacat 3 tacaatgcca :gatcaccgga :aactgcccta Icgataagata caatcattca ggtcggctgc gacgtctcaa agggattcgg catacccatt atcaagctca atgcgcaagt caacagaccg ctggtgcgga cagaacgact c atgqaaacga g tatccgagaa c tggaaggtga a gcaccgacga c agaagatgtc c gcaacatcaa c actgactaga tacgatatgc Cgcccgggag gcgacctgac cacatcatga ttgatagtgg gcttgaaaga acagaaatCg agtcatgggc atcaatttgc cgagattgtc ttctgggtca tttaaaagcc cttcaaaact tccccaatct accgcttcca gtcgtzcgta agaagagcac -Cat gtat Ct ~cactggttc Jcgtcactga .aagacccat tcctggcaa gtCa a cat t agcacattc acggtacag cccaagtcg tcgttttac tact a cacc 120 180 240 300 360 420 480 540 600 660 7 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 atgatCCtgc aggatgacat tqggcggaca aagacggcag Ctgatgacga gtgaagaggt 29/I282 cctgtcgata aaqaccatta gtggacgatg gaagtacagg tttgccgtgg aagacgggct ggagacacat gatatcgaag ccgtccagcg atcatggttt cttttgagcc gttatcagat cagcccgccc cctaccataa aacgccccgg cccatccacg acagtcaagg accggtcggg acacgtgtga gctggatcta qtgaaaaqca atgtctatgg ttttqaagag ctcactaact cgaggagttg gatgatgtta ccgaagtatg gctctggttt cgtccttcca ccgccgcaaa caataggatt tccccacaac cttctggcta taacaccgcc ggccatttat tccgaccgat gttcgtggtg aggaatccaa tatttatgct ggattgcaga cgccagagcc tgtatttgca tacgcagtaa gaagcacaaa tttccacaac aagctgcccc tccaatgaga agccatqtct ttcaactcga attgctgata agtgcaattg acggcgcagg cagaaggagg agtcqtggtg gtaagtgcat tctttgatgt tgaagtcgga tgtcccgttt atagcagtgc ggaagccatc ctcagcgcca ttccagaaaa atgccaagcc ggacacaa cctccgcgac ccggtacgac acggcgccta ataagctacc acctggcgtt atatgaccat tgctgttggc cgggaacctg gtagacgagt ttttggttaa aatatagtac agtctcccaa tgaaacatgc cagcatgttc ccgcgaacac ggtaaatgga gctggccttg ttatgatcag cactgtgtcg ttcggaggcg ggacatcttg gttaaggggt cgctttggag ggctgaatct atcctagtgg tccgtacctt tcagagcttc catccctgct cagatccaac gaaagacatg 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2738 <210> 17 <211> 2349 <212> DNA <213> Aspergillus niger <400> 17 cgcgcactaa cct caagcct tgggccaagc tggaacgatg tgtcgtacta ccgtgtt tag caagggagga ggcttgccgg caatcttggc tcgtgcgggc ccctccacgt tgcggtcaga cgtcggacgt tctgqctgtt ttqcatgttc tccgcgggct ccttactag gggttcattg ttgcaaggaa cat gctggat attccaatat taaggccctg ccgtcccccc gccatcgttc gtccgcgcta ggctgaccgg tagaaacggg cggcctggac ttgcgctcca ggatagtacg accaaatctg tacctagcta tctttccccc tcagaagcaa ctaggaaagt ctagctggcc atccaacaat gaagaaaggg accagaatgt ctgctccact cccaaagcgc gttgccgctg tcctctcccc cgccccctgg ttttttccca gtgccagttg qaggggaaaa agatgatcac ctctgcgtag ctcgctcgac cagccagctt ctcccggcgc tctccactgg atcgggtggc cccggaqtat ggtaaggttc qggcgga tat taatgcaaca ggatgccaat cttttgcagt 120 180 240 300 360 420 480 540 600 /282 00 00 ccacaatcgt gccccgacgg agattaaact tcggaagagc agaggcctgg caagcatcgc tcttcatctt taccggctcc tcgcaaggag cgacaaggag tggtgccgtc tgtctctgct caagagacaa cgagaccgct cgatgcctgg cgagggtgac cgttgagaac tgacctttgc tgtggctttc ttccactgtc caccgagacc tgcatgagat aaaaaatgag ctgttgatgt catgctgaaa cgatctgaag gctctgtcga agatgcttcg gggtggaaat cgcggt at a ttccccgtat tgaacctttc ccgtcggacg atggaagag attccgccgt ctggttcgtt ttcgaagaaa ctcttcgcca gcccgcgccg atcctcaagc ctgatcqgcg ggatctagca tccgaggagt attctccaga tacgagtggt accatcaagg ctgaccactg gagaccaacg gctgacttcg ggcccctctg tccgtctctg atcggtcgct tgatgagcta ttttgaatga at gactgt cc atctgaagat tcataacttt att tgat cat atcgggtcgt cgttgggcqq tgcatccccg aagaggagca gaaaacatca tctggtgtct cttctcactc ccaattctcc ct gccgct ct ctggcaagcg tgaacggcac acggctacac gctccagtgg actgcgcctc ctggtgtcga a ccccqa cta tcactgtcga gccagt ccgt ccgagtgqat qctccgttac acgctaccgt gcgacagcgt tcaatgtctt tccggattga ttatacctac ctgcttatat cact agt gag gtaaaagctt ctttactaga ggatggt at c ggqcgttttt gttttaqtcg gtggtgtcat acttcatttg tttcttcttc ttccaccacc aaacgtcaaa gqctgctcct ccacagcaac ctccaacgag caaggtCa ct ctacggcggt cgcttgggtt cttctgctac cgcctacgac ggccaccagc cacccacacc cgtcgaggac cttcaccaat tatggacatt cactgtcacc cgagacgaag tctgatcttg ttttaagtag tgtagaagat atctcgcagc gtatqcatag atccccattc ggagaagtct ct gcagct at attttagttg cgtcggcgga caaaacgctc atccagcatc agccttgtca atgaagttct ctcactgaga cctccctaca gattacagct ggcgagttca ggctacggct gqtatcgacg gaggatggcc ttcaacgaca aagagcagcg ttcagcggca ttcgagtctg gctgaggcta gagcaggatg tacgtttaaa acaaaccctg ttqagttgtt aagaaatgga cttccagaaa tcggctgtgt cagacatctg gagtagagct cacaacatga ggttgctgct gcgggcctgg ttgcatgcta gagcataaat gcaagtct ct ataagttagc ctaccatcct agcgccgtgc tccctggttc ccaactgggc ctgtccccag actacaagaa qtgacacctg agacttccta tcaccatctc gtagcgccac acgtcgaggg gtgactctct ccagcgacgg gcaccgtcct tgcatctcta qggatgaatg aattccgttt tgagcgcgtg gctgtgctgc aagtgcattt tcgattattt tcagagcgtc acgaaagatc 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2349 31/282 <210> <211> <212> <213> 18 1495 DNA Aspergiilus niger <400> 18 tgattgtgca gacttcctca aagcaggaaa acagactgcg gacgccaaga caatgcgggg cattacaacc tcatcgcctt 00 atcgagcttg ctactcgcta ttctttcttg gtatttttgt gagtgtcgtc actcacggca atgagatctc agtacttgta ccaatatcgc aactcacat-g tctgatagcc tcgtccctac tgatgctgtt ccccgtcgag ttcatcggtg cggacgaccc ccgacgccca gacatcgtca ggagacgcag gctcaccgtg cgaggatqgc gagaagctgt ttcagaggga cacgcctcqg cctagcagca tggaagacat cggacgttat ctctgcgagt tgaggatcgc aatgtcacct qacgggcaag gaqgttgccg qcagcacagc gttccctagt catgtcccag cagttttqqt tattttgcat tagtgaatac gccgcataga ttttgggcat tcatcgaagg agacaacaat gaaaccccag ggagacacgg gccggcgaga aaagctgccc gattgacttt cttgctttgt agggatagct cagctacctg acgggctttg ttctocagco caccctcttt tttcgataaa tccccgtcat tacacattgg atgggtatct ggagggagct agaagaaaca tttgccctcc tcatcctgta tcttccatgt tcgcgctaat tctgaatgac ttatcggtgg atatgggcgc aaggagtgtt aagacacgat ttccaagacc ctggaccttg ttcgatgact agttqcttat gaaatccgcc gggtaagctt attcaaqtct cacattctca tgtccatcct tctcgatgac cat agcagca gatgtccgac cgacttgcca tctcagcccc agaaaccgat caccagcttg tcccgcgtca caaggctctt tttttcaatc tcctatctga ctgatgggtt ggtgtaagat gtqacgaagg caactggcct gtggcttgga ggctttcgtt catgggagat tgtctctgaa ccagtgtcca aatctagtga cctgcatctt tcacccatac tatgccaaga atgaggaact atcaaagqca ctgqtgctta cgt cca ccgq gcgcggatct gcactggcat tgcttggatg gtgactagct ttctcggagt gtactatatt atgatcgcat caccatcaat cttatctcgt gcctctttct ggccggtcgc gatcgcaaca tacggccccg acagatcagg taccattctc acgcctcata cagacggctc ccgttgcata cgcacggagg actattccgt gatccgggta gggctggccc acgaagattt ccactgatgc accagqcggg aggatataga ggagtgagca tqtgacattg tttttggcaa cacacctggc ttattactgg 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 tgttggattt gtgtagggat agaaccaata tagattaaat tctcacgcca tacat <210> 19 <211> 2501 1495 32/282 <212> DNA <213> Aspergillus niger <400> 19 gcgtcttcgq cactaaataa gaacggaggc ggaatttctg aggtqttcjaa gacattcgtg aagacaagaa ctgccgtctt tatgccttca cat gggctca tggtatcaac t tcagcgatg ggctcttagt ggctggcact gatatttgtg ctccactctc ggagcacaga ggcatggcaa ctttagccgc ggtgggcggc gatattcgca ttacgaccaa ccacgctgct caaacaactt gctaactgcc aggcgcattc tggccttgcc ctttctcgag icaagcggaag acacacggac attaaccctg accgcacacg ttcattttcc accgaaaccg aggaatgcct cctttgttgt tactccgcca aggcagggaa ccagaccttg gccactgcgt cctgatcact tat caaaatc tacgataccg tccttcttca tactatggaa tacctcacca gagaagtatc tcgtacgcag gccttttcct gtctatcgtg ctggaatata ttcttcggat atctacggct tgcgagtatc cctacgtatg ctggtcaatc ggaccccgca aaagctacgc attgccattg ttcagqaacc atgtggtttt atgcgtccgt atqccaggca gtaggcagac tctcactcac tcaatcatgg gaaccttctc caatagccgc aggccccctt ggttgcacaa tggagacgga gattgtagac ggttctgggt gggagtcgga gagaattcct actcgacccc ccaagcaggc ctgacatgga ggattcgtgc cat cgt ctcc gcatggttgc t tga cga tca ctggcgccga acttccaaag tcgaaattga gcggccagta tgaatatggg ggctgcccqt tgattgttat acccatttta gtctcctaga ggtctaccat caagaaggga cat tacacac catcggggct tggctggggt ccagcagaac atatgccacc tcagatccct cagcgatgaa tggcggatcg gatcgaattc ggctcccgta gctcgcggac cctgacgccg tgcattaact ggtggaagca caqcggatgg actttcggat gaccaactcc ttatggtatg tcccaagacg tgtcgccgaa gaccaactgc gcgccccgaa ggtcttgtcc tcacggctga gcaatttctg ggtagttatg atttggtaat agtgtccctt ttcctgcttt actcagtcac ctcaactccc gtatgaaaag attgaccata ttctatcagc atagcccagt aacgccatgg tcctatgaaa cttccgt act cagggcacgc cgcaaggagt caggtcaata accaactgct gaagatacag aacggtgatt gcgggaggta aacgggacta cgatgggccg gggcctcagg gccgcaqccc aacataacgg gcatgttgat ctqtatggca cttcgtacat ttgggtgcta gaaggccccg cgcagcccgt ttgctcactt tcatttcaca caccagccct acaacgcatc ctggcaaccc cctacctaac gaatcgcctg ctccacccga ttgctagtaa cgtggatcat acccagagac tgagcgcgta cqgcagatat ctacctcggt tcactqcagc ttqgaggtct caggaccgga cat ggccaa c acgcgtctca 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 33 /282 gccaattgac gcaatactgc ct cgcgat at agtggacaag gggatggacg at cat tgt cc gatcccagcc ct cggaa cat ct tca cat cc gtgatctggg gagcctggag cctacttact agatqatcaa aaagtcctgc tgtgactttt agcgaatggg cagtcggtgg ggactgctgc atccgcccgt attctgtcga tgtggggtgc tgctttgact gccttgttgc gggccagggg ccaggataaa tagaaaggta cgagaagcct atgcaggtgc ccaagccata ggttcttcca aataccagca ctccgtcgcc c caat g tt ta cagaagattt agaccaatga ttcaagcgac aatggctcga gtgtgtgggt gaagatagga cagggcgcgt cggaggtttt cgcttttccc cggcgatccc ggcgaacaac agaagtatgt gcgggcggat cttcagcgga cgcacctcaa ggacaccgtc gccgaccgtg atgttttqga gtgtaggtgt caaggatgac cacggcgaag ggatcaacgt ttttgggaga tcggccatca gatgggccgc aaccgqcagt gatgtcaacc ggagaattcg ggggtggagt tttggatacg gggaagttat cagaactcaa gggtgtgttt tgagtggatc gtagactcgt tgggttttag cttggacttg act cgctggc tccccgatgc aagagtttgg atccgtggcg ttacgagcgc tcatgcagaa cacgcggcat gccaatccag ggttgtgctg ctgggatgct accccaqatt cgtcacgtcc 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2501 <210> <211> <212> <213> 2660 DNA Aspergillus niger <400> agagtccgcc g tgag tag ga cggctagact gtcagaccat ccttggcggt cgcgcacctc ttcaattcga cggttaagtc ctgtgaccct gctcatttgc ttattgatta cgtagacaac gttggctgct ttgacaatgt atggagtata gccttgtttt ctatcaatag cgaggagtga tgacgcaacg cctctccgtg aacattgcaa tggagcctga agtgcagagg ttatattata atgaagctct gttgtaccgc ctaagaaagc gtgcttgagt cggtctagga tgcgagatag tgagttgtgc gtctcaaagg tctgtctagc atcagtcctt tcaattgccg ttcatcagca tcctatcttc caatagctct agcaagaacc atgctgagcc gctttcacgc accattcaag cagagagtcg gaccagcgcg ggggtctcac atcaccccaa tcatttttgc aaaggtgttc tcagctgtac tccgccaatc tgcactcggc gctgataacc ccctccccca tggtaaacgg attcaacggc gaccggagtc tgttccttat ctcttgcatg atcctatcgg ccagctcagc gggcgggtca tacttgactt ttccatcgcc gcaacggctt ccccaagatc gtgtttatag acccgctggg tacaagtcaa tcacaggcat ttaagccgcg ttcggctgca aatagtcctc gctcggcctt gccttggaca cctatcatca ggtagttttt cgacgggggt ccccaactca 120 180 240 300 360 420 480 540 600 660 720 780 34/282 tcatcatcag ggaagaaaag tagcacatct attactgaag tatccgccga gacaacatgg tccactggta tcgggtgcag agtatcattg gacagcatca agtggaaccg cggggcaacq cttgqttcgc cttcaacagg attgggatta act gaggtaa caaagtattg cgtccgcaag gcaacaagag tggagcatgc gtccttcatg cttatatgtg aaccaatact ttgcctatat tggactttat taacaaataa gataagataa aagacggtca cggtctgttt t aagctcaccc t gagaagttct tgggacttaa cactgatcgc aacgaaacac cgatgaagca agcaaaacct ttgagtccgc cagagtacgg ctcggatccc atcttttcct tgactatact cttccaacac aagccatatt atatgactgg tggttgacta ggt cact ccc tggtattggc caaatatggc gatccacacg gaggttgaca attttacgtt ttcaggtttc accacagatt a atatgttgac a aacacgtgtg a acgaaggaga t ftccgccggq g :ctccttgtt a :tcatactac a tgatcgagtt aactggtata tctgcgaatg tgggttctac tgcqgagaaq caacaaattt aaagtggcta Cgccactgtg aggccagact cccctccatc cgaaqctttg aatcgaattc ctctcaatat ttatacccag cgt tgat gag gctttccttc tacatcgaaa tatcccgcaq actgatgaca cttggcttcg 3taaccgggt -tatqtcggt1 ~tggaatagat latactattg 'ctcttatgg g .Cctactata c cgatcactt c ccactccct t taatattct a ggctccttat gcaacattcc ttccattagg ccaacgttgc gtggttcccc acctcatttc tacagtaggg gagcagttcg aacaaaactg ctagctgcac cgtggtctgc cactgqtact aagagagata ggagctctgg ggactgacac tttgtgagac ccagatgtgg ctatggcgac gcatccggta cttacqaqct ctagcagata :tattgtggc :gtctgaggc ;ctttggtga ~taccggcaa jtggcatgat :ccgattgag t :cactggctt c tgcccttca g cataacttg c Cagacgagat ccattttatt atqgcgtgaa atqctggtag ttctgcgqggg acactcgcta tttcggatgt Ctcactcatg ttgtcctggg ctggtgccga tgcagtcaga cggcagagga agcgagacat acgccggtcg aattcctcaa atataactaa ctacgcctgt ggaatccgaa tctaagcttc ggcctttgct attctggcta attagacaag ccaagtgttg :tcaagaata cagactctaa c ~ataqtctqc a :cacactagc c :aatcttcga g ~atcagatcc t :ttggactga a gggttaccga actgtcacaa cttcatcgat Ctatgttcac tctctccaag ctataggtcg cattgagcag gggccaattc cgcacatcag tgatgacgga cgccattgtc aggtlggtatg caaggcgatg tcaagaagcc agatgtcact cgattqcgqt tcggaccaca atggaaaaca gatcatatgc caattctagt actagtgagg attacagagt Icaaggaacc ;gcctatggc actagcacc ~gaatggccc .tgaaacaga rtcattcctg gaacggaga ttggcqata 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 25 2580 35/282 ttccgtcgqt cgctcctatc tatcgcctac gtcaccagcg gtgcccctcc aaggaagacc 2640 ccaccatcag accttgqatc 2660 <210> 21 <211> 2047 <212> DNA <213>~ Aspergillus niger <400> 21 ccgaqctata atgataagct g t ttatct gt gcggggaaac ctatttagat tacaatctaa act act acgt agtccaacaa atatccgccc tatagcaagt gctctcgacg gtcaacggca gatatggcaa ggtcgaattg aaggaga at a tcqccaccac acgcaaaaaa tcgctgggcc ttcaccagac acaccccagt ggaccctcag tggtccctag a cat tct gcc acagcggtaq caaatqcgca tccagcaatg tat ctct ctc gtatactacc atatttaggc gttgaggaga cttttgctag aaaataacga ctttgcacca tctcgtacga gtgtcatcgt ccaatttacc gcctcacgaa cgcttaatgt ttactatctt ttttctctqc ttatcaatac tcgttatcga cgcttgaaat cacccaacta aaccacagcg acggcgtatc agatgatcct acatgatttt tacaaaaatg gcggccaagc ggagtaaact a at caaaca c atgacaagta qatttgaatc gcttgcattg tgggaaactg aatggtccaa caaagtccat cagcgaattt tcgatacctg gctgttcacc aactgttgca ggagctgttc ttattatacg ccccggcagc gaccgtaacg gacatctacc cgaccgcaca tccacaacca aggt cat qca caacaacggc cacaaacttc gacagagtta gatatgcaaa gtatgctctt cccgagatgg tcaatggatg agaaagcagc gcagtggcct gtatatggct aatgttagcg cccatcgagc gccttqqgca caggaaqaca acggtaqctg acttatatac acgcatacaa acgtatgatg acatacctct ggacgtgccc ttcttcaacc gccgtacaag gtgcgcggca ggtctattct a cat atgcag aatgccaggt catttcaacg ccgattttag cgccgaaacc tqactccgaa acagaaacac tcqcacattt cagttggtat caccagaatc catatacaca cagggtctgt agagaaatct ccaccctgga ctttacggga cggactttgc gcygtttcgc aacgcattaa acttagatct tggatgatct gcgqgaatat aatttcagat cagttcacga ccactgtqcg gccaacggat ttccggggga ataaacatga tacgcattcg acaaaaqtaa cgcagcagac cgagacctgg Cat catqaaa tgtctttgct cgtcggcatg tgctgccaac taccctggtg ctacgccgat tacaqtctac acttgacgct gacgaatggg ttctgatcca agcaattttg caactttatg tatttatgac cgaaggctct cgcagccctc cgagaacgca cgatacagcg cctttctcga tgctcgtagt 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 36 /282 ttaqggtttg agtcacactg ttgcatttta gaggctattg taatggttga tatgtacacg gaatccggat acaaatattc cggaagaccg aatctaccat tgcaggg agttggatca gatttactgg gtaaccgggt qgtattgggt gcggagqacg aggaatgtat aattttgtta accattcaat atcctgtcag gaatcaaccc gtattctact gactacgttg goat ccgtc tgggaagagc taccagatgg tcgaatgcaa aggcaaatcc atggcatgtt ggaattagtc cgagccctaa gcgggaccga gtgatggata agggcatggt ttggggttgg gatcctggat atacctcata agaaatttct atcatccatt aaccctctcc ataatccgaa tggcgaqttt qgacgtataa ct agcaata c atgttgcgtt tcattccttc tattacagaa aaaggttcac ctcataaaag aataaatgca aagatccagt gcaaactgcg cgccttttgg tat tgtgaga tgctctgttg gatacacttg tccgcagtat taccataaac accctcgatc gcatgaaaga ctggtgacag 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2047 <210> <211> <212> <213> 22 2730 DNA Aspergillus niger <400> 22 tggccacgcc cttccttacc aagtctggcg ttcctctggc acgttat ccc aagtqcaagg tgggaccgtt taccccggtc atcattccgc CCtttttctg cttgcccggt ccggaacggt aggtggatcc ccaaccgcca gcgcgttgat agggttcctg atcctot tat oat ctttcac cgcgtctgga cttgaccttc cga oat tgtg cccagttggo tootoogcto agccgccgcc ggggagacca agcccgtcct gcccccgagg ccgcttagca acagaacaat gcggactgtg ggaggtcqgt ggacgaattc gctctctcta cctctcttcc cagoggctct tctgttcctg ctgotoatta taaatttcga cgtcttcggc gccgtattac cttccattcc tggtgtcagc ggcccttgct cotat ata ct ggaaatcttt atctggttga ccgta togc gccaatttgt tccactctct cctttccccc tgtgctagag aaccaggttc cot ccgcccc tgactccttg aatatctact aagtacccat ctccatggcg caaatcggoc gaagatgcat gacttattgc tcttctggca acggtggtcc tgaaggacaa tgttcgtcga cctcagctt tttcaaa tot gtottaaoto cotccogqto oaaggtaaog agogogacto act aotaota cgcotaotga tcctggttgc goagactatt gccgggtaag otocacqgog ctaccagaat cggatgtagt tgaaaoottg tcagccagtc ctotoaaooa cttgacotto otacocc ototccgoog ggtaagogaa oaagtccgot ttactattac tggtctcott tctcgacgct atgttoacto ottogotgto agcoatattg ogocatattg tccatggacg acotataatg ggaaocgggt 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 37 /282 tcagttatgt caacacggac agctatcttc atqagctcga tgagatgtcg gctcagttca 00 ttgtctttct gcaatcacct agatctacat tccaggaacg tattgattgg cat atgaaga agtcagtctg agaaggt cat atgacatccg aggacgtgaa agaagaagtc agtccccgcc ttttcagcgg acatgaagtg acgactggag acqtgctcat acatgctaga cgcgcattga cggcggagga caggcgaagc ggcgcagccg gctctgttct atttcgacga ccgtgggcga gaqccggggg gtaggtgtat gacgtgcctc acatttagac tcccgtctat ggaagagtgg atgctgccct tgccggcgag gaacaagaac caatggttgg aggccttatc taagtccagg gaatgctctg ccttcgtgac gccctatctg tggctgggtg ctcggttcaa agacaaggac gaacggaggc tttcgaaggc ctacaacgca tcgcttcatq cggcgagaag gcaggagaag cgttctcctc ccggcgtcac cgagcggttc ggcggagctc ggacagcgac cagtcataat ggcttgcttg cttatatgtg atgaacaaag aagccaacag ttcagattat agtcctgcac tcttacgccg gttcaaggga atttctccta aaggaaggca ctggaaactg ttggataaga accaccgatg cagcgggaag gagtgttcag ctacttcccg ctgatttgca acgggtttcg gagccgqcqg agccatatgg aatgtcgata ctgccccaqa gagaggatca gtcgtcatta cagggatacc cacaacaagc gatgaccttc gaggatgata ctatcctagt gggtctttgc catt tat cat tttatgaccg tct cat ccac ttccggagta cttcacggat gtcagcatat agaccatcgc atgaacagta gccggaccgc gcaaqaacaa cggtcgaaga catgcggtat atqtqgttaa gtgcagtgag gcttgctgga accatgttgg agacctcacc gtatctatca ttccctacga tcgcgagcat cgtcqqtggg aggagacgga tcggtgtatt ggggcgtctg gcacgggagg attctccaga tttcacgaca tcatctttgg cttttgtttt tttatctagc cttcctgata tgaacgcgat tctqttctaa tccatacatc ttcgtggaat catgtcctac gaaggaactc ggtccacctc caacaaatgt gaactggccc agcgcttaac cagcgctttc atcgggactt aacggaacag tggcgtctgg atatgccaga ccttcctcgt cggaggcagc cggccat ccc atggaaagcc agtttggggc gcataaggac cgcagacgtc cctcgaaaga gcattctcaa ttgggtaaac tgttttcttg tggctgcctg cat agccagg gatgtatgct cat ctgcgac gccaaagcca ctaaaaggcc ttgccctacg gaagttttac aacgactgcg ctcaacatgt accgacctgg atcaatccgg aatccgcaaa caaatcctcc ctcatcaata gctcctcqac aacctgactt cagagccggg cccgccgact aacagcaccg tacgccaagt ttcttcatct atgagcggaa gaagcggggq gaacactacg caggcct ccc ttgtqatggt gccacgaaag gcatcattta cggaaattcc 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2730 38 /282 <210> <211> <212> <213> 23 2660 DNA Aspergillus niger <400> 23 act ttattgc ataatttgct aagtacgcta cccatcttta aagttcaatg atcaggttcg gctgaacgtc tctgatttca aactcaatct tgctgcgacc caagcgtatg gatagcccac ggggtcgatc acctaagata ttcctccgaa tgcacccgtc ttcctgagga attcagggtt cgaagaagag gataaagaac tat ctcgtcg ccctgtctac gtccctctag gaactccctg tacatgaacg tact ttgcct caagcgaatg agactcaact ttgcacccaa gctttaataa gatctggtcc acggaggaat actcttccgc cctgcagtga gaacgaagtc agagcccagt tat tacaccg ttggtggaaa cctatcgatg ggcgaacctt cagggattct atcaacgaat ttaaattgga gaccaaccag attgccgccq tttcgcattt gcaatgctag tcataactac gagcccttct cctacccctt agcttgaaac ttccaccaag acttcgactt gattgctcgg tctgtaaaga ctccaatcat gtcgctagaa tcttctggtt tgtcaaagct caqttgcggc gggctgccgc cgagcaacac gccatqaact gcttacccga acagcaacaa cagacgacct ttcaggaaaa attcttgggt ggtatqcact tcggaaccgg attttctcga tcatgaccgg acaagaacga tacccctata ttatgacgcc cgtcaagcag cacctacgaa cggcatccaa t c ttat tt ct tgccatctta agacttctcc gacgattgga tat cggagta gggtacaaga tgttggctga tgcacttctg tcatttttcc ttccgactac ctattcgtcg tgtgcacttc tggatctcga taccatttac tggcaggttc caatttgacg ctgtacattt attttccgtt ctt ct t tga a tgagagctac caccacgcgt agcttagttg tgcatcggcc cacgcttcac gaatgcggct cccccaaaat gcaacgcgtt ccagggatcg aaactccaaa actatcggaa aatgagccca ttgacacgat cttcgatccc ctgatcaacg aaacgtcatc cgattcttca ctgacatgtg gatgttgggg tccctqtttt ctcaatggag acatggcagc aacatgctat tatgagacta ggaaatgtta aagtttgaag gccggtcgct ttcaatctga act gaaactg aatgggacta tat tca act t acaagqccta acatgaacta tggccagtta gcaagccgaa gtagaacaga aatataatct acccctggcc ccccttggcc ggatgatgtt gcgcaggagc cgacgtaccg ataataggac gtcatccctg agatgtactc atatcttcca ggccaggctg ctggtaccta ggtacgcttc atgtgaataa cagccaccaa atctatacgg atgttcccta gcggtacgag act ttttaac catccaggcc caatcagtcc cttcgatgag ctccqagtgc 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 39 /282 gacatctata acatgatcta ctacgaagcc tataacccga acccatqctt caatccctac cgcgtcattg tacgagcctg cccatggatg gacccgggtc cgtgttattg at caccaacg cagtccgcac tttgaggccc cattatgagc gatcaggqcc tagtctcccg tttattgata tggtttttaa atttttctat aattcaaatt cgcgagaaac taatqaagat cagtaatata atgagtgtcc cgcccaccac tggaatggga cggagcagca aggcgaccaa gcaccctcct ctgccacacc aggagggata gcggtttgat gtgtctcgta ccttagatat gtttcagtqa tgctgcctcc ctcaacttaa gatatttatt ttgttcctca ggagattatg tatctataat acttctctgg atacttcaac gctctgcagc aggggatgac ccgcgtgctc cgccatccag gatcgatatt tggagggctg gtgggcggag tcgccatctg aattgatatc attttgttac ttttaccgta ctttgtattg ggccttttat tcatactata cggattgcgc gacgtcctgg cgtatcgatg tacgacctcg tcacccaacc attgccaacg aatatgacct cagatgcccg gatggccctc acatatcagt cagtggctgt acactgtaat ttccagtaac gctacggcta ccccctggat tggcagcata tttatcccca acttcataat gctggccgac tcaagaaggc tcttcqctgg ccaccgaggg gtgactggga ggaacgqcca atctccagtg agggggttat cggggcataa tggggcaagt gttccctcca aactctatta tgactacata cctgactaca atatctttct cagctgatgc caaacatcgt aqacttggca cctgcacgcc aggcgacgct tgtcctcccg ctacctgatt gctgggcttc gqttgagatt gggtgtacaa gcaggctcag tgagattctt aaaagcttca tggcatt ccc taacqgactg gaaaataaat cat ataagca cgtgattcgg ataagtgtgt 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 26.40 2660 <210> 24 <211> 2800 <212> DNA <213> Aspergillus niger <400> 24 aatgccgaag cttgacctga tacgacttca cgctacaggc ccgcagtttc cgcttgaatt cttcccacga ggtctctttc cgagggcagc tctcctctcc catagctgtc cgcgagcttc tcctattcgc qcatggcccc gccagagatg tgctattccc cgccctcgag ttcccgacaa gttctgagag tgtactcaga caatcatatg tcgctgcact acatcatcgt taggcagcat aggtatcgtc cccgcat tag cgctgcaaca tcattgqtac tttctgcaag gttactttgt gttccctcca ggaactggca accgacaatc gaaatgagca tcattgggat ctcttcgcta gtcccatcac gtcagtggct tgtgctacgt cccgcacata gttatcatca tcgcattcct catgcttggt cctcqttgca cttqccgcqt gagaagcctg cgtcctagcg aagcccccga 120 180 240 300 360 420 480 /282 cacccccatc ccctt cat ca tgcacqgata atgaacatcg gactatcagt ggctgatttg atct gggcga ttttctttgt atggtggccc qgcagcctgg ttctgtgqta taacctattt accgctacgt cagatctttg tatgttcctt aaaggtgagt ctaggtgcac cctgttgttc gcggaactag gtcttcccag gatgtttatg gaaatcaacg tat ctccctg gctcctaaca ggtcccgagc atcgaaggca aacggcaccc gcccccagca gagaacggct ggtcttatgt gataggctcg gtatgctgtt atgcttcagc cgaagcgttc tcttgaacaa cttccgtcgg gatgtattcc cttccagccc tggttgcaqt aacctaccag agtgtgatat tttgtagggt ccgaggagga qgatcaaaaa acatatccgc tatacttcac tggcatatga cctttgtcca agagcatcca cat ccggtgt acatcgttaa agatgtgccc cgggcgccag tcacctggtc aggagggcga ccaaccqagt ttctctcqat cccccatcaa atgacccaca gggctgagac gtgttcqtgc tcgcagtctg tgctaaacat cgctaacgcc caagactaag acagcttacc ggcttggtcc actattggcg tcccttgagg cctgttgaga tactggatcg tgaccaacct gattgctgaa cttcaagatc tgctttccta caaagtaatc tccctgtatt gaagaacaat tgagcaatgt ccagccgcca taacgccgtc cattctctqq catctacttt cgagtgctcg ctactcggcc tctqatcggt ccagaacatg catcgacatc aggtggtcag cttccagagc acgcctgtcc ttgtcgacgg ggtcgatttg gtgaaacact cgtatgtatc gcgtggaaag ct at tgagaa agcctgtgga cctttctcca acccatactc ctagttgagt gtgggaacgg gactttqtga tatqttactg gatcagaatg tttaactagq ggtcagtttg gccctcttca ggatacaaqg aaggctatga ctgqatccca gacgttcttg qaccgcgctg gtggagagcg aaccccatcg aacggtgatt acatggaatg cctgacctga ggtgtcatqg ggacacatgc actggcccct ctgtcctagc gccaaaaagc cgttqaagat tcagttcgat cctgcctgat gggcaacqtg tgagatcacc ggagaatggt gtgggtgaat ttacatgggc gattctctct agttcttcaa gagaaagtta atacagaaca gcttgtactg actacgtgca atttcaatgc atttcatcga actggagcga acccgtgctt gattccccac atgttaagcg tctttgtcgg agcatgtctt atgacatggt gaaagcttgg tgtacaatga gcatccagca agccccaatt cccccaaagg cgtctcgctg tcgcgacgcc ccctgtcgag attgaacgat gttcacttcg tcacggtccc atctggctga agattcgtgt ctcaccaatg ggtatcgacc gggtgtccca gaactggcag tgcgqgccgt cttcaaccta attgtactat ggaggaagca aagctttttg ccagtatcta tcccacctgt caacccctac cgaagtcgac tgccatqcac gggcgacggc gccccaggtc cat cct ta cc attcgacacg agtgttcatt ctatgagcgt ccaacccaqa 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 41/282 gt gtcat acc gctaccacgg atgcgaatgt actggcctac ctaacaaqca tctacttatg gta cat taaa tgaacaattg acgcagtatc gtcaccttga gggacgatgt acatgaattg ttaccctcac taacgtagct acgctatttg ctcaatgtgc tccccqagag ctccactaat qtggctgctt cacgatgata cttttactg ttcccctatc gatttgaagc act gct aact cttgcccagg agagagagag gccgtaacac ggccggcggg gtcataagtt cagtctctaa ttttcaacct agagcataac cgggtttaat aaacgatatt agcgagcggt aggaaatgga ataccctgta atgatctgta agcaaaattc gaagaccgga acactctacc cctgaagctg tgacttatat aaatacttag aggcgggtag gatacgttgt atagtagagt agaattgtaa cctcggcact cagtccaatc qatctgaaaa caagtcagtc 2340 2400 2460 2520 2580 2640 2700 2760 2800 <210> <211> <212> <213> 2165 DNA Aspergillus niger <400> gaatcaggat cggaqacatg ctgtgtagaa tgctttgacc agtgtgagca aacaggcaga cggcacatcc aggaaaacag ggcattcctt atgcccattg actttgcaga cgctaggatq tcattagctt tgctcaatcg gtaaagaccg ccttatgtga atcgccgagt qgaggcccga gtcggagcta gtcagaccct aatttqgggc ccatgcttac agagaaatgc gtcttggact acgcccggtc ttgcccatgg agcqcaggag actgggtatg cgacctatta tggacactgg acaatctatg tgggcacaca ccgataagct caacgactag cggccatcaa ccgccgaaca tccggctgct cgaccgaatt ggcgqgaata ttggatccag tgagtcactt actattgcct tgccttqcct tgtgcttctt agtcaagatg cctgtctctc cgcccagtcc ttaagctata cqcagtcaac cagcagcgac caccccttat cctcaacgat cacgatcggc taaacgtggg gccgtccaaa cgttcgttgt ggtcgatgat tagcctggcc cttgggggcc tgcaacttac aaaggtgcgg cataaacgcg ttgcagaaac cggccgtqaa ctgacgttag ctctgggtga ggcttqtaca acatatgcgg aacacaacaa tgaaccgttt gtcacgatag gaatggctcc gactggctat gttgaagctg aatttaacct gttataacga cgctaattcc acgggcctgc gagattctac gtatagatca gaacacctgc acaccggcaa atgccagcga acggcacaaa tcgataatat gtccatgaat gtcqcttgta acgcagcctt accagtgcaa acatgagagg ccccagactg gtctgtgaac tcttgcggcg cgtcgttcgt ggtcggtgtg tgctgacaat gcaaaaggta ctcaacttac atcgtct act cctttacggt qcagtttggg gatcgtcgct 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 42 /282 00 00 gactaggtct actataggcg ggatcgccgg cgtcqgttac aagatttcga cctaccaagc cgagcatgac taagtctgct tttcqgaggt tgtgtatqgc ct ccaact cc caccatgacg ctacgacaag tgtaacatac cgcaacggag gggcgtgaac gaacaacqaa aatcggaacg tgcaactgga aataactgct ggctgaagcc gaacctgctc ctactcaaat gacaaagtct gcgtacagca gtcaatacag aaatactact aqtaqcttca gcactgccca acatacgaca agtttctccg ccggggtggc ctgctcggtg atctctctcg ggaacgtctg aatggactga acagccacag acgagtactt ccaggacttg agatatcacg acgccaacct tatggctaga ccaagtacaa ccctcgccat ccgacagtct gcgacctggt tggcctacat gggcaacgat ccqacaacac atacattcct ccaataccaa ctgtgccagg tctcgtctg caaccggctc cctcggaggg cgggtatcgg acgagactct ccctcaggcc tagtttggag gggcgatctg cgcccttacg ccccctctct caacaaggtc cgactgcgac caccgtgagc qtgtgtcttg gcgcagtgcg tttcaatcca agccacaccg caccgcagtg aaccggcact cgctgcggcg cctacttctc aatgtaataa ctcgtcgaca gcgtcgactg cagactcttc gagctcagcg gtqt ca ctcg tacgatgcgc actagagagg atqagtgagc ggcctcgtgc tacgtcgtgt ggcgacgatg gttccctctg cccacgctgt ggctctagcg caagctacqa gctctgtaac tgtggtatac gcggtgccat gctccctcct cgatcattcc ttgcgaccga atactggcac tcaacgcaac cggattacaa tgattatccc ctagccagcc atgatctcga atatcctcga ctqtctcttc cgggtgtcac gtggttcgtc gcaacccgat gcgattgtac aataacccca 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 atatctacat ttccttaacc gtaaactgca tactctacac caaatccacc accaaaatac atacc 2160 2165 <210> 26 <211> 2800 <212> DNA <213> Aspergillus niger <400> 26 gcccagccaa tcataagaaa cc gccaaacaac cggtttgttg ga aaacaaagca ggtaacacaa ag agccqgacag gatggcgcta gt tcagcgtccc tcccagcccc cg gcagcggcag taatqatagt cc tactacttat ctctcctcgt cc( cggtcctg cgccctgc atataata gtcacctc at acagt a tgccggtg ctttcact gcaaggtctt ggtacactga cggcggaatg cagcttcggc atggtatgca aataataccc ttccctttgc ggcggggatg aatcttgggc ataggatatc taccctcgca catcgcagtc cataacaaac cgtcttcaat gtgcaagcca tgttcgacaa cctgtcgatc gcggacccaa ttaatcqcct aaataaataa cccct cat ct 120 180 240 300 360 420 43 /282 tggtctcttc tccctcqcgg tccggcgtcc gtgattcctt cattcgcttg gqatatgtcc gaagcgcatg cgccggtgtc caaggccaat tcgtcgtctg gatccagccc gcccaagcac ctgcgactcc ggccgat ccc gtatgccgat cagcgtcgtc aqccaacctc cagcaccggc cagcaacgag cccacaagtc attccatttt gtcccctacg gtaatcttct aaccgcacgc gcaacctcca ctctggcccc ggcaacaagt ca gggcgt ca tgctccgcgc ggcagccttt tgttgtcgct ccaatggtga cgaatactac caaatcgccc acccccggac ttgctcccca cacaa tat cc gccctgctgg cgcaccctgc accacccgct gccgatgaga at cat cacac aagtccggca ctcgagaggt caattcaacg gacctgcagt ggacgcggcg ccctaccttg atctctacct acatccctca cccgcaccgt ccagcggcga acttccctcc agacctcccc gcccctccta tctcggggct actacgctgt cgacgttcag caccatgctg gct ccct tog gttatagacc caggctggag ttcagcagca acgccgacta gcgagactgc aggtcgacgc atgccgactt aatactccat ttggccagat cattcctcac cgcactgtct gcaagatcgg tcgagcagca gcggcctcaa acatcctggg aactagt ccc acttccttca cctacggtga cctctctcaa ctqcaacctc ctccggcgtc tcaattcccc cgagcaagcc ccaacacgcc tttcaacgcc ttacgacaag tggcgtcatc tcgtctctcc cctgtagccg ccaattcttc atacgccaac tgatgtcgct tggaaaqcat cgtcgactca cgactgggtc caagtggtat ccccgacgcc ccagcccaac cgcagccacc gaaqcagctg ctttgccagc cctggct ccc cgatcagctt cgtcagcgct cgacctgagc gggaatcctc agacgaacag ccaaactaac tacgcccaac ggcgccgcct gcctcctgcc gtctccttct gccgtgcaaa tccggccgcg ggcatgcttg gcgttgttga ttagccaggg cggagatctt attttgagcc aatcctcaag ggtttcgaac ttccgcaccc gtccgcgact aagttccata gtcagcgacg ctggtctcgc cgtgccacca ctggcccaga tacaacatcg taccttgagg aatgccatcg tcatcgagtg cccgtcccca tcccccgacc aagcttaaca gtatgcacct aacaccaaca t cggcaqccg gcctcaccaa cctgggtaac cctccqgcgq cctacctcac ccttccccga gccagttcga acgatgcgag agcagccgta cgaaaagcta acatactgac gcaacgaggt aagccgtgat acgatgagat ggctggaatc ccaccgtaaa ccaaqcatat acatcaacat tgcgcagcaa acacctccca gtgactacca aatacgcccg gccaqaactt acagcggcga tcaccgagta ccaacgacaa act ccgacct cacctgaccc gactatcccc cggcgtctct cgacggcacc ctccgtcggc cttctccgac .aagcacctg cgtctccqcg cqggacgagt actgagggcc 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 gggttgcctg tgatggggtt cttgaatccg ttcctgtatg gtgtcggaag tgagaagggt 44 /282 gcgttgaatg ggcacgccta gatcctgtgt gaggagggtg ttaggtgaat tggaagaaat gatgacttgt t at aaaata t tatctgtatc gggcacacca atattgtgaa atggtagtcc cggggttggg gtaattaagt tqtgtggata gtct a atgag ctttgtactg atacaaaggt ggtagcagat ccagtgccaa cggcgggagt tgttgtgccg aacgccqgat gtgagatggg attttcatac tgtgatttgt tat aacgaaa taacccatgc aagtgtatgc acagctccat gtgggttgtg tttgctaqtt tttgcgaagt gggaaaggga ataattaagt ttacttatgt tgattatttg agtcgtaacc aatctatctt cttgatgcgg atgggaggaa ggaatgccac tgaaaggggt ttttcttttc ctgcattggc at at tgagt a agtggagggt cat aatgcaa tgttgatgat tcggttcggg gaccgggtgg ggcgttgggt gatgtgaata agtgataacc atggaatgta attaaagaac agctctactc gcaatcaagc 2280 2340 2400 2460 2520 2580 2640 2700 2760 2800 <210> <211> <212> <213> 27 2 660 DNA Aspergillus niger (400> 27 ggagacagaa caagttcatc cgaaataaat gtagacttgg gatgtcaact ctaacgtttt ttgcatgtgg a gtct cca ct Ct tctacacc cgcaacacta tagtcaacgc gtttgaatcc gatttcgaca agtctatact tcgccgtctc tacatggaat gcttagattq gatttatgac taaacattgc ctcaaaacac gctgaaacag tatgagacca tcagcagtgt tcttcatctt gagaatcatg acagtctcaa cactaacagc ttggcgagtc tctggttctt atatgcttcg tgatgctcaa ggaggatcgg tatttgcggg tatcgat ccc agcattccac qtacctcttg ttggcggcat gtttgtgata cacttcacca tggctct tt c tacttcaaca gctagaattc ctatgcgggc tccatcttct cacggctaat caacgacaag ccaggtctgt catqagccct ccccttcgta agcqttcata gttatttttc ctagcttgaa gccaagacat atccactctc tcgtgtgcag acaaaaccaa gtcgtcaatg tacctaccca gatcctgatg aaacagatca gagctcgcgt atataggccg cacgtagtgt tattagt cat tgatgtcaat atatagtagg tggtactcaa cggcagtagt tcactgctca tat cctgctq aggtatacca gctctgctat acacgccttc cgtctgatga ccgtctggct tccgtaatgc cgatagaaca gctatagacc aattcttcct gtctcaatcc aaggtcgccc tat gaccagt tcctgcagag cttctagttt ccacttggag cat cqcgtca tccttttgtc tggaatctcg ggtatgctta gaatggcggc 120 180 240 300 360 420 480 540 600 660 720 780 840 900 ccaggatgca gctctctggc aggcatcatg ctcgagaacg gcccctttct atggcaacct 45/282 ggtacctacc attgatcagc gatgtagcca aatcgaaaga tcgcagatgc gatccctaca gcttactcct gctccctctt gtggctacac cagtgcccta tcaacccatg tcggcggccc aagccatcaa ccaacgqact agaccaacaa ccctgatcag tggagccgtt atacagagcg ctcagtatgc gcggcat at c ccggagacag tgcagacaat ttqacttttc tatcgcaatc tat tgccgga cagtagcgca cgggaattcc tctaagattc ttttgtatag <210> 28 gacccgtgcg ctgctggaac gacagtttat tatatctcac ttgaccagga tcaatgagct ctgacattga tccctttaat ttcgtttctt taatgctagc cttcaaccgc cat cgttgga cgcgtaccca ggacacatcc taccatcatt tat ccagaat gttcgtgccg tggattgaca gatgcagcgg gccagctgga caaaqagaat tat tgagcag ggcaatgaga atgatccaat caaacaattg tattatcacc ttcaaactct ccctcaatcc taaatatcca caacccttat gggattctcc ggacttctgg tggcgagagc tgatgatgag gccaqttttg tgacttccag gacaccttca gacgatgccc tgcaacatct taccatatcc cttggtccga acggactatt cctccaagct gcgcacggcc atgacctgga tatggtggat ttttcgacag gttgctaaca gtttttgctg gaagaaaaga gtgcagataa tttggggaag caacactgca act agatatg cccatacgtt gaaaccgcgc ctgctccatc gcctgqaaca cttggcccgt aggcqgttca tatgcgggcc tatttccggg caagatggta tqcctgcagt tgagtcaaat ttacctttcc gggatatcat ccgacgcctg ccaactactt tcgtctgcaa ccctgggacc tgatggattt atgggaagca catcgggagg tatttagttc ggaatagaaa gggagggttg aaaaaaaaaa cagagcagaa ctagctctga tact accttg aactcttgat catgatcggc tgggtccacc tactttcctc acctcacaaa ctacggtggt tqaaaacatt agtacatccc ttgccggcat tgcctctgac tgcgaccgtc caccaagctt accccgttct aaacaacgct ccccaccccc caaccgcagt ggatggaatc gctgccqcgc cgagctgctg ggggttcgag aggcgtgctg aggacatggt tcccggaata cgaatctgtc aaaaaaacaa tggttgagct gattggtcct atcccctcgc tataaaccaa aqcctaatcc ccgcatcttc cctctcatac tatggtqtac ctcagaattt cgatctgcag atacatcgcg ccagatcaat acaggttatt aatcagcacc tccgacgatt caattcccat tctctagctc tggaacccag gacgtccaga ttcccgacgq qtcatcgaac gcgcagggaa cgggagccgg ggaacggcac aggtccatat tgcaccgggg qgtgggttga tatgaataat gtcagatcqq ccgccaaagc tgtagacccg tcaagacccc gaggtcggat acagtaaaaa cacttttgct 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2660 46/I282 <211> <212> <213> 1540 DNA Aspergillus niger <400> 28 taaacagaac aggaattaac gctcctgttt tgcatgaaqg gatgccaata caccaatacc aaccccacaa ccatatccac caccacccca ccaccgccta atatctcctt acgcgggctc cgacactgat tgttgtttag cgttggagat aggagggatg tggtgggatg taaagtgagt taaagttaat cgttgagata gtgcacagat gagttagcgg ctgcagccga tactcttact tgtaggcact t t tttt t ccg taagcaaaag tattagcctq tacattcccc gtgcagaaac tttccaccag ccttacatcc ctccacccca aacacccccc gctctccctc cttctacaaa ctcacttgtc attccagatg gtttgagatq acagccggtg gccggtttgg gacggggggt gctggtacta tgtctgaggc tacatatgca tat agt tata tatctttgat ctgcacatta ttacatctgc tgcttaatac ggcaatcata gtagtttaat tccagatctt caactgtctg gagacatgct acgaacagtq ctga act aca caactcagca tcatgtccaa acaccatccc tccaccatag tatcccgccc tacccctccc ttcaatatcg tataatagct acggaggagt tttqagttgg tat ataggta tgttgttcgg agtagtggat aatgtgcaat ctggaaatgt actgtctatg ctatgaggac ctttccatct accaactttc gtaactatat cattccaatc gtgtcccctt caccatcatg catctagttg gcgtggtaqc atctccgcgt act acagcaa actctccgct tcaaatctaa ccaccactct tcttcgtcta tgggtaactg atgctgcgta ccggctcgga gtactgttgc ggtgtatgta gcttggtggg tqtggqqatt gacttctgct cataqactga tattcatcaa ggctgtacga ctgtgaattc attttctgga atatatct a C ttcqtttcat aaagaattgt cgactaccaa caacccctct caagccatct acacactctc cagaattaat tacttacacc gctatctcca caacaataac gctcctcctt caaagacacc caacggcgga tacctgtaat ttgtggagat qgatgtggag attgattcqt taagcactat cttgagggtg tctgtgatgc taggtggaaa ggctgaatac gcgtctctga gacaccaaaa qtcaagcaqg ccagaattac tttatttgtt tcggaacaat cgttgtgatt ctaacccacc tgcagt act C atataaccat tatcctccac aggtacttcc aataacctct acccccccaa aactgcaccg tactacqact ggcagtgact gagagtgatt agtccggggc tqagtcggta tggggaattg ggttagagac tggtatgtqa cttgtctact aagtgtaacc ctcctacaat ataaccagcc tat tccaaca tcaatcgtga tgtacaattt 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1540 <210> 29 <211> 2800 47 /282 <212> DNA <213> Aspergillus niger '<400> 29 acactttctt gaatcagcta gttcagcaga agacaatcca ccactcccaa tct ctctcac ccatttcctg ctactcttca qcttctgatc acaaccaccc atggatccgc tcgtcgattc gcgctacggt attgqcccag agatatccga ttqactgatg accaaattcc tacgacctat gagtcgacct cattatcccc cgttggagta caccgcggcg atggattggc atccaaggcc tcccgacggc gaccagccta cggcggtcgg gggaatggaa cgatgctatg tacacggttc gtcttggttc ggagcagcag tacttaccaa ttctgctctc ccaaactttt atcccggcgt gcatcggccg gtcgagcccq ctccgtgact ccactcaacg agtgacgtcg gctgcagaca ctggccgagg cctgatccac ctccagaccg ccatctaaaa gcgccaaagt tggatgcggc tcttacgagg tcaggccct c acctcaaccg gttacccgcc tatgtttata cgcttctgtc acccgcgcta gcacaacaat tcccagccat ataaggttca attctccgac tcaagtgaca actgcttctt cagagcttga ccatcatttg gtcacccacc gtgcaccact gtctgtcatt actcaacatc ccctggtctc ttcaccttct ggatcatcga attccccgcg tact tcgttt ttctattcct aagtcgtaag tgtgaccctc cat atactcc agccgatagg tcggtgacct tgctggcttc gtcgcgaaat gtaaaacaat tgaaccatgt ttctacagqa cctgggagac ccggaatcqa :agcacagtg atatagtaca atactcggta gtgcctgagg attcctt ccc tttcttccca ttaggttttt cataatgcgt cgccgtcccc ctcttcccag gtccatatgg caatcgctct cagcctgcgc ggacgtatgg tggttcatcc gcaacagatt cctaatagac acttgaagga ttttttccac catgtttcca tcccgccctc catcgttacg aatgtacacg cttcgactgg ggaccgacta :cttgaccgc igaaaactat ~gcgctcaac tgaggattca gcattccagg cacacagcac tctttcggcc ctcacgccat tgaaggagat cacctcttat gccggctcca ccctctgatc ggcatcgaaa cctccct ccc aatcacgatg gcgtctactc ttccgtccat ccct cat tat aacctggcag caatctggat gagtatcagc tcccatgtgc cgactgagcg ggtgqtagcc ctcattacca atcatgatcc tggcgcaaga gcctggggct 3ctggagacq jagacacaaa a: ataaagccaa gattgtgggg tgcctcgtct tttctctttc ccttctccat gactcggtqa cactgctggt ttatcactcc cccgaaggcc aacccgcatc qgattctggc aqgccgaggc caqcattcgt atctgcccgg tgggcttgct agagaatcta ttgcgtcctc ctttgtccgt gcatgattag caggcagctc atgcccgcga agtatggcaa ccacgatcaa atcgacagcg tcgaatggga 3qcccttcga acaacaatgc 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 48/282 cgacatcgtg ctactcctgc agcttccttg tcctcgatcc agccaaggcc attcggtacg cat cgt cacc. ctccggtggc gatcaagctt caccggcaac ctcatttgac ggatagccgc CCCcctgccc ctacacagac a ga ta catat aaactaatca caataatgac cgattctttt ggggtattct gacccgagta qaaagctaag tca tcgt cat 3 gccagtgcgc agtgcgttgg *cgtgatcgcg I gagatctaca *gtcgattggg tattcaaaat aacattgacg gatgacgacg tgggccaccg accctattta taatgacggg tattatttta ctacataatt actaactggt cctcataagc acattcattc accttcactc ctccaacgct cgactcacga cagataacaa actggtttta gaagctacgg atgttgttct aatcagaact ccaatgaccg aagacqaaga acgatgatga aacacacata tatqacaccc .ttgcgggag gatactgttc ttactctcaa cqagagcctg aatctacgat CCccgggcgg ccaccaagtg gttcctcctt gaaattggga cttcgatctg ctccccggcg taaggaatgg tgatgatgaa cgaatttcgg tcgcccatat tqattgacgt Zcttcaggtg acaattctct gaagagctag gtcacttctg ttcttcccca cacgcgactt ccgtctgaac tccttcctca tcaaaggacg tatctacaca gtaatggtqg gaagaggaag cgacgacgct actctccttc gtttatcatq cctatagcct aatcgtccta t :acttaatct g :caggtgcag t accccttctc gccttggcct cctgcgaagg ttggtggcaa attcatacca acat cat ccc tcggaggcga aatccgatct acgccaacgg aggaagaaqa aqgaagagqa gatgatggac tgatgacgat .tctqcttct 3tagagctta caaataatg Itaaggaatt qtatcatqa 17.40 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2800 aaatacagag taattcaatg qtttcattcc tacttcaccc qttaggtatc ttccgtactg cactctttac tttccgatgc <210> <211> 2380 <212> DNA <213> Aspergillus niger <400> cccgcctgta caaggctcat tgagcgacct agccgctgtt tagaactcgg aaataggcgt tctatttact ctaacgccta gcaagcaatc ccaagctgcq ccagaaacqa aatgagtccg ctgtgcatgc atgatgcttt Cctcatgggg accatctgac tgagttttaa atatactgtc tggcaatcaa caaaaggtga atgtgactqa tttgttgtga gactataaaa ggatctaact ttatttctat gcatagtatg agtgcccaga taataccatc cat tacccag caagtgcctt aaggcgcggt attgcactac gaaggcttct gacccaatca ggaagctaac cctgcatgct tagtccgaag ctgacccggt ccagacaaca tgaaatcaag tgcagtgtag acagagttaa ggatggctgq tatctgtatt acgcaatgtg ccccgcttga ggacttagac tatt ct agt c 120 180 240 300 360 420 480 49/282 taccattgac atttctcccc tttcggtggc tactcgctca acatggcttt CCtcaaacgc attctcccgc tgctggCCct catcttac catccgacca tccagaccat cccgggga ct gcagttttca gtgccacaga acaggtccct aatgcgaac ggccgcagt aattttgct gaccatgtt gcttatgtg ccttgggga gacagcgct, aatgagtttc gatqttggat aaaaacgct( attctggatc qcggcgataz gtgatgcagq agggtgtgct ccattgagct tctgcacccg tcaaactacg accggctcga acaggtttga accqagctca Cttctqgcct gactaggtgc gtttatatgc tcacttttgc tcccgagact gctgccgttt [a ttgaqtctc a caaccgaa( g gqtacgcgc t gtgtccacc g aacaagatc c tggqgagca g gqagggta 3 gtggtcgtq atggtacac acctactgt j cttcaatt, i atatgagtci tggaggctac ctcttgtgtt aaatttagac acgccattac qCtctgtggt actcggccac tcctctattt agaggttggc acaatggaaa gtaacatgag gaaataaagt cgacaccgca gaaactcaca acctcccgac tgccgcat( 3a tgaccttcc it atcctagac a qgtctggta t ttctcaccg atacgctta tagcctggc a tgtagcaqgg cgtgaagqt, 9 ggccgccaal tggtatgtqc tcctatgcgt gccgctggaE taatgttttc tqttgccgct tgacattttt caacacqatc gatgggcttg tacgcqgaat cagcggcgtg tgaatatggc gtgtatcagc aatatgctgt catccattgg ag tacattqt, 39 gtaacggac -C gccgggat( it gagaaaact :c gtatggttt t ctcgatacg t ggtgggtct t gtagtggac a tataatgct g accatcggg 9 tttgtaggt, gatattgtgi qccctctctc ttaacaatgc iatgagaatgt fcagagagatc atcaacagaa gCcccgggag tccggcacqt cgggaccttg gctgtcacca tcaaaagggg ttagaataqt accctggcct gcttgaggct atgtataaag .a ctttcaagt fc tccacaggc :g aaagaacgt a tcgaggaga c gactaattq c tagttaccg a gcaccgact, 3 Ccggcatctl 3 cagggggtg 3 qcaaaacatE Iaatccagctc gcaaqaaccq gggatctaat agttgagaat aagctctgct cagcacggac gcaatqcccg agcaagtact CCatggctac ctaccccagc atgtggcggg .c cgqcattgac :g cagcttaqaa a cagaattgcc t CCgcaaacat C tgtacaggta a aaqqcgagct El catctatqat :ggctacgcat igcacgttgat Icgqqtttcq gacatcggtc i gaccagtaag cccgctaacc gcttttgacg gaactgtcca tagcccggct tgcgtcattc ttctgcatgg accccatgtg ggctgcaacg tagccccaat 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 gtagcgatga tggagatgag ggggatcgga gttcatgtaa gtt gcct ccc ttctgcacat gagtagacta gtcggcattt cagccagcct gcgaaatgcc gtggtaccgg accgaaggca gacacagatc atggaccgct ataccgcaca qacaacttgt gctccttact gaaagtacca ttccacagqt cattgcagca 2280 50/282 tgatgagtga tgatgtactt ctccccatca agaaccactg gcggtggttg gaatgaatct agatcaaaqa gatcaaccgc ttccccgqac agatcaggcc 2340 2380 <210> <211> <212> <213> 31 2441 DNA Aspergillus niger <400> 31 aaacgacgtt cgcgctcgga atctactgag ggagaatttc gctccgtgtt ttcaccaact gcaaagctga cctataaccc atgccgctac gcccacactc ctcgttcacc attttgaaag caggagactc ttgggaatgg ttgaccagcc actcacgtga ttcctcacaa agccgccccc gggccggtac tagccccagg tgcaacgttc Cttcaatgaa tgacatatgc cgatagtgtt ttaggtcaat actgaagtcg ggagcagttg aagttacgga attacgttcc aacataattt acgatcggtg aaaacgacca tattccgttt ctctctcttc aattaatgct tacacgatga ctgaaccaac ccctccggtg accctgctca atgatcaccc gcagaccgtg ttagggccag accggcattt tcaattcgca ccaattcact ggttggctcg ccagaatgac cccttccatg gagtatgatt ggacttttcq aacagatcac aacccctggg agtcgatgtc gggttttcct agccgcggtg gacatgcatc acagttcctt cccgttcacc agaaaaagct tgctcagtgt attccttatc tggcgaccca ataccgctga aatcgtgctt gggtattgqg aaacactgtg actaggtgcg atattatggc attcaacact cagaccccgc gtaggqtagt atgataacga ttgaaaacgc gttcgggtca cat cagqaag agcagcatca tctctatcta tagctgcatc ct gt tgc ta c ttttqtcggc agggggctga tccaggagca acattggccc atcccctaac aagaagttgg cctgqaccaa atatcgatga qgttcttgcg tttccggtga tctaacaatt aatcttggaa ggtgggtaac tactactaac ggcgaatatg gatatgt cat ggccggcgct ttgattcttc cgtgacctcg aatgcaaagg catttgaatg ttgcttctct cattgaatca tgccagtttg cctgttcagc tccctttacg gaatgactcg gaagcatctt gctatggatg cccttgccgg gaatt cat ca gggctatgag attattcata atcttacgca accttgtgat caaaatgaac ggattcatgt tcaggagtcc ccgcactgta gcggcccagt gatggccgta gctatctagg actactagta ccccagagaa aaactacatt ttggctagac aactgacccc aattcaatat agcgtagtat gtgtttcgca atctgtgatg ttcttttggt actgggggcc at ta atgag t Cttctttttg ctgcctcatg tccgagattt gtaagataga acactgtgta tgtataaaga cacccaagga catctcctat tggatctata ccgtctgtta acagatttga 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 51 /282 tagtgagttg ttatcatcaq aggctcatc ctgcaccttq tgagatcgac gaaatgtgc tgaattcgcc atctgtttgg gaggccctg tcgtcgctac ttctgttatt gatgcattt cgaagcagat cgctttctta ctcgcaaat ttgatctcgc ctgtaatacg gctggcaacq gccagacaga atttaccgca aagcccttac aggaacctgt ggggagtgcg'aaggaaattc cgtcacgctt tgcctttgtg actgtggaca ttaggagaqa ggggtttaat gatccagttg tgccccaaga tcggccggat gtagcgcttg cctttgttta acaaggaaca qttgcoqgac cttttatgaa atgggcccgc tqcctaggtc ttttggacta aggggtccgtc tgctttcatc tccctqctgc ctcqqtccat cacacgcccg tttcgttcta ttatgcttga gtgcccgatc cgcagtttgg gtttttgtcc gaggaagaca 1g ccaaattat 't atatcgaag rt cgccaccgc g Ctcaatcag a atgttgact c tacgttggg( ttCcgtqgggt aggtttcgjgt acqctggaca gCtaacgagt acatqatgat tcaaagattt aaacaagggt agcccttcgt ctccccccat ttccctgcat atcatccatg :t gctaaggat rc ggctctaat a acaggttac c gqacggcat t cttagcgta gaactcgctl Ctcgatcaac cggtgaaggg cctggtaagt agtgttggta tcgctggatt caaactgacc gctcgggcaa agcttggact ttcctttcct gctatgccta .g acgacagtca t gagagatatt c gaatacaaat g gtgtcgagct t caaggcaacc -tcttqgaaag -tctgggagcc acggacgaaa ca aa gta aa a ctatggtagt actgqgcat tactccttac aCaataccag tttgtccatg tCCCttctct tttcaqtgta 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2441 <210> 32 <211> 3500 <212> DNA <213> Aspergillus niger <400> 32 gtttgttgtg gttgttgttt gggqtcccat cctcccaagt CCCtcgttat cttccgcctt ccatcatctt ccagtgcctc aatccaaatc ttccgtacgt gtatttgttt actttcggga cqcccgtccg ccaaggcggc tgcgcctcca tggaaagaat ccctttcact cccccgtcga ttgcgcgcgc tctctctttc ctctccacac gagactgcga cgatccggag aagaataaaa tccgtcatac atgaccggct cccgagccaa aactcaatcg tttgcacttt tcgtcgctgc *ttgcaatccc ttccaccccc actgtcgttg gggagattct gccaagccaa gtgagtctgt ctccagtata ccctccagtgc gatctcgact g ctgatgctgt q tgaaccggac tccacacttt aatatagatt Cgccgttcat a acct cct tg CtcactgCtC CttCCtctgc :agcttaatc ggtccatcc E gaccgaagg 9 cctgtcaatc atttttccat cgcatctgtt tccaqatttc gatcgccagg CCtCCggtcg gggtgtgtga tccggaqtga igtgaaaggg ~ctctgttga 120 180 240 300 360 420 480 540 600 52/282 accctgactc cctttaacct tccctgccct ggcgacatcc caagtgccat qggtcgatca taaagctgga tcgacqcgqa tcaaggggag tccggatctc ctcccatcgg tcattgcaag ggcgcataga ccgt cat qtg ccttgaccac gctggagccc cgggaacgtq gagtctactc ggatctactt gaagcaqgat gcgacaacca tcgaccttcc gtctacatac tcggcttcaa atacgtggqg tcqgaaqtqt cgggctgtcc ccggctcatt cgtccaatgt ccgacagctc gcggcaatct acaatgctta ggcttqgcca ctaacgtcgt acacctttgg cgtcccagtg atcctacaac cagccctggg cctacactgg tcacgttcag cgactcagcg ggaactcaag cactaacccc agcaatttca gtctggcaat gagtacgaag caacaacgag ctacgaaaag atgccccgac cacctcccga ttggaccctq act ctgcaat cgttcggtct cgctgtccac ctgtccgttg tggaacagac ccgcaacagc cagccagtgc tcggtgttgt ctgtcttcac tgctatctcg tttgttctaa tcgacqcttg tttgacatca aaccatgaca cgacggcacg gggcgaggaa ggctcagagc ctgaaatcgg actgactata cggtcgtcgc aaccaccctg ttgaactcct gcgggcggag caagtagctt actgccgcca tccttcaaca aacccgcccg ctggatctgt atgagcgatt agcgatgctt :ccggctcgq 3actgtgact acctcgagca itcactgcgt t Ittaagtcca g jgcaacggaa t tttgatgcca tcgctgacag ctctttgggg ctggatcaaa accagcccac ccttcaatat tcctggcgga aqcccattgc aaggcatgtg cactatttga catacatgga tgatcttcta tcggatcgac tgctacaacc tgtttggact tcaatctggc tgattggtgt aggaatgggt ttacgattgg cqqccacqgc tttccaagtg gcgcgacggg cttcggatgq c attggcagat c :ccagacctg c :ctgcaacqc c :ctcgcaatg c ittqtctctc c tgtcgagtc c gcacqctcgt caatgcggtt tcaatgtaca tacagctcga catcaagaca tcatgacaag agacgcatcc tccacatgag ggatccggtc gggagtcttc gaagaaacgc ccgggattcg ctcqtgtcaa gtatggccag caacaagcgc gtcgaccatt tgcaacggac catcagtact gctgcggaat atggaacatg jcgcggtgag :aacgaggtc ~tcgagcacg g :gcggaqgat c :aacgggaaa t :actatcgga a gccaaccgc g qgcgaagac t aagacatgc a tccacactca tctcacttat aggttagctc tcacaagctc ccctcacagc caccagcgga gtacagtatc cataaggtct ggatggqcgc agtatcgacg cccgtggatq gatatggtgc gccgatcagc gcagagaccg caatccgata ggtgatactt tgcgccttta gtcaacagcg ctgactatca :Cctgctcca aatcggatg ~gactgtcat ;tcagtggaa raatctggcc ;tcgaagcct a ca tcat ga atatatgcg acgtcacca gcgattgtg agttcaagt 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 gcgqqgaaqa tqgttgcggc gacaacaact gctgcgacgc 53/I282 cgggagctgt gtgtgatgac tccaacgaca gctgctgttc aagctgccaa ttctcctcag ctgqgacggt actccagtac gctcgggact tgatgggcag gcgaactggt tcgacggcac acgtcgaatc gcgccctgat cgccaaaacc cgccgccgcc cgcccccgta ggtacgcttg cqattcttgc ttacattctt cttttctata atccccaggg tgggatgtat ca taat atat atgtcgtgcc ttgtcctacc tgcctgcgct tctcctccac ctgcacctcc tccctgcggt ctggatcaag ccttttggcc cgtcccgcgt cat gaaccag tccaggtgta attgacgaga agcactagca gtcttggagt cggggtctg ggttggttcg ggtcqgggtc tgcttcttgt agtcgcggcg gactcgttca agtggccaat agcaacgaca ccgaagatcg agtggcggct aaccacaaag ctgatgacct ccagtgcctt tggccggcgc cctggtcagc Cttcttctgt ttacaaatgt ggaggcgtgt ggcgtttcgt cgtcttcttt tgatgtatgt actgcgacgt agaaggacgg gcaccagccg cctacgcctg gcacgtgcta actgcagcaa gtatcgtcat gcatcgtaaa acgqgccgtg gaggctatca cagtaccgca gcttctttcc gacgatt act tctagagttt gaattgcagt ccctttcttt attcctgccg ggcaqagacc cacgagctgc cgactaccag ttcctccttc cagcgtcaac cggcgactgc tggtgtcgcc ccgctgtcgc gcccggcgct aggcttaqggg acatatgcct atgcgatata tcattgatcc tggtttgatg acttacaatc gcccatatta tgtataatga tgcagcggca ggcagcagtg tgccgcagtg agttcctcct caaaacttcc aagggccaaa tgcgccgtag cgggct cgcg aggcctcccc aatgagccgc ccccaggggc gtatgcatta tttattgacc ctgaattgtt caggggtgca gacggggccg acttttccgt 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3500 <210> 33 <211> 2520 <212> DNA <213> Aspergillus niger <400> 33 ttgatgcata atgctttcct tcagaggtaa acatacqatt ggtatttgac gatatttgtc tagtgtcatg ggtttgaata aagacatatc cgctcttgtt gctccgacga aaagcgactg ttatcaacgc cccgtcagca ctaacagttg ttttcgcgaq aaacgcgtgc tatcgcgagt agcctgagtt ccgtgatctt cacttctact tacttcgagg atgctataca gatgtatctt cat cgggccg acatgtttct gcagggcaat tcttcttctt acggctatga tgaaatttac aatagcaggt atgcgggtcc ccaggtcggc tgttgcctag ccctgct ccc agcgtatgcc atattgtata caattgatga agggtcgtcc tagaaccgcc cagtagctaa aacccattac 120 180 240 300 360 420 54 /282 tctgcacccc gcct cca ccc ccatatt ccc cattccgccc tttgagagcc ggggggtcca ggcaatggca gatcagccag tcgcatcaag ccgcaattgc tctaggtcac tcagatcgtc tctcgtaggc ctgcaccact ggcggccaat agctatctgc cgagtctggt ccctgtcagc gacggcatat tgggctgctc tcgcgcgcat ctgcttgcga acgqcgggta tcgaaggcgc ggaacgacga gcgctagtta ccaagtatgc gatatcgcgt atgaatgtcq acgcccaaat aggcggtcct cgcaccact c aatacaccgg agaatgaccc gcatgatcgg ctt act acaa tcgatgtggg ctgcaattga agactcttcc ctgagctaag caacagaaca aacggctact aaccctggag atgccqcgat catgctgcgt gaaggtggtc aaatctctgc gctacatcga tatcaccacc t cgatctcac atcaqgtaca atctgcgctg t gcggccatg aggaggtgag cggttgatgg ggattactaa tggatatgat cagacqatgg gcqtttccta ccagccagag gatccgcatc ctggctcgac tqccaatgat tctgtttgaa tccgtggggc attttcgtac cat gcat cgg cgttcatctt act aacttcc agctctatcc attctcctcg tccccgagcc gcatggaagt cggaggtatg ggaatagqtt aatttactga ggccgctcgc caaagaaatc ttcagacacq tttcctggcg ggcgcattct gagttgggta agtgaaggtt ggcgqgacat tggtctatta ggtgcgctgg gataccgqca ,agcagtgcag igaaccatccg cgccagcaga atcggccgta cccctcactc gaagtcggqc tggtcccgga gtcgatgaag ttcttgcagt tctqqtqaat acagggtcac cactgagccc cgacactacc cgtcttcaac atccgacgta ctacgagggc tgatagtqag tatgaaacag atcqagcagt aaagaataca atgacgccag tatcaggca ctgccatgga gatgtggtat agtgagagta tttgtgagta caacttttac atatccgggg tatttcacag ccctattcgg acttccgtac atgaatcaat aacatctctt tctggatgac catqtctgat act cct ccct gagaggacct tgtttgtctc cgtatgctgt tatgtccctt cagcjtccttc tacggctact cgaaccagat tgtgttcgga gtgatcgqat ctttgcccca taaccgctcc acctgaacac aggttacttc cgtctgagca atctcgatct gaggtcaqgt ctggaaaagg cggataagga tccctttcgc agcttcctcaz cctqgcgtat attccacagc ctgcgctgcc cttctggtac aggagggcca caatgagtac actatttgtc gccqggcgat ggaggttttc atgtatcttc acctcggcag tgcactcatg gggaaaccct gcgacat cat accccgatcc qgtatgatga tccagttgtc ctgcgccctt acccgcaqtt cgacaatgtg agtcgcgttc ggcgtgtaat cgagttcgcg tggagtggct gtcgaggttt ttgtgggat ~gatagacct gagtgaagc ~tatatgtct 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 tgtagctgtc ttcagcagta tttacaatat gctgctgcct tctctgattt gggtataatt 2220 /282 atagtttaac cagcgatgaa acaaccctgt tacatttgtc gccccagtta acaatcaact tttccgtcta ttctttcctc atot acttct gttagttagt gcatcggcag agatggatgg gcttgatttc gcacccgcag aocgagogaa cggtagcgga cactaacact gattgtattt ttgatttgag aoagaagtat gtaagotagg cgtagtagaa aotgagttgc ataaogtaag cgactattgg ocgctacctt agtagtgggt gocgaagtca goaoacattt ttcagccctc 2280 2340 2400 2460 2520 <210> 34 <211> 1721 <212> DNA <213> Aspergillus niger (400> 34 attgatacga ccagtgggcc tggcacctgc ggcgaaacgc agggattgtt ataattctca atatgacatt caaccagatg agtcactccg ccgaggagag gcagcaatga attcaacttt Oct atcttca gtcacataaa gaaggggoaa acgagaattc cat catcaac ctcgttccag gtttagcgca tgctgcatac acacccogga atcttcctgg ggcgtttgta tatgttt tog tagtcgatgt gtctacccct tgggattoc tottgtcctt gttactcaac cagcgcactg agcggagoat ccgggaggtg agcagcaaac tgacccatgc gaaggcatat tgactcgtgg ttatggcaca tcgggactat tgtcctaggc ota oat oaag gtacaacaaa gttcgaaggt gcaatct gag oct tgat got ggtggcgttc tgatagtttc gcccttcctg tctttgggat cagattccac tgtcctcggt ttccacgcgc ct ctctggac aggaqqctgt gtgccttgga acagtatcag ctgcgcaatg gaaagtgoga gcgcgaaatg ttaaatgtct ccaaatgacg ttctgtacgt gatggttgta ggcggcacag gaatcgtgct cot aogagog attcataatt ctgaagagga gga t ttot a atggagcgat aattooctgg gtagoggttg goagtagaga totttaoagt gtgaottttg atgatqtaoa ttgaaatoga aoqaoatgat t cgt gt ttt g otatoaoota atgatgaaot atttooaaao gtaacogaog tgootgaooo aogtgtt ago oggttoatga ooootgataa gatgtooogo ttatggacta totgataooo tooatotagg otoaaagtgt tatgoagcat goaatgatgc atottoaotg oattcttgtt ot ooaogcoa ggoocaacgt gaoatggttt cacoagocag gaotaaoaag toggttggag ggggatgaag agatctocag aaoagatgtg gagtgtgaat ggatatoatg ggttggcoat tgaaggagat cgagaaagat ttoatotgat aotggttttc aaaattttga oaaatttotc tcotgaoaog ttatgatttt ooogataooa gooaatcttt gogocoggtg gacagcacog oat att gtaa gtoogtoaoo tootagcttt ggoataactc aatgoootao gogtcatcog toagatcaat tccagoagoc ccggqt ggt a tggaatgggc taoattgatg toatgoooog gactgttatg 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 56 /282 agagttttac ggaagtgacg aact at ggt a ctatcacaat agacactcgt tgcgcttttt ttgattcgag tccagatcaa gacggactcc gcacgaatat tcatgaacct tcgaaattca tccacgatct ttcgtcccag gcggagagaa aagggt at at tgatgtcaac tttgtagaat cagctagctg tcatcgtcca tcttcaccac tgaggagtat aatttgcaca atcttggtct ttgtgtattg tcatgtqgaa ggccactttc tctcttcgtc gtggtccgct tataccagct ttcaattccg gagagcgatt tgcgaaatca cctgtccttt 9 atgcgggaag atagatagac tgggaattga gatqcaaact gatcatcgct ttctttgcct 1380 1440 1500 1560 1620 1680 1721 <210> (211> 212> <213> 3550 DNA Aspergillus niger (400> cctatcctct cgacaagacc cga taaa ccc aatctcatcg caggaaacaa attgtccgac cactagtgga ttcqtqctga tgcagggctg ggggaggggt gttttgtttc ttttgctcgg ctgattggcg aggcaggttc atgctagtca ccgttcctga ctcacttttc tgttcatgag aggtgcccta gct ccgcccg caccagtgga ct cat cacga cacaacgacc attatcactc tccgaagaca ttqaattacc tcaggqggtt qtcataacaa tcaccgttga caggcgccct acgcgggtct atggatgtca ccttccqctg atggqatcag tgatggcttg ctactcagtg cgqcqcqatg ctgcctatgc gtggagagga gataagagga taaaccaagt caaaatccag ctctgggtgc agctttggtg cacacaccca attttcttgc tttggtagtt acaatatgct gqacagcctt tgqtcgggtt cgcctcttat qgtatgqaag cagcgttctt cat gccacgc ttacggcagc cattqcccaq ggatagqqct tctattgacg ccgaaactat tgggct tact caaggcacga tgatgcagac tctggtgctg ctacttatac gctatttggt tgggttggqt tgtcgttagg tggctatcag gacccagtgt cagggtttgg tgcaaacqcc qtcaactagc ttgctctgtc gtttgccagc tqtctgggta tactcagtcc ctatggttct ggcttgttca aacaaggcca tccaacatac caactcagta atcgtccgtc tctttacqct ttcccactat qgcttgttat taggttgaac caatagctca gatctacgct tgat cat att agcqtatgga atatattccg gctgcgatca ccaacacccc gaagaaagcc aacctggatc tgaacaatg aggtctgctt atccttcaac cctgtaatga ttccgcgtgg gtggagccac gtctatcatc gcttctgttt qgtcgatgtc tgatgcttgt atagctggtg agacgctttc tagcctacat gagtgaagtg acgtttccca acatgcatgt ataactatgt ggctggacaa gtggccatga 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 57 /282 tttattgatg ctcatccaca ttgccccgtc ctccaagccg gcgaggttga gttcccatgt gttaggtacc aagatgctgg ggcagtctgc ccgctagcac cccaattcaa gccacaaagg gacctcaacc cacaactaac acggcgccac aaatcgccta actacgaaga gctcctattg gctactcctc acggcagccc tgaaactcgq ccagcacggg catgtcccta aggaccagga cccgaccatc tcacctaccc acaaccgcat acaaccaggg ccatgttgac tgaacccggt gaggtgtatg atcgtctcgc gaatgaggcc catct cgcaa gcagcttctg gacatgccac atgtgcccga aagtgcgcgg ccccaatctt actgcgatct gatttcacgc gcaacgagct ttttcttcgc accaccaagc cgccccaaca cccaat cat c caactacaac caacgaaacc ccccaagcaa cgaagccgac ccttcagggc cacctgcttt tctcaccgca aatagcagtc ctaccagaac ttactactcc cggacgagga cgaagcgaca gcgcattaac gctgtatgaa tgttccgact tacggaaagc gtcgagaccg tcatacaaca cagacggaat gagtgagtcc aaccatccaa ca cgccct cc agcaccacta ggcqgtaacc taaccgtcta cggcatcttc caacttItgcc gacatcccac gacgtcacca tggccccaga ttcaaaggac tcctctctag tgcggcgtct ctccccatcg atcagcgtgg ggcgatgcag gtaggaggca acccgcttcc cactccgtgg ggagtaaact taccccgatg ctggtgggtg gaggagaggcI catcctgagg cctcaccaga atctctccag tccgaacctg agcagtggct actacatcta attttctaca tcgcacatcg aaaaagagag ccaatcaata ccagactgca gccatgtaca gagqacctag aggttcgatt agggaaccca acgccggccc acaccatcct tcctcaacaa accctcaata acacccccac cctaccaacg tcgtcgcatc acaacgtctt catacctccc cct ccgqcgg agacctattt acacagactt tttcagctat gtacgtctgc :ggcgaaggg cgtttaggga1 accaagctga cgaqgaggtg gattgaatcc acagttcqat cacccatgcc tgccatgaca actacataac atgcagagaa tcacgaagat ttcgaggtac acatcaccaa gagacatcta actctccacc tccaaccctc cgaatccgac ctaccaaacc ct tcctct a c cccagat ccc aaacgtaatc CCgccaatgc ggqcgactcc Cgtcccagat cctaggcgca cqgcttcagc ctccactacc ctccaacaca cgcaqacaat :qcggcgccg gaagtccacg tgtgactqtt ttgtccaggt cacqacctat gccggaattg gcccatgcaa gacacgggaa ccgctaacca accaggagta gcgctctctt tttcgacgac gttcatccat aggaacaaca cagccaagat ctcccttaga gactccatcg ctggacttcc gacgacccca gccatcgacg tccccaqgcg tccatctcct cacgagttca ggcgtcgcct ttcccagcca gacgcagcca aatatctacg agcgacgacc gatggggtat atcatcatct gcgttcgcgg gtggggtttg gggtcgaatc 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 58/I282 ccgggtgtgg ggacgccgcg aagatgtggg at attact ag tgatgcaaat cagttcatag actacatatt aatgcccaaa aaaagtcatc gcgggtggat agaaactgag gactgatggg gtttgaggat aaggtgtaat tttatagcct gctaaaatat tacagaaagg aaacaccaca tgctctgttc tagcgctttt gattaatttt ttcccggttg ttgatggata gaagatgatc agtcaga tat tgat at act a ctttgatcag act cgggatg gatcatatct ctgaaagttc gtatgagtga ctggggggtg tat ttgtggg ctatttaatc ataacattgt ttaagcaact tcctagttca cttggggtat tggttgatgt tattatgaga ttctatagac ggatccggtg tgatgattga cggtaatcta act act acta acattatgat ataaaaggta agtgatctga catgttggac attttgcttg gttgatcatt acggggttgg tqgctgagac ccacacattc tagaggcgtg ctaaacttta tagactactc gagtcgcggg gcattatatc tttatagcta tccatgattt 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3550 <210> <211> <212> <213> 36 2280 DNA Aspergillus niger <400> 36 ctgcctctca tgagttccct tgacttggtc gggataggat t ccqgcccqc ttcaatgttc tcgttctacg ctggccacag gtatgtcaat tcgaggtaga caacactctg ttgattcatc cggctacaac cggaggcact ctcatatcgc tgggttcatc gcgaaaaccc gaatggtgga ggcgtccgta gaaactggat tagttccacc cacctggtcg tcqtttattt ccgctctggg gagaagctca ccttggaacc ggtgcttgat ccaccattcc ctcacctcta gtcagcggct cagagctttg ggcctggcat caaaaccaaa catttctaga tcagacaatc aattgcggac agatgccata cat agaaggt gtctcactgg acatgtcact ctctacataa atccaaaatg aagtgtattg gctccctgag ccaggtggcc agcaattgta ttaagcctac ctggtgtcaa tcactgccac ccgt cat tac cgtctaccat ctgttagcgg tagcggatgt ctatctcatt tgtctcggat atagaccttt gcttccaaqa gacctagata aaatatctac cgtttgattt cagatgattg actaatcacg cttaggtgtc ggatattctc cgacagtacc cgcattcaag ggactatttt cttgatgatc tgcccaacag tattctcgaa acgccgtttt ccctcctact tcaaggttca taactcggcg gatgtacgac tccaaatgtt agcgccaggt aacgacagca acggttcccg tgggcggcct aatactacga tagcatgtca acacaaaaaa cat cagtcgt ggtctggtat gttttcttct cattccggca aaatggctat aagaggacta accggatcat agcgggt tag actcccgaca ttgcttacag acaccaacgt tagcagccga cagccgtcga 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 59 /282 00 00 acagatgatg ggaatcgacc ccatgaggaa aatatacaaa gtcaagcgac accacactgt ataagcattc gacatctcat tttacaatgg gtgcctggct aacacgatta ttcgacccgg ccgagcgctt ctcggacgtc agttcatcgt caattgtttt agccaggaga gcgggctgtc acaacattat gcccgcaagt gggctatatt cagcattgat caggatggac gtgaccaacc acctatgcgg acaaatctcc gtcctgaact tttctttagc ccaacgacca ctggataccq gcttctatgg atcaggacga ttggtcagca agacatacga gacctaagaa aatgtttaag ttaaataagc atgggtcggt tggaacatga ggtgaccctg ttcttcagct ccgcgtcatc ttcggttcta ctgttataat ttttggatga ctaatccgga acggggaact ttggaattca ggtacggcca ttgctagact gattgaqgcq acctctgtgc cgagggtgtc cgaccactgc ttggttgagc tatacgtgtt cttctattcg catgcgtaaa agcttatctt gcgataaagt aagaatctta tgqgcacat caaccatgaa aacaaatatt tagattgtta cctcatattc acctcgattc gaataatqgc gcaatggatg gggacacaac ggttattttc aatctattca atgtatgccc tccgatttca accttcaatt ttccctccct aatttctatg gggctggctc tgtctttgag act at ctact cattctttac ggccatctaa ctctttgtca ctccggggag aaggttcggq gcgaagaaat gatataatta cgcgagtcac gccatatatg qtgttcacct aagatgctct aactccgatq gataccggta acgtcgcagg taacgccttt atgatacatg tgaccggtga tcaatccatg ctgtattcga ctttgaagaa catttagttc agaagttaat aqccactata aggcaatagc tggcctcatg tggagqccqt gacctgcatg ggtacgcttt ttgcttgtcg ttgattccgt caggttcagg ttggtggcaq ccccctttga gccaggccct ggcattttct tgcttcatcg ctcatacqct gtcgatctct tcagctggcc ggacagctac cttcggatca ggaatacctg aaacctcttg gttcatcgag cgcgacatga aattaaaata caactttggt taagcttcgg catcccccaa agagccatgc aacccagatg gatcaagatt 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 <210> 37 <211> 2287 <212> DNA <213> Aspergillus niger <400> 37 taqttgaagg aggcttttgg ctttcttcct ctttatcttt gatcgcagaa gatgtgcaca agatgaagac cgccccgagt atggaagaga tctgacaacc aaggagtttg tattatccag tccgtctgat agttccacca aagatactgc cattttgtat cttctgttgt cagtgattct catctatgga tactgaagag ttccagtttc atgttttgcc ccgtagttag acggagacaa 120 180 240 /282 attgacaacg tataccttgt acgtggagat tccttagcaa cgccaccgct gct totgact gagcctgccg ctacaacgat gactttgtca caaccacttc cggtcccacc tagcgcattc tgagttgttt caagcgtcct atct act gcc ctaggcggat acggaggcga ttgaacctca ctggatggaa ccagtgtctg ctttccgatc agtttactgc cccgagaact accctgggag tatgtcatgt tataaggatg ccaagaccgt aagtaataca a gt aat taat gtggatatac acagccttgg tgctacgtga tctgcagcaa tcggctagga agtgctgtac cgcagttctt tatctggttg cccaccgcca tccactttta tactttacgg gcggtgaaca cctttctcqg ccoa ccgt 0 tctaccaagg acgacaatgc a ca aca cct c tcaacacgct cgcgcttct C agcaagccgc tgtacggtta ctccaaataa caccgctgcq atqtqgaggt atggagcgat ttgactttga tgtgtttgaa agatcatgat tgtgataata act gcaaat a gga atat tag gggccaagtt gcgtacgcca acgcaggaaa tgtttccctg ccaccagtct acgggtt tot actggacctg cctacgattg tcaaccaaac agcccgcagc ccaccatoca gaotatataa ataaaactaa atggaggagc caccaaagcg tcacgtccaq qgactttgtc tatcggagac cgttgccgcg ccagcgtcta cggtgagcag gtatgagttt gctggcgaac ggtaatggga gaagttgcag catgtgcatt gctatctgct tot ccaaagt gcgctgttcc aggtcatctt cagacatact gcttatcgac caaggaccag ctctcgtatt ggccaccacg tactgacata gacoggocac tctcaacgtc tgaccagtat agccgatgtg agcagccaat actotoacct ttcatgttaa ggogcctggc gtatgcagtg ggagatatca tat gcgccag gaagagcaag ttcgaccacg gtcgagctgg ggattctatc gccgggtcag ggaaccaata aattttggcg gtggggattg atctcgagtt tgattatttt a gta att aa a acattgagac aataccatac tccagccgca ctattttagg aaattcgtca tggtctctgc cacctgcaat gcccttggaa tatgtggtga gatcaqaaaa ggctatcttt gcgacggaca ttcgtcttca gtttttcagg cacgaatcat act otccaat gttacgacgg cctggtacga ccgtgattaa agctcaacaa cttcgtatgg tcggggcaaa agttcgattg agogggcgt g a gtgoa cot t agacatttgc cagacttcgc tgactgaata caatgtct ct agagaaaact aaccatataa tagtggatao cgcatggatg acctgctccc tcatcgttto tcgttgcagc cggttgactt ct ccgggt ca ccaccttgtg ttttcaaoca aotgggatcc tgctgcgcat acgagactat gtgacaatog aggatccgtg tgtctctttt ccttcagaca catcattgtc t tat t ggg cg gaccactact tcgcggtgcc agccgtcacg ccggaactcg ggagattgtg taatgtacgc cattgataag gtggtaatgg gacggagaat agtatgggga aatcaccact taataagtta aaccatccgt 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 61/282 acatacggaa taggaaggag gagcgagatg gtcatcattt gacactgagc atactgtgtt ggcccagtca aqctqttqta tgggggagct cctaqtgtgc ccaaggctcc aqcatcttca ccttccgcaa cgactttact tagtttacat taggtgagcc tttctgttac atagttqatt gaaaqcctct ccccaattgt cttagcatga tagaggttac tcggagaacg tactaatcag gaggcca 2100 2160 2220 2280 2287 <210> <211> <212> <213> 38 1950 DNA Aspergillus niger <400> 38 gatctttcta ttattctcaa tctggct gag cattgcttgc agcagcgtgt gtcggacgac aagcqatgct cat caaaagg ctcttggtct cgtcaacatt tacctgggtt ttcggacgat tgggtctgtc catgactttc cattctcggt cgttgcagaa cgccaaggat cacctacacc tqttggcggc ttatgctatg atct tcgggg ctctggtgtg gagcattgtc tctgcctaaa ataggagagt acctgttatt ctttgcgcca atctcagccc ctagcagacg attcccgttc aacaccgccg gggtctgatg ttcggttcca tcttcgaccc agcggcttgc ggacttgctt ctcggtcgaa agtaacgttt ggcacggtca gataccgtcg acttcatgcg ctgccttcaa agctaccaca aattacacca ttgattgtgt accaaattct ccggcatct c gattcttcca gtgccacggc gtgattcatt attccacctc gtcgtgacaa ctctcgatca agaaatctat actgcacgtc ttgaaatgac taggaaaaga ccaacgcatc ccaacgatag tcaagtcgaa gctttgqcac gatcggacag atttctccaa gcgactcgaa ttattccgtg tctcgccgaa cattctgtca actctatcac atcgtctgca agttatgcat tttcatccca agctcgtcgt atctgccagc tgatttcaag agatggtagc gtacatgttg cacaccctgc atcggaagag caagctcacg ggataacttc ttcctacgac tatcgttqgc tactgacaag ctattggcgc caaatcagcc gacgctgcac caacacaact ggactacgtg ttgactccgg tacacatttg tcagacaatt ctcccacagc tacaccatca ttcctgccag gatgagtccc attgtggtag gacatttcat ctcgacacag acgatgcaca tggagtgtgg attgcaaatg gagtcgtacc aacccaacat ttcgcccttt gacaagtaca attcccgtgg at cat cgata agtctcattc actaagctac ggagcaactt ct at gaa at a tatcacctga gcgataaatt gtctcgttac aactcgatac taccaaaacc tgtcactgaa cggaaactcc acatctctgt gcqgctctga ataccttcgg gctatggaac tcactgtacg caatggacgg tcatggatgc cacgtagccc ccggcgatat acgatgtcta ccggaacttc ccggcgccaa aagtggcatt cagqttctgg 120 180 240 300 360 420 .480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 62/282 atgcgtttcg ca cgtt tct C agagcgttcc ctcgggatcc ttcatctgat tgctctggcg tgaacctcgg cttcgagcct atcaacattt ttggtataga gtgtatgact aa cat tat ca aaaaatgtqt tcgaacacca actacaacgg gctgaatcag attgcttcct gaaacatatg ggacggcgtg attcttactc acatggcatc tcgqgtacga gctacgactt atgctgtgtt cctctgcgtc gcagctcaac gaagtagcat tcatgctttg cat tatttac cgggtcatat ca ccagtt ct cactacctgg ttctgacatg atttggtgat tgactacgat gaactctacg gactacgacg gaccatt ccc gctctagtta acatgctgct taccttacat ggctcgcaat aacattcaaa gacatctggc gagttacgqg agctctggaa aqctctgcta gctcctcagt accgcatctt gatttgtatt tcgaagtcct taaccctqtc gaaccttgtc tcctgggtga tcggatttgc caagcagcac gctctagtag atttcttctc actcgacgcc tgcatatatt tctctaatca taagaaaaag cgggatcagt 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1950 <210> <211> <212> <213> 39 2660 DNA Aspergillus niger <400> 39 accttctggg gcctgacagt cccagttggg cgcatgattc aacagttata tcatgtaacc tgggattcgc acccgatttc gcacgttatt ggagtgtgcc agagcaagac tgcctgattt tttgtcaact tccttttggc agctcctct a gtggattatc tgatgcctga ctgaattgac atttccaagg cctagctatg tccgtctctg cgggttctcg qcatggcttg cgtctttcag ccgtgqtgcc cctgcgtcga cgctccatca tgcagcagtg a atct tgagg qtgatatatg tgaagagatg gggatgcttg cacatttagt aacccaaqga cagcataaaa gctcaattct gcaaccctaa gacccctgaa ggtCttgggg ctgttttgag tattgacggt aaatgacgtc ccctatcgag at qtccat at tcagtcagct aactgccccg tat caggtga tagtgtcagc aatqgtcaaa qagaaaaaaa ccatccaatc cctctaccag at atagtt cc ccttggcctt cttggatgcg caatacactg ttctaccttg ccagcgagat tgccaagcgg ctcccactct cccaagtgca tcccggctat cttaaacaga cagcaaagga acttgaactg acaattcttc taaagqttga tctacgtgcc ggggctgcca attactatca acctcagaga cgccttgccg gattcacttg gatagctcca ccatctatgt agaagatgat ggtqgtctaa tgaggctttt ata atga ccc atacgaqcca caagcaaact tccttccccc tgaatatgga agcgggcggc tcacttaata accgtcgatg tcgcgttggc tggttccatt agacagtaga cat caactcg 120 180 240 300 360 420 480 540 600 660 720 780 840 900 63/282 acaaccctaa caatcaacag ggcgacagct actggatgaa cgcctcaatt ggaacccctg cgcagtcact tcgatgagaa ccaccgattc act act ccta acatgtatct tatccatcat tcaacaccag gcctaatcgq cctccaaatt atccattcgt ccacctaccc acctccccaa tgatctccac acacaatctc tcccgtggac aaactcgtgc ataatcagtt atgagattgt ctagtgttac tcacgacggc gggcgttttt at tgtggta c cttgatatgt ctggaccgtt gtaggaccct gacatgtacc ctaaactct a cttctaacaa gacaaagcgg aagtttccta ttacgaatgt atccacttat ccttgatacc tttgtcctac ctgaccattg cttcccctac cgacaacgga caacgggccc caccgtcgaa tat tccctcc ctcgaccgtc ttcaagattc tctagccatc gcgtgacgga ggaqctgggt tgtgggcgtt ggaattggc qgcgtatacg qacgtctagc ggtgccgggg gattattctg ataatgaaag gtctactgct accttgatac ttttgtccta gtactatcac tacccagatt acaacaatgc ctagatctta tctgacgatg cagcatctca ataactcttg atttcctgtc tctaaccacc atcctgqtcg aacaccacca ctgcaagcct gct gact ccc tccaccccca caatccctct tacggggtcc ggcaacatga ct at gcaagt gttccctttc gcgacgctga act gggacqg cctgctgctt gggggaggtg gtgctgggga taggttaaag tagtatagtt cgcagtgagt cataacactc catttcctgt gaacagcaaa cgcgctcaag aactctgctc cctacacaca gagatcacgc agttccccct acatagacag atcggcct cccccagcat tctccttcgc tccaactaac tgatgctcag acaccgacct ttccctgcgc ccttctctgt tcggcattca tgagacggat aggatgatga cgttgcctag ctacagggac tggtgccgac tggctgtttt atgtatattg tgaatttttg gatatagtgt ggagaccacg cagccccttt tgacattcaa ggtcgagccc cgaattcggc gagacacgat aaccgacaat ctctccctta ctccctcggt caccacctcc catctttgga agaccacagc caccaacacc aaccgaagaa taacataacc ccgccaggaa qtcctgggat ggcccaggat gtatgtcgct tgatcagaat tgctgtcggg ggcqgctgcg gqqtctatca gcaggctgtt tct gtta tt g ttatacacca agacccgtat caaccgacaa ttgaatgtac tct attct at gcatacaccc ttctacaaac gcaggtgtcg gtcccactgg ccaccctatt ctctcctccg ccatccttca ggcatcaaca atcaccaaca aacgataatt ctaatcacct atggacggcg accqaatctc gagctcttcg tcagattaca gtggat tat a ggaggtgaag gattggccqg acgttgacat gagttgggta taggttagag tacttgatag cgtgaaccca tact agt cat cgtcccactg ctacatccct gcatattacc 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2660 ctatcaaatc acgtgaacat acagccctcc caagtcacct 64 /282 <210> <211> <212> <213> 2501 DNA Aspergillus niger <400> tgattcccaa ~tatgacagaca t ttgaatgcag ~1ccacctgaaa 00 Sccccatcgga C]gtcccaacac ccgccttgca ccagcccata ccccatcgca tctcccccta ctqgtcttcc cagcaaccag gagcactct c gttcaaccaa ctgggccgtc gtttgtcgtc tggcatcgcc taccgtctcc cattccgtcc cctgatcttg agtgtcttcg gggttcctct ggttcaggcc gacatgcgat cttctgggac ctttgtgttc ccagctcaat atcqcaccag gaccctcaaa ttggagaagt tctgacaatc tgaacacgcc ccaaaccaat gcaatgtgct tccttcatct qgctgtttga ctqggggtat caaqcctacg cagacggtcg tgcacgaaca aacacctcca gagggtqgaa cccaatgtga tatcctgtct aattcgacqg tactCgtacg gggggctacg agtggtCttt cccttcagct aagaCCgtcc gccatcacct accacgagcg aacatgaatg cttacgctgc atgaagttga ttgaagcaat caatcccccc agcaatcctt tcatccctca cctttagcgc ccccggtcgc cgcagctttt atgcctgctg ttctgcagac gtccagatgg atctttaccc aaaccctgtc ccactgccta qccaaqagqc gcttcgaagC cggtcggcag tcctgaacat gcatgcatat ataagagccg tggaacttga tcaacaaCga agattgatcc ccaccatgcc atgattatct gggtcaacaa aagaaccqct atcagtggta ggcagataga ttggaaagcc cagctCttct ttaggcatgg gcaccgggcc attcctttcg ccctactcct aagtatccat ctcctcggca cccgtggcag cqgagccaac atccacctgc caccaccgcc tgtgctcggc catctaccag tctggccctg gatcgcagga cgggtCggta agtgatcgga attaaaggat aagtgqcttg aaccaagccc gatctccttc gaatatcacg caagaacatt ggtcgatcaa cagtttagCg tatgqtctcc cccaacgttg cagcgtctct ctgaqctgca tgcgaagcca tttcataatc tcttttcttt ggtatgatgc tccaatccct gccgtatcca tatgctaqca tacgctgccg aqctcgtggg gatgaggtca acctaccaga gggggtccgt tggctttact gaccccaaaa gacgtgagtg at tgggct gy tttctccaaa tacatgtacc aattccagct tcttccgccg accatcaaga ggtggctgtc agtCcaCcga cgctttctga tggggccgat tgtcagcgga tcaccatcgc tcacctccgg tgctttcttc gacCgatact atgtaatgag tcgacgtggg cgatcctgat aagcaggcac aaacaactta ccttagggtc cctatcccaa acttgtcgga cgtccaacga tcccaggctc cgcagggaqt gtgttgcggc gcagtqgttc ttccccaggc tggggctata catacctctc ttcccttttc 120 180 240 300 360 420 480 540 .600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 aacgtcacct acttcccgtg 65/282 00 00 cttcctcact ggtgaactgg gggttacgcc taacggtacc gagcagctcc tgtcggtgga ccgcggggcg ggagctaccg qccgccgcag aattctaaat gcgaatataa acgacttgtc cagcatgacg accctctctc taacacgtgg acctccaccc ttcaacggqa agtgaagaca tgggaagaga aagagtggcc gcagtgttga agtcaagagg ggaggtgctc gaaatgatqg tttaatatgc tagctagttg tccgatacat cat tgctcaa acctctgtac atctagaccc cggtgctcgg acaactcggg tcacccggat cctgggctac tgtcttccgg tcgcagcagg cggctggaga acagtgaacc cttcgcagga gaagggatcc ttccaatatt agggtagtac g ccaa a agt a tgatgacttg gaccaggcgg tcgagccttt cacatggttt cgcagtgagt gtactgggqc tgccaaaatt tat agccatt gcaacggagg ggcgaaggag ggtagagcga ctacaggata atgtatcaag gtagtcatqg agctgggcca qtggaaattt gagcttggca ctccagtccg ctggcacagg gacacgtcgc atcaaaacat ggaattggcg gcattctgtc tcqatgttta t tgga ta cga tacgagctgg ctacaggata cttatactgt atccggggtg gtgtatcacc ggatcctcgg t cattcgttgg cccccgqccc tttctgcctc ccgacaactc tcggqgtggg ttcgccgtcg gqqgctttgc agatgcataa qgtgatqqct ccatatacgt qgattaacca tattqtcatt catgaaagca aaattgtgat 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2501 <210> 41 <211> 3570 <212> DNA <213> Aspergillus niger <400> 41 gaaaaggatt ccgagttatg aaaggggcag qatccatttt gggagtttgg gqccaactcg ttgccattct aactgggtgg tacaccggga ctgattacat acagqtggtg gtccccatgc cgatgtgatc ccaagatctg qggcgaggaa tct cccgccc tcaactctct tgccactttc cgctcctaca cccgcct cat cgtcctgaga tcgctgcggc ataataggcg qqgcctggaa ctaggcccaa aa ggcaa aa a cagggccgcg ccctcgcttt ggtccttatt gaccgacaca acccagtacg gagagagttc tctgggcctc ttccaccacc taacatgatc ccaggctagc gtggatcggc tattagtcta cattcagatt attgcttttg tacctggcgg tgttgqtcca accaaaactc tgcgctgctg tgcatatcca tccgatctaa ggcgggccat gaaaggcaag gctctctttc tcattatttc atccccagtt actttccttg tggcaagcct tcccccaaac cctccgcttc tacatgcagc cgggggccca ctqaggcggt ttggaqtgtc tattcactcg tcttacgqtc Cccttttccc cttctggctg cctacttgqc gatgcgtctt tctccatccc 120 180 240 300 360 420 480 540 600 660 66 /282 catcgttcct gccgacgtcg cat cat acct ttgcgcgatc ttggtcgggc agaaagctcc cagaatgacc gaccccatct aacgtgacgg gatgacggtt tat gact ata actagatgcq tatgatagtc gctgcggcta tatgacgatg ggtatccaaa gccattcatg gtgggtqcca ctggtggttg gacaaqtgct gtggcgctgg attgaggcgg aagaagttca gcagagacct gagcatgaga atgttgaagg cacacccgcc ctcagtacgc agcgttgctc ctaggggcga acgagaccca cccaacgact tctcgatacc gtcggaggtt gagacgaagg ataaaagagt cccaagcgct tcggcgaaca gtatctggct tggacatgta acgacaaagt coogtgaaat gcatcgctgg ttaactacgc gcgccacaat atggtcgtgg acgataactg ttgatcggga cctacagcag cgactaccca cct cagtgt cagtgcctqt gccatgactg gggatctggt tcccacaggg gagccaacct gaggogatct cccggcggcc a ctggtaagt gtccgggatt tgattacttc aggtgctcgc ccgtgaaaac acgccgccgc tctaggtggc gccgccgaca tgcggcgcag atggcatttg ggagggcqtt cagcaacgat accagagccg cggtgcagcg tattcggatt otatoaggag ggaagccccg tggaaaaggc taactttgac gggtaaccat cggcgccagt tggtggaact gcggccggaa tcatgaagat gggatatggt gaagcctcaa cgagcagggc ggaacggctg cagcgtggag agataatcaa aaactttttc ggcaaatgga gctctacacc cacgaaggcc agtgacgatg tccggagatg attctttggt ggatatgctg aaacgcattg tataatactg acagggcaqg cttaggccga aggccgcgct aagaacgacg ototoogcac aacgatatct ggcaccctga tcggtttttg gqttacacca cctccgtatt gatgcaattc t oggcggccg ctcacctggc qatggaagct aaggtcgaca gcctggctcc ttggctagtt ga goatgt ca ttacggagoc gaggtgggct tcggttgtcg ctgtgattgt ttgatgaatc ccgtcggaga tccatgcgct acgccgctgt ccgagaagct ccagatcgcc cctcggaatt ttcagttggg gtgtcacgac actattttgc tgagcgatga tgtgcggggt ccattgatga act cgtgtt c tcaagcgggc tgtttgcggc acagtatcta cggaatcctg ataccacgga gcccgctcgc gtgacgttca ggcaggacac catatacgct attccccctg cgtacgaggt cggtcaccat ctgacggtcg atgttgactg gttcttctgc caaggacacc cacctcgccg attaccctca gctggatcaa ccttccctcc ggctccccag cgtcaacact gggcatcgcg ccatgatctt ggctattgtc ggcgggtt ct ccgccacggt tggtgttgcg ca ctgat gag ctggggt ccc cat ggtcaat tggtaacggt cagcatcacg ctcggcgcaa cgtcggcaca tgcgggaaoc gtatttgatg taagaacggg ggtgaaacgg qcagcgggtt gacggaggat gaatgttaac ggtcagtcac qaccttcatg taatacatat aatgtcaacg 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 67/282 agcatactgg ccgagcagcc gaaacgtggc ccactggtgg gtagtcttac gctcaacacc ccacgttcqg t tgtgttctg acgacagccg tqaacggacg gcgagagcga ggatcagcgg cagtagatga tgaacaatat gcatcatctt taccaaagga ttcctccgca ctcctcccac ggcttttcct gcaatt cat C tctccacccc taccacgagc cgttgatcgc agagcccatc aagtccttct tgcgtcgaag cattggcctg ggatgactac gtcgaaccgt tgaggaaccg cqaacaagaa gggttgattt tcctgctgtg tgatcgggtt a cact aaat t tctcgtctct cttaatcttg agctccacgt gattggcgac atgcctactg atcagcgccq ccggtgaacg gatgatgaag ccgaccaccg cggacgcaag ggcgtct act gatttcgaga tcacgtcgcc ttattcagtg cgqqagggcg tatttcggac tat gctgcat at tat tcttc aagggtcttg cctgctqttg ctgtcctgct attgtacctc tcaacttgtg aacacgatga ttcccacgaa ttaagcctac aactccagaa cgtcagatag tttqgatcta tccatgtqca tgatcgagga ggggtggcga atgaggatqa caqatggaga agtgtttctt agagaaagcg atctgccatg gcgatgacgc accgcccgcc tctagagccc gggcgaggcg cgaccacagc aaccgaqctg aacatccgcg gaccctaqt tatcctgcct cgctgcgatc gcgccgcaaa cgaggatgag gctgtacaat tgaaccgtat gcattctcgg acttqttgga tgtatatacc gtttgtgatc ttcccgtcgc aaccaacctc cccagtttaa attgacggag tatgagqaag cctgacaagc atgccgaccg acagaggcaa tccttcttcc ggctccatca cgtattcgcg ct acaggca a gcttttgcgg cqggatcggg agatgaaatg tgacctgcgt atgtatgtgt tccggaatag tgcttttgac catctcctca tttaaaaacc 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3570 <210> 42 <211> 1236 '212> DNA <213> Aspergillus niger <400> 42 aggtcccgga cagatgacaa ggctctaaga ccgctcttat tggcccggac gcttcacgcc tccgctcgct atcgatgcgg tgtttgcccq cttgtgcttc gcagatccat acccctcaat atgattgtgt ttctattcag agcatcaqgc ttggccgcct tgggtaggca aggcctcccg cagcttcaag tgaagagaaa gaggggaaag cacgtcctcc tcttcagctc acatcaaaca ctgtatgtct gcgattactg ccattgatgg gacctagtat ct cccatgt c ggtattctca aaagaatata tctattcttc cattcaqggt cgcccccgca gaggaatgtc agcaaacagg tatacctcag ttqccatttc agtagcttga actcctcaag ctagccgtgc tgtctctctc tcacttcggg cgtgatgtca ttatggagcc accgctactg caatctcctg agtaaaccac 120 180 240 300 360 420 480 68/I282 tactaccaaa tgaagacctt ccgttgacag atgtctctgg ataagggcta ccattgcagg agacagtcaa ccatgaacac ctgaggtgga gaattcggcc acgcttattt ca cat acgt a tqaaaatgaa cacaatct Ca ctctaccgtc cgctgaagc agcttccttg ctccaacttc ctggaactct cattctggcc cctcaccaac tgtcagtctt atggcaggga gggatacttt catacacata atgagagatt tctatagctc acctctctcc gccggcacca accaccgtct ggctcccttc cccaactgcg attgattccg aaccaggccc tgcgcataaa atggttatag cctttatctt cat caatat a ctaaqgtcgt acgagtacca tcgctctctt ccgtctctgt cctgctcgga cggqctt ccc gcaagtgcta cacctggtgg agcagctgqg cqccaaacat ttggatatga acctattgtt gtgatatatg atctac gcatcactca ctcctcggct ct cat acgac cgqtgccaac caagattgga cgccctgacg cttcaacatc tcgtatcgaa tcagcaaatg tttcgggatt aatagcataa aacttgaata tctaccacaa ctggccgcac actgcctacg ggcctgatca ggcgccccta tacaacqgc gctctggagg gctacctata cttgggggat tacgattgat tacggagcat cagagctttt 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1236 <210> <211> <212> <213> 43 1750 DNA Aspergillus niger <400> 43 gtgaaagata gtgacgctag cggaaccctt aggagaaatc gttgcctttc tttctagtga ctcaaatatt gcaccgaggt cggttgtatt acggctatta ccgactcaac ccactggcag act cgagata tcggatagcc caacagcgaa ccggcgcccc acagccaagg gcgcacttta gcagttccat ctggctttca ggacctgatt cgccgttcaa cccagtaggc aaacgaaacc ctgggagctg ctacaaccaa gtagaccctg cccactggga acccagctcc cccaagt tca ct at tccct t tcactttagg ctcttcctgc ttcccaagaa gccccttccg cgtccaaatg acttatttca ttttggaggc tcctacccct aaagattatt tccaaaacac tgcaggggcg ctgagagacc gttcctatca ccccacggct ttgtctcttg atgatacctt tcgcccataa aaacagt tat gtgtctctgg tgagatggac gqatatcctc tgagcctaag tagatgaagc aaaacatgac gaaatggcgt gcagtcactg tcgttacaag ggtcagagcc tgcgccaatg agttaataca tggccagacc tatcggcaga caattgttca cccatacatc ggctcttgca tattgtaagc tctctaactt gaatttaaat cttggcctcc agcagtatgg gaqtccaacc cctttgatgc tacatcgagt gaccatgtgt acgttcaata atctcagaag gacggtagcc 120 180 240 300 360 420 480 540 600 660 720 780 69 /282 tcaacatcga gggttacctt gcgagaactg ttccacccca atgccaggct ttgagtctaa ctgtgagttg atgctgtatq agatgtgctc cgccaqtagg atgtacgggc ttqtgagcaa cacaaacacg caactacaat caaattacgg tcggtgqtta taggtggggc caaggtctat cagcactcgc cgataaagtc gttaccccaa aaattcaact tatcctggcc caccactgaa gcttgtcatt gactcaggct ggaccatcaa tggaactcca accacgcttt agagqagcgg gcccaacttc aactctcgga gcgcccggat gagggctttc gaagatgcta t cg tct ctt g gaagatattg tcaacttcaa aagatcgcag gaaaccaagg acqctagctt ttgagacagg ccacacatat ctcactctta tcttgaatca acccgccatt agaggcccag tgcttgtgcc aggcagtaga actacacagc qccaacccaa ctctattqtc ataccqtgtc gcccctgcag acaatgaatg aaggcagcgc ttgccttcct tagacaggaa gtccctacga ggttgtaaat ttgcatcctc ccacatagtg actatctctg atggcttatt acacctccaa atacaatgtc cctcacgacc gattgtggac aatgtgccca cgttagcatt caataacgca gagcagccat tttctaaagg aacaggcttt gaccatagct cccatttctc tttagcttca tcttgqcagg ccaagtgcca gcttgaaggg atgaggaatg attgtcgaca ctcaccaata tccctaagga caactcgccg agtcccgagg cttcaccccg gaccacggcc atccaatgct attgtcacgt at caggaa ca aatacatagt attccttacc gtcgcctCtc aggctqgact tttggaggtt cggccgaagg 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1750 <210> 44 <211> 2030 <212> DNA <213> Aspergillus niger <400> 44 tggatgccga gcaaattaat taactgcgct ctcttagcag tggtgcctgg atgggacgaa cgaaactctc ttttacgtac cgtacggcca attaacttac aagtaccctc acgttatgta aaagtctccg ttgtgcgatg gctgttatta aagacgtgct tctttttgga tctttttaca tCcggatttc accagggtgg tgttagtcca tggtcgagat gtcgccattc tcagcaggca tggcgttgtc tCtgggatgg tatgaggaag gatagatact caacaaaaag tcatcctata tacatggctg gccctgggca atatcagtgt gccgaatqtt acttggatta cacattactt ccatcggact ctttgctgtg aatgatgcca agtattgggt tcctaacaaa taqcttgttc gaacccgcaa taaaagcgat acttgcaatt acggcggatg ccgatqcatc acatcctcac tccgtgaaga tggatctgct tcccttggca atcggtaggc tttagatact ggaccggttt tgcatcaagt ctctcgacac ttaacatggg aaagtgttaa gtgtcgactt gttcttatca 120 180 240 300 360 420 480 540 600 /282 tttcgtctcc agtcacctct aattgct act ccgcctcaag tgcatcaacc ggtggagcct tgagcccacc tqatacctat ggcctcgttc cgacatctcg tat tgccatt ctccagcctc cctcattcaa gtcaacctgg ggtgagagtg gtcactgacg acacgaggcc ggtatgcagg ggagaacgaa tttgagtcat ggagtactcc agcggatctt tgtttgtatg a cat tgtt ca atcccactgc tcacccagct gccattttcg gcccgcggca aagaaccaga ccctctgctg gqcaactctg ggaaacgcca gatgcctggt gcaggcgatg attgagaaca ggtggacaga cattaccaaa tggactttgg ttggacttac ttaccatcqa tgtcactgtg gatgtgatga gatgtagata tcttttgatt ataaggcaga gtattccaaa ccagttgtgc gcaagtaaac aatcttcttc tcactaccaa caagcqttgc gcagcaaqggg ccaacgttga cagcgaccta gaggcagtca ttcttcagac atgagtggta agattgttgc agagcaccgg acqctgagtg cgctaacgcg caccgtcacc cgatgcgacc caqcgactct actgacggtg tgtgatcagg qttttgattt gatcctccgg tgaagtacag caatcacgtc tgcagattat gtgattttga aagacttcaa ccaattcttc cgtcgcagct atcccga ccc gtacagctcc cactgcggtg ggctgcatct cggtgttgac cccggattac cattgtggag ccagaaggtg gattgtggaa atcttagact ttcactggtg atcatcgaga gaggtgacca ttqagtgtct tcagcgcttg ctagtactac aatcatatat gtcttaaaac ggtaacatqg taatttgtat aqtccccaag agtccatagt aagaagaagt ccccagcgtg ctccaggcag aactggtccg accgqcacct gcctgggttg ttcaccgtga gcctacgact tcctacacct tccaaggagc ggtaatatga tcgaggaaaa ctgttgccaa ttgaggagaa tcacctacga caatacaaag atttcaatcg tttgcggggc caaqtaatgg ggtatgatcc actactactt aggcattgta aacacaaagc tccaacacac tcactgctgc gcctcgaggc ttgctagacc qtgccgtgct tcactgtccc gtatcgacgg ccgacggaqa tcagcggcat cgactaccgg tqtcqt ccag aacatacatt tggttcgctc ggcgqccjggt tggccaggtt gtaaatttgc cggqttqatt acgaggcaqt ccctgttgaa tgcagcgtag agtaagacaa tcatctataa caggtgcgct 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2030 <210> <211> 3080 <212> DNA <213> Aspergillus niger <400> cttcggctgc gtcatgattc atgcgtcaaa tcagtggact cttagtaggt ggatgtacag cacttatttg atacttcgag tgtccgccaa catccggccg tctatattct ataccaatcc 71 /282 00 00 acattatgcc cagctgatct taccaggcag ggagcagaag accgggtaca aggtgtttcc gggaaactgc agtgctctgc tcctccgcaa cttggaggct cacgct ca ca tcctctagca ggcacatccg aaccccgtct agcgagcgca ctccaggaat cgcctggcag cttcagaccg ctcatggaga tcqgaccgca tgggagacga cagatcatct cgcatcgtct attaccacag gtggaagtcg atcgcctaca gtcaacacga gtctacgaaa agtgactgqg gccatcacac caacgaaact aat at act at aaagtatctg tat tgtgcat tgatttagcc agaaagggct ggtttgttgc tcaggcgtcg ctatgcgctg gtcccttcqc tgtcccgacc ccccttctgt agctctacat acgagtacca atggtgacgg tggttgccac cctacgtctc gcqcgcaqtg gctatctccq acacccaatg cgcaagaact ccaagccata act acgaaat ccaactcgac ccggctccgg ccctcaaagg cctcggcgac agagcacctg actaccgctt agaagcagct qtatgctgtg atqctccgat gctqcatttg ggattccatc ggtatcactc ccacgcttag caggtcgagg ct ca gtcaag ctccctcatc acacactgcq gttgattgcc cgggcagaaa tgccaacaca tqgcctccttc taactctgac gcctgcagtg caccgccaac gaacctcaca tcctgcctgg ggacggacac ctctctctac ctactctctt gacccgggaa gatcatgtcc tgtcaagcaa cggcaccagc cctcaggtcc gagcatccgc cacggacgtc gggcaattcg atttaagcag taaacccaag tcccagtctg tgtcccacta ccccgtccct caccgttcag tgcttaaata ttcagttcaa tcccttctag aacatgggca tccaagagca ggcgtgttca gatggcagta tccccggatg atctaccgcg gaagactccg aacatgaagg aatacaccca tctcctgatq ggcgtaccga gccatccgtc ggatctccga gacacctaca gtagacttcg ttccctcagt gagggcttct ccqgcgtggt tcggggtaca ttccctcagg tccatcgtga aagtgagcaa cagtctgcta cacaggactc gcatgactat gtagcaaagg caaattctgc ccaccgtctt gactcaggat gcctggcggc ttgataacat gcccctcaac tgatgaaccg atgaacgccc tagaatggat tacggaccaa ttgttatctc caaacatctg ccactgccgc gcgaatggat ccttcctcgg ccaatggctc aatggtcagc acgcccatcg agacaggcac acctggacaa acacgaccgc ctcccgacgg agcagctct~a tctcgcacca cgttgaacac ,agcactgtgt ccagggagac gctatgttat ctcaatatcc cccgcgcaag atcaqccgcg ctcgctcgtc atccgggcag cat cccggcc ggtqaaagca tgttcctacc cat tgctcct act cct ctcc caccttcacc cggctccgat tcccaacggc gatccttgat caactcctcc cgccttctct ccgcacgggc tgacttccgt agacggtaaa tccagaaacc cgatgtgcgc gaacggcacc g g gact cta c caagcaaqta cagctgggac ggagcgcgtc aaccggaggc 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 72/282 gacttgcaac gqactgagcg ggattctggt gggagctact aacagcgggt gccgacactg acgcgaaaga ggaqagctca cggccggatg gtctggtcgc tgtgcgctqt gggggaaata ccgagggagg gtttgatgta aaaaaaa ccc aggatgt act atgatgacga aaaaatagta gataqtcgac ccatatatag tcqtctacga cttaccagcc tcgagacgag cqgaggttct tcccgagttt caacctacgg caaccgtcct tcctattcac ggacagatct aggatggacg atggtgatac agaagttgat tactttagtt tqataagaat ccgttgttcg gcttaattca tattctgcac tgcaacgaat tccataqcat tact cctaca ccccagcacg cagctggtca agaagcctca cgtgaacagc ctcgccggat caacgccagc aaccacagaa acgcaaaacc ccgcgtgttg gattatgtgg gttccagccg gaccaactcg ggtggcggga Itacacaagta acttgatctt agcaagtttg tttctactct at aga tcgt a ttgatctttt gcggactttg ccctgcggcg ggcggatgga agctactcca ggcaaqaaag gagatcgggc tgggacaatc agcacgtaca acgagcagcg tctaccggca tat gggcagg atgtgqqaaq gqatgctctg gttttgatca ggcgatccgg ctactccgat acctactact ttgacagaac actaacagcg tcagcgatga agtggctcgt tcgtgcgggc tcaccgaqqa tggtgtatcq tgcgggtgct tgccccagtt attacgatgt qtgctaatga tgtatgggtt ttatgattat attcgatgcc atttttagaq taacgcgttg tgtagggttg tcagtatgga tat ctgtata ctqtcagaga aaagattccg cgaaaccaca cttcggcgtc caccgccaac tggagccctg ggtttqggga ggacctcgag ctctcccgat gtgcacgatc tgcgcatgcg ccggtttgag ggatgcggat gttgttcttg gatatgtgac aagagqatga ttggacgagc ggggcaatta tgaatgagaa gaatqacctc gacta act at 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 27160 2820 2880 2940 3000 3060 3080 <210> 46 <211> 3290 <212> DNA '213> Aspergillus niger <400> 46 ttccaacttc ccatgaagtg at tatttactac ttatcqtcaq ct ccgcacctgt tgcctacagg ga gtggcagggg gggtaaggct at cagactagga agctacctaa ta gcctactgaa tctcaccact C9 ctcaatatcc tctagtqqac 9q gtagtagt ttgtcqaa tagcatcc cccgggtt gggacagt gacctgat aaactagc ctgctaataa aattcaaagg tgcgaggtgc aggaaggccc aagggaccaa atttgccttc aactagtact tacctcaaga tttgtggaag ttatccgctt gcggcacgat tctcaggact ggcttgcagg ttgagctgac tagaatataq gccacctcat atcagcaaaq gcgatccttc aaaccgtgca ggtatatcat tcggccacta 73/I282 taaatatgcg taggactagc ccaatatcca aqcctggtat tcctcctttc aaaataggag gggaagatgt tactcctacc gtcgcttcca tat caaactt gaatccaggt gtggtcctgg tcgtcgactc ttagctttga ccgcqacgag aaggagtctt aaggagtcac tggtggcgga agcggct act ggataaggct cctatgggac ctgtcataga tacaagattc cagcgtgtcc ttttgaccaa agataataac a at tat t ga tcgctgactt ccacacaata caqatqgtcc gtcttatgct accgttgcga ggtctaacgt ggcagtatta ccttgcattg cgttgaacaa gtgtaaatct aagcaactcg atgaattgga cctgccaagg atgtagagcc tggatccgga cccagaatca tccaagaggg gaaagcgtgg cgatactcga agcgtcaaag tatggttgaa ttcgacagct gcacaaccgt aatcctgggt cggagtctgc ggatgcagca gtttgcgctc tcttacatcg ct at agtgat tttggtggct gaagtatgaa caaagtacct aggcctcqac cctcaacgac gctcctcttc atccatacaa ccatctaggc gtcgcgtttg cagcttcaga atcacgttgg tataccatec accgaactga tacctgtcac atattgctac gtgagcatgg ccaagtgcag gtcaacaaca ttactgcagt tgggcaaqgt gatggagaat ctcgtagagc ccgaacactt tggaaaaaag tccacgtttg aacgctgatg ttcaataaat ggcgqaqat c agccctattg gtgaagtcat aggctat tag gccaaacaat ggcgagagtg ggaactgcca aggcaactgc acgataccga tgcctccgga cacatcctgc ctattgttca gtcaaacact gatgtaacgt atgctttggt tqgtgaaggg agatgcgcga tcttcagcgg tctttagata attcagcgag caacacctaa cagaggcaga acgaagcttt ggataggaaa gccatggaga tcccagttgg gggaggagaa cggctatgca attattacgc ttttcgagta ccgaagatct ctgtgtctcc tggtcgtgca ctgagctcga ggccagtacc atcaggaggc aqgaggattt tctgactacc atcttttata tgcaaaatcg caagggaaaa attatgtggt tgatgatgag tctaacgcac gatcacgaat tcaaaaattg tatggtggtg ctgtgctgag cgggaaagct cggaaagtat tttttcctgc gggtctactt tggtat gage attcatgaat gtggcgtgaa aacaaacgtt gctqctatac gcctcatcgc cggcaactgg ctgctacaca caagtctcgt ttctggaaat agctctctat gcaaggtaac gcctccatgc cgggaggaat ccggagctac aaaatct gag agcaagtggt cctggct ace gccattcqat aatttccaca tcctttaaat tctattaggt gcgctcgctt cettggcggt ecattcttet tttcaaatag atecagacca ttcgatgttg ttccctgacc gggagttctg tgcaatcaac acggecceg cgggaaacag gacgccgaga tggggctttt ataaaccgtg cttaccaatt get ggcccat tatgagcaga aggggcccag gtgcctttga ggctct teat gattcctcgt atcctatgta tggaatatgc 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 74 /282 tccggggaca aactggagac acacaatata ccattgctgt ttcacctgat ggcgcgtgga atct gtt ccc gagtggccca acctgacccc gagaagtcaq cgagttccgc gcaqttatta ct gtatct cg aattattcac aggcgacctt catttcttct gccccagact gttcatcacg aagtaaggcg gcgacctgag agctgacagg ttatcgggaa cgtagcagac tttcctgagt caacccatat tccttgtgta ggaactgttt gtcatgtcgc catctgctag atcctttaca accaagagca ctgcactcaa atcgaagcat agaacccgga cgcctacctt gcgttgaatc gttggagatt tggcgctatg tat gcgt at c tacttatgat tttgaagtac caatcgttct qcaagatgac cagcgaaagc gccaggtaga caggtgacac gcgcgtgaaa tcataggagc tgaataacac ttcaatttaa ttgcagacca tgatgtataa aggtaatcca ggcttctgcg tctgggccga at ggtaggt c caagggccct ccagtaacgc agactgacgc agagcagaac taactgttca gatacgccag ggagcttccc agaattgatg aa ggt ta aat tggctagaat attatatcag gatctgttgc acccctgtcc tcgcggtggg tacaaatgcc gtattaccac ggttcgcatg cgaccaacac tcgcaggcaa cgctacggaa ataggcagtg tctgtcggag atgtcgcagc tatttccaga tttcgtcttg tccgccttgc aagtgtcgcc gttaacgatg caaatgttat ctagactacc atcgtcaggg gaagatcatc ggggaaatca cat aactgta tcgtgtgtca catattatac tacatcgcac gtaagctttg ctcatacgat tgagtacctt attgcacact ccgqagagtt ccggatatga attcgctgag agcgagcgct cagtttgccc tgagcaaatc agaattatta gcaagacaga ctaaaccatt ctgaggtgtt 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 31000 3060 3120 3180 3240 3290 <210> 47 <211> 3080 <212> DNA <213> Aspergillus niger <400> 47 gaaaatcccg accgttaggc tacctaatct cagctttagt ctctcgaagg aaaagaaaac agaagtgggg caatcacttc aaccgttcat cgtcggagct ggataaggta gtcgccatcc aagtqtctgc agctagctct attttgttca gtcgccattc gcccactaac aacgccattc ctgataagcg ttagctccga ctccgagtta ctcacgatgt tgatgctttt tctggtatct gctgtcttta aaagtaatcg ctgttattga ccatttccgc gctacgtatc cccacggccg gtcatgcggc ctggcataac cccccgt tag ggagcctata gttatcaagt tgtgcaatgc tgtctcttaa acggactccg ttattacgcg tggcaaagat cccacttacc atattcggcc ctgtcaagtt cgcagcgccg ccaaatggat gcgcaagggc cccttct ccc caggctgtgg 75/282 tcataagagt tcttctgggt gtccaagttg aatagctttt ggtgtccgat ggagaagtgc caattactga tgcgcctctg tgaagaatta gagttggaac atacgatgtc ttccggtcjat tgcaagccag gcatttcgcg cagtctctgg acagcagaat cgacacgctt tact tggcca attcagttca ataactggac aagaacgcga ttgcactaga acga cat cgc cgcaggagtc ccgtggctac ttggctacct cctgcaattg aatttgccga gccagct ggg accagcctgt atcattgcct ctagcgaccg catgagaatg atgctcgatg cttattcggg aggattatoc gcctcaacca gccatctggc ggtccttgtt aatgaagtca ccaacaaatg ttctccattg aagcttgcac caaacctggt gctgaaagtt gacaaaatcg ggcattgtga tacaataacg gacctacggc gcatccagga ttccggcttg atggggagat ccatcctaag cgtccttgcc acagttcata cctcgacagt ggtcgggggc cacgggatac caactacagc cgcogcgtat tcagcttctt ctcaatttcc tgactatttc ccgtgctgat ctatgtacac tatcaacacg gcttcttttg tcaatggcgg ccattgcatc atcttctatt gcactttggt atgttcccca agacagctaa ttttcgagtt acggaggcca cagaggggac acggcttgat taaggctcgc ct cgaaatc ggctttcgcg cctcacicag ggccccatca aacgacccat gctcttgggg aaaacctttg ggtgtaaaag gaaaaagcca tccccactcc ttcactcgcg gagatcttca cgccatgttg tcccgagccg tttcaaagag tgtcagcctg cttccccccg taagccaatc gtttttcgaa tccgggtggc agactccaag ccttgaccag tcggactgcg gtccaacttc tgggactgca cccacactac ttatggtcca tgcagaagac ggatatggtg ccct tcttca tcgataaacc atcaggccct ggaaqaatat cctactacca tccctgccaa taccagtcaa atatcgtcca tacacatgat gccttgcagt ttacgcccga tcttccaagc tgcgggcgac agtagtctgc gaaggcatca gtgtgtgcag gaatttgcga gtttcctttc tcgaaacatt gcccgcaaag tcgtcgctca accacagtcc ccaactcaag gacggcqaag acccatcatg ttcgcggctc aagccaaacg ggcatctttc ggtgcacagt atccaagaaq ttcaactcgc oct ctacgaa cgcctgcgaa ctctgaaatt caccttcaat gcacatgctc tttcacatcg cggcgqcttc gtacggagat tccgtattcc cgggatcagc cgggcat gag attcaacaaa tgcttggggg ctgtgctcaa agtatctaga aactacgccg cgacgggaca ggaggat gag atcccagcaa tggggct Oct tcaatccttg tcggcttctc aagagatagt ttggtacctt acgctctatg atgatcgtgt ggttcttcca atttgcatct aggcttacat gtaatgccta gaactgatgt gcggctttga tgcggaggcc cgcgggtggt ggatatttga tcttcgagtg ctggatgcaa cgtgattacg cgtatcaccg ggcatgaccc gtcccct cot gatatcccta 540 600 660 720 780 840 900 960 1020 1080 1140 12100 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 76 /282 00 00 ctggcctctt tcaagaatat gtaccccgga tcgtggatga agttgtagta tagttgagcg aaagtggacc gggccaacta atcttatggg gctgcttttt agatcgcgta cctatggcct cat catatt c gaa-tagagac ggctgttqat ccctcctatt ggtttgggag tagcgcgggt gcttagaagt acatagtct a aatcaattgg gcgcccctct tcttcaactg ggtggattca gatggcctca ataaacca aattaaattt ttcttgcaca gacgaattcc atgccaaa gc accgttttga gttgaggacc ctaccggaaa ctctctcact aggaaaatat gaggatgatg ca ca aat tag ttattagccg aagtgttcgc atttcttcaa caaaacatag agtcggttgg cgcagtgcta acggatccgc acgaggggtt gccttgctag tacgaacacg atccacgatg gtctagtctg gcggaggtcg ttatgccatt cagatttgat tacaaagata cgagacatta acctaaggat tgttctaagt gacggtaaag cagcattctt ctcttaaaat tgatgaatct gt cggacggg caggatatga cctcaccgaa tact aaaaca tgagggctac ggcqaaacat agtattacat acgtggcata cccggcacgt gattggtatg ggaggggatg acgacacaaa ctccagcaat ccaacgaaaa gattgttcac agagacgtaa ccqcagttcc ttcgcccaag gttgaaaatc atatttcaat 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3080 <210> 48 <c211> 2520 <212> DNA <213> Aspergillus niger <400> 48 tCtcgcctgc cgcttcccga gcaatgattg tcttctcctc Ctcggaatcg ttcaattgca agagcacacc Ctttccagct ctccagggcg aaagttcgcc cgtccccagt gtagatcaca aagcccctgc ctcgaccttc ccgccaaact cgcaactctg attattatcc aagatgacca gcccttagca gacggctttt ctcaagttcg gttcaagttc ccattCCtcg ccccgtcttc tcaaccgatt tattcaccgc ctgctatggc tat caacccg cgataagata tccgattcc ggtttcaatt tcccttcccc gtccgctggC tagaagatgc cgaccgcaat acttccagaa atggctccat tggtctcgtc gcaccaggac aattctttcc agcgatacgg accccatgtt ccagggttcc gcttcccctt gcagcagatc acccaaggtt ctcgttcaag cgacgactac gctcctgcag ctaacgcaat ttcaccctca gtcgtgccca ccaagctgag agaggggaaa ttgacgtagc tgtcttctgc gtcgcagggc ctcgattctc gaggttcctg tcgcgccaag atgaaggatc accctctttc ccagccactc atggcacaga tcaacgaccc cggttccatc ggctatcacg ctcggccctg agaaagtgct tgcttgcccc tcactttcgg acgatggttt tcaatcgtct cctacgacga ccctcacgta ctacgcccgc tgactcgctc tgccgactgg 120 180 240 300 360 420 480 540 600 660 720 780 77/282 acctatcccc gactgcaaga tgggagccaa ctcggcgccg tttatcctcg gtctacgctc gtaccaggcg a tcat ct at g acccgcaaga gcctccgccc ggcgacaagt gtcaaatcca caccaaaccc a aat at a acc aaccacctca gacatcgaca tctgtcccta acggatacga gcgggtaaag gaggcgatga aacttgtatc ctqctgcgtc actct cctac gcgccaaaag tagctccagt ctttacctta atgaagataa gagtagccat ccttcgatgg acgtcctgat cccgcacagt gat coat cgc acgaaggcgg tccccggcgt gccacagctc agctagaacg tgctcgaatg tccaatcaag tccgcttcat acgctctccc cagacgatat tctccctcac cccttactac ccgacgccgt gtctcgaggg gattctactg cgctgaatat tgctgtatta tctagatctt ggcagctgct tctttagqgt ttcatgtctt atatagccaa tactaggqgt ttatgtactc aaaagcaaaa ccactacgac cggtctcatg cgtcctggcc caaattcctt catgggcctc tggcgaaaag cgtgccccct ccaggacctc ccaagtccgc cgactacatc cctccaaacc cgagaaaatc caagaaccgc ggccttcccg cctcagcqqc ctgggcccgt cagaaaggtc ggctttgtcg tcatactgtt cggtatgcat attcgctctt gatgatgaac ggctcaggat tcctggagtt atgcaaccac aagaaagggt gacgttgccc cgaaagtggt ggcgaatggc tccgttgttg ttcggattcg gagaagaaat gaagttctag qgcagcatcq ccacacacgg ttcgtccccg cactccccct tccctagcag tcccaagcaq aacgccctcg gct gtggaga gaaagcgaca qccctcagtc ttctcgggcg gtcgtgagcg aggaatattt gatgagagga ctctcctttt tcgatggacg ttgctcacga gaatgatggt caacgagaac gtatttgtct aa gaa aa ta a aatgcactgt aagaagacgg tctggggccg aagacctact acgaagaatc acggaccgga acgacaacaa acgttgtgct gaatcggcat tcctagacac cgcaagtcga agaaactggc cggacatcat tcaactaccg tcatctctcc ccgttgaccc ccgccccggt tcactcgctc gcgacat cat acagqtggag tcgatattga atggatactc gaccgattca cgtgctgtga tatgaat cat cagatctata atcgatctga aataatattt agcccctctc gggcaatatc cggtgccagc ctcccaaaag ccacggcttc cagcttcgaa caacqgcgtc cactctggcc catcgccgag tcaccacccg accgtggctc ctcctcqcgc caacggcggc catcgctctg cat cgt caag ctccctcaac caqcccaacg ggt ott cgaa gaccgggaat tccgtcgagg tat tcat c tt ctatcagact tctgtcattt gtctgtagga gtggtctact tttccacgaa cagtctaatt gcagcggcct cctgtaacag cctgctttag 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 caatatacaa caatagtaac aatcgagagc tcaatatgaa tgtataacga gtgacctgca 78 /282 <210> <211> <212> <213> 49 2730 DNA Aspergillus niger <400> 49 tttagttgtg atctcaatcg ccatgtcagc gaccatgtct In aaccccggtc attcactagt tcctcggggt ggcggatgga oc gactagqttt cccccttgat Scagcgcgtgt tccgcaaaag tgacgcagga tggcttgctg caaggctgag cagttctccg tgatcccaga tccatcgttt cctggcaagt tcctgccccc agagcaccac tcttctttcc acgagcgcga tgaacccgct ggtcccgtcg gaagcgatcg ccgagtctca aatcagggga ttggctacac gatgaacctc acaccggcag caqcgatctc attacggctc ttacaactca atatccagta tgtcgacggc tctccaatgt gactttgacg gtaagtcttc gctattccct agggggtcct cggtatcgga gtgaatacac caacttcccc acagtctatg gctcgatgac acaccgccaa gtactacggc acgtcgagtt cgcggtcaac cggtcaacaa cagcgccacg tgacctacat cccgacctcc caaatggaca tgccaagagt tcgagggagg tcacttcttc gggattcgtt caacagccca ttaaaaaaac atttccccgt ct gcaccga c aaattacgtg ttggcctggg actcttcagt acggcctcgg attatgacgg acactcggca tgggtcaatg agcgcttctt agtgaagcca aactttcaat cactttcatt tacgccagca gaagccctcg ctcgacgaag agcctgcaga ctgacggccg caattcccca gccgcagcca ggagatgata catcatttcc gaatagtctc atttgatggt qgttttacca agggtctgaa tcaggaacag gcccctcctg cat ataa gaa agacagggaa ctgcccagtc tcaactttga ccgacctcgt tcgctaatgc ctcccggcca gggccaactc ccacctacac caggcgacta ttgccgtcqc ttacactttg atgaagccag tcgatcaagg gaaaaggcac ccctgcctat tgcaccttga tccccgccgt gcatctacga ttcatgtcat ggtaaaaccg gcaqgtctct tgcctgccaa gacagagcct ggctqacatt gccaagacga cgcctcccat gctccgcacc ccatcacagc cgcctattcc acgtcgtcag taacctggta aggtttctag ggaagtcagt gtccgtctgc cttcgtgaac tgtcaacgat atatgacggc ctaacggttt ccaggccacc cqcgatcaac cattctgttc cgtctccatc gaagaacggc gctggacagc gqccgtcggt aatcagagtg acggaggtaa tcttctttct cgacccactt cttcacagcc ggagcgggtc agcgaccgcg gggcgacttt cccaaactcc aacaccatga ctctct at cc atcgccgacc tgttcccatc gctacgaatc gtgacgttgg ccctgtaccg gatgagtttt actctaaagt gactccgagg taccatgcag gtcggtggtq tggccgqcct gqcggagtca gaagacatgt aactccgtct ggcacqgccc gcccaatacc 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 79 /282 tgagcgagta cqggtacgga gtgatcgagt gcgacgtcaa ggacgaagac ttcaccttcc tgttcgactt gttccgacat ccctgctggg agatctccct ccggatcgga ccacggcctc ttgtctcgct ttcacgttgc gaaatgtttt aatgaaaatc gat cggcacg ttgcgactac cacaccgatg ttcctgtgga atccttctga ttaaggtttg ttcctctact cgatgtgaac tggatccttc gaccgacatg cgataccttc ggccaaggcc tgccgtgccc gagcgacaag ggtggcggga atgttgatga ctgtttttag ggaatgcaag aagccagtaa tactaatttt atagccaccc aagggtggct cctgtgaatg tgcctgtcag ctgaagtacc cggattgaag aacatgagcg aacgtttgta ctgcgcagcg aacttcaacc aaggcgacgg tcggacaagg gtct tggtcg taca ta cca t cttgat at cc atctgatcga toga caacca atcatatcat gcgaccggat gcaacctgtt atactgggat cot cgt caag gggactcccc agtgcccggt ttgacatcag cgtttggcct catacgtcgt ccggcgagga gggcga cggc agagttcggc gtgttttctt agatttgctt catcgcttca atagttgttt atcatacatt gccgttgtga aatcggtaac tgtttoagtt ggtgacgtag tccatcatca gccagtattc cgagatgatc cgcagtgatc ct acgatct c ccacgtcctg gaccggcgcg tacagtgccg ggttctgtaa ctaattgccc ggtttcagat cactgccgcg gtgatttccot cctatcctac ctgccaagag tttgtgttgc tgaaaatgtt tgtcttt too gtttcgccaa ctcgaggcca gaaaatgagg ggaaacaacg gagatcggca gcagccacat cgcagccaga atatagagat cttacatctc atggaaatga tggctgqtcc gtcaacotcc toggtgtcoc tcgaacgqct agaattgact ggtqgagcga ggactatcac tcagagcatt 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2730 <210> <211> 3231 <212> DNA <213> Aspergillus niger <400> ocgacgcgac ggcattagtt cctcgatagc agctqoagag gagctttctg tgggctgacc cacccccgca atcgcaagac cgcctcgaca accagcctct cctccaatca aaccatcgat ggtcgaatgt cgcaattaat tctcgcatcg ctotgcggcg ttgttattta aatccgttgt tggtcactat cgcgctggtt caacctcaac gccattgcgg ccttgtccga tgccattccg gtgggaagac agtgcctatc ccgt coat cc gtgatattgc tccctcactg tgggaccttt atgttggtcc" acatccatca catggagaga agcaaatgga aggcaccatc tagcggcggt caagggqccc cqgtcatcag gtcagcttgc agcatgtcct ccggcogata oacgcggtga gcaacggcaa qagaacagca actaccagag ccactgtgto cctggctctg gcacgagaaa 120 180 240 300 360 420 480 80/282 cgtcacaagc ccqcatccga ctgqgtgaa cctatgcgca ttggccttgc ccagaacaa gtgtgagtca aaatctacct tttttatgc acctcgaaac atqctgacat gagattggc ccagtactqg tcggcagacg agqtgcacg ggcagtgaga gaatggcttg tcgcctctg, caacaagggc tggctcgcgt tcgacgcct, ggaattccac gagcacgaga gcgaccqaa( aqaagattct tctatcacct tccatgagti ccqaacacat ccagaagcac atcgactacz tgaagaggac caacaaagtc aagcqtgctt ctgctgccca aggtccgcag ccactccccz gcggctgcgg ttacaacatc accccctcgt ctaagacggc gaccccgaac aacagcctgq agtccqacct cgacctcttc tataaggagt ccatcccagc cctgattgat qgcqccaatt cqggtgaatc cgacattgac attgacatgg cccctactga cqttttqaag ctactccctg gttqacgacc agctctacga accagtcgag ctcgacgctc tcgatggcgt gagtacagac ctagtcctac tgcacctaca gcgcctacgg cgtatacccc gacacccgcc ccggcggcta catacaatcc aacctaacac accaacagga aacgtaatca gcgcctccta cqgccaatcc cgccaatgca atgaqttcat gaagctcggt ggcgactacg gcgtcgcgtc tttcqccgqc gagggcaaqa tcttcaaccc ccagtacccc ggtaccatgc tgtacggcta ccagaccgtc cttggcggaa ccgcaagtaa Cttcagcact ccggcatatc agtttgctgc tgtggagcaa g ggtgcgcgc C ttggacaag t atatgccta g cagatcgga. a catcttttci g tatccatcc( a cgcccatgai 3 tqctaaqatc a gctattaatc attacccctgc ccca act agc iacaaqqccae gtatcaaggc gtctgtacga atgcgccgtg actcggttcc cgtgagtcat ctctaccctc gtcgacacaa ctcgttctca cgagaccggc caaaggtacc aagctccagt gaagccgacc ctacagggac gacggtgacg tccaactgcc aacgacagcg tctggtggct tacttccagt g ttgagagcga g gctatgactt g ttttaqgatc c cccaagtctt 9 ccatccgagg 3 tCgcgggtgg a gccqaqagqc aggqttggat ggaatctaga Iagtgaagctc tcactcttcc qttcctgcct cttgtatcag gcaggqtqac ggttccccag ttcctacagc ttctgcacct1 agcaggtgac ccaatctqtt c gtcttaccca g gatgacccqt c tacctacacc a qcggcgtcta t tccccgtcag c actccatcct c agaacggctq t cctacgtcac c aqagcgtcat g tctcgaatta c ctgcgaacct qi tgcgqtcctg cctgatggaa gcaatggatg ccaaatacqg aggctgttga tgcactccga tgttcatgac qcgaccagta taccacgtcc acccaggtcg aaggccaagt gaagacctcc atcccagacg tactttgcca ggtacctatc tccctgaaca tgtcatcaga :Ctctaccag aacaccttc ;ctaacaccc .gatcgaccc cctcttcc aagcccact tacaccaag ttcgcgtct ct cggccca tccgttgga cacgttaac ttccccaa tcgtatccg 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 81 /282 tattactcgg agtttgaggt cgatgttaac acgaccaagg gtctctacaa taggcttggt cgtgcttatc gattatcatt gtgagctttg gaggaacgct tat ccgcaag tttagtgcta tgatgactat ggagctgttc tcaagctgtg gagcatgaat taatagttca ttatcgtcta aaaataataa ttcatacctc cggatgtctc ggtatggatc tcacccccca tcgctatcgg tgctgaacga ttgaggqgta agatgggatc ctctctttgc tatatatgtc ggccaattat actacagaga atgtataata accggtacta ccgtccatgt ggcgaatgga gagtttggcg ttactaatta caagggcccc tatcactaat agtgctcagt ccgctagtgg cttaggattg tgatggggaa ctcgcctgtc attcttggat tcatcaaata tgtgtcgaaa ccaccaaatg g cgca t ttcc tcgcctttgt ttgacacatg gtgggattcg ggtactaatg acttggttct tttgggtacg aacggtgctg atatttacga accgtgaata attgtcaaat acctaaccca aaaggaatgt cacagcgctg gcgcttatat tcgcgtcggt gctgaccqac tgaatcccgt ctgggtgtgg gtcaggaggg cctaactacc tgtcagaggg tcataggata aggtcaaatg gttgactatt agggatatca ttgtgaattt gtcgaatccc ggatggatac tcttactttg ttagctcaac gctttatgct aact tat ggg gtgtgctaat cattgatgaa tgataggtgg atgtgtcgac tagatcgqtt cgctgtct ct aaaacataag tttaaaaccg tctccgaccg 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3231 tqtcgtatag tcaacggaga tattcactga cttggaaatc ttgctgttgg t <210> 51 <211> 266 <212> DNA <213> Asp <400> 51 tcctgagcaa ttacctcatc caqtatccat ccccatccgg ctgaataggg gggtccattc acataaa tag agtgagttct caattgcttc ctgttccgcc 0 ergillus niger gcagctaccg atctaacctc ttgcctgcag ctttccgacg agagtttttt ttgacaatgc ggaccacgca cttttcattc attactactg ccctctctcg gtaatctgag gcttcatgat atccgatgct gcctcctctg caatgagccc tgcctaatgc tgccccgacg cattccgaag gtcggctcgg cat cgcagcg acctaatcct tcgcaggcgc tccaccgacc catcccctca acacgcagtt gcagaagggc atgtatgaat ggagaatcac ccaccagtct tagcgtctcg ggtaagtgga tttccgcgac accgttactt caaagcaagc a cct cgctt c cgtcatgcgc tgttcaaact cagtatgcgg ccaaaatcct ctccgtgccc tcgagttcat tagtcgatgc ctctccagac ggagacctgc cgcatgagat ctggagaact tctccgccca gttaccacgg cat cgt cggg gttgagcgcc 120 180 240 300 360 420 480 540 600 82 /282 gaaccaccga ctttgagtat ttgactaaca agactqcaag tgcgtgattc cgttttttaa ctaccgcat ccgaagtcc gcaattcta ttaqtggtc ccatctggc gcccattcc acctcacca cgaccgtaa tcgacacct tgtacgtcc( tgaagggtai tgtttccctt CCccqgccgt tctcctacat tcacctaccc tctgqgacga tqatcgactt caaacaacta actccgtqtg ggggtcccct tcgattacct gtaagcaagg tggctgagct acctgggtac atggtaagtt ttgcttcctc ggagttcCtg tcagcggatg it tatcgttct a tttcgacqt g Cctattctt g Ctctgtttt t caacggcgg t ctggcagcc a tgtgqttta a taacgagga t cgacctgca, 2ctacattgcc ccagatcaa( catatacctc ccgccatctc icaacgccaaz accccccaqt agtcgtcatc ctgcccctac: cttcaaccgc ctcggagacc acccaqcqtc cctcttcttg gttccagcgt gtactggggc agcgcatacc tattatatcc ctcgtga tag ctcggtagga acgacaaaaa :agatcaatt .c ggcgagtcc: c tggttcttc: t tccggtcat c cccggatgt t ggcacttac atcgaccaa a gacgtggct ggccgcaagi 2gatgccatgc gacccgtcc cacctccacc ;aaccactacz igccgacaagt CCCttCccca fgccqcctacg ctctqgqacg tccgacgtcc qtcatcttcg atcgaacgca aacggctcgc CCtcccgtgg gatgagcctg gagcgcgggt ccttggaagc aaatcccgca ttagtagtct :g9 caggattcct :t acgccggcct c cctcgcaaaa g cgtcagccag a gctccctaga a agcccgttcc c ccgccggcac g cccagttcaa g tctacatcac tqaacgagga i tCaacagcga accaccacca iacaacatctt *gcggctacaa *ccgcccctga acatcaaccc tgctcgCtt agaagatcct cgaacggcga c ctaacaacac t tcgccacaat c aaccgctctt c acccgtataa c tgactttcag c: ggtatgatga a gtatgttcct g ttcggcgaaq gi ggtcaatggc tctccccaat tccagaggcc ctaacaatta Cggcctgctt taatccatac aggcttct cc cagctggttc cggtgaaagc ggatacaacc ctcggtcatg ctaacaacat ccagctaaac1 cgccttcctc aatcaccgaa ctgcttcaat t CCCtCCCtc 9 Jcacgtccct c: ~ggcagcgac c :atcatcggc c :cagaacatg a :gtcccttac c Cttgatgct g tcqgtgtat ti Cgttagaga g1 gtgcggctt a ggaactata cc acaagcatcc acgcccactg agcgatgagg acaaaqatca caagagaacg tcatggacca ccgggcccct aagcacttcg tacgcgggca tacttcaact atgtactgta cacccaccag tccactttcc jacaaagcca ;actgccaaq actaccacc CCtCCggCC *caacqgact ccagctcct acggctggc cctgqaacg attatggtc gcgctggat tgtctggtC .gctgactg cgccagtt tcttgatt 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 gatgatgagg aagatgattg gatgctttca gatgggaatg cgtgcatagg agatgagatq agatgatgta tcattgaggt gtgatgactt gtacatatgt 2400 83 /282 agatcggtag taaaagggat actataggat atggtatttq atgtatcatt tatgtacacc acgtggattc aattgagggg agcttcaatt cctggttatt acttatcata tttccaacat gtccgcgtat aaccggtaac aactaacggc ttcatgtttg tcaagtgact gtcttqgtac aatactactg tttctatatt ctactgttgg taacttaatc tggacatatt ctatatccac gtacagattc tcgctagatt 2460 2520 2580 2640 2660 <210> <211> <212> <213> 52 3150 DNA Aspergillus niger <400> 52 ccaatcaacc aaggtacagc ctcttatgca ttattgaagg gcgggataca taatctccgc tgtgggcctg tgagqatggc gagtggcttg tgactaaqtc gttgcccctg aaggcagtta tatcaggtat at act ccgga acgccgtgac ttccttgatt cttgcatgtt gaatcaatca cccctcggtg tcttatctgc tggagccgtc acggatgatt act aqcgaga gggttcggct agatcctgag acatcgtttc cagcatgtat ggggttttcc atcccccacc tggtgcatgt tgtccttgca gctgcactta ccaaaagcgt aaagaaccag tatgtcgatc ccqgaaaatg gggctttttg ctgacgcctt tcaatcagta tgggtatgga gaagggttct gagaacgcct *gggttcaggt caatgtgtta ccat cct ccc ctgtttaact cacacaatag cttctatcca ctcaaacttt cat cggt ctt atagatttaa ttgaacaaca gttgtgctat ccactggcgt gaaccqaagg tttcgccaga atccagtgac aaggttggcc cacaacagag ctcctggaac atattgctgc cttacagtga cctttgctgg cctggaggca tcgctattat ccctcttcct gacgcctcac tgcttgtctc ctggatatga gtcgctcatg ttgctgaccg tcttcgaggg caccatgcgt gcccgagaat caaatcgata aatttgtgaq gtcgcatact tctgtggctg aaatatcctg ttgggtccgt gaggt cacca ct tcata cat aaccgaggcc agttcagggt cggagtcgga tggcaaaatq atccagtcaa cgatcaggcc ctgcqatctg attttcctcc taacqatqta ttctccttga ttattaacta ggctctcggt gaatggtcat aaaaccccaa acaacacctg ttcttttggt aatggtggcc acggaaaaga gtcacatcac atcttctttt cctgagtaca gggtccttga cgatacccag cattctcctc ccaaqacact gccgcgggat tccgcctcgg ggaaatggtq cat ggcatgc cctcacacca tataaagccc agaaattctc ggtatagctg tggtgctctt ctacgataag acaatgtcac gggtcaaatc ttttcgagtc ctggaagcga taaaattcag accagagtac cttgtctcag ttgcttacgg atccatttac ttattgatgc aatgtcctac 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 cactatcatc ggtaagttgt ccggtttgac tctcacctaq 84 /282 tttacagaca agtggcctgt agttacggag actatggacc gttcttcaat ccaactgaat acttagaaat taggcagact ttaaatacac cacagtgtac tgcttcgtgt a Qccaat at a atgatgaagg cgtggcgtgt ttccgaacag ttgactacct agtccagcgg tcattgagga atgccgacta cccatgcagc acggtgagac aggttccata gggatattgc aggctacaca aggattgggg cttgtccata cttttatcct acatcatttt acttgctgat aatctgatca cgaccgatat cgcagctaga ggtgagtgca agcggtaggt catttctacg tttaactccc gcagctcgcg actacgcaga gtacatcgtg aactatatga aaattgacca tgcagggaca actttgctaa atgatattcg ggacactgct caagaaagac cgaagt atat cctcgaagag tatctgtaac tcagttccgt tcgcgagtat ctatcaaccg agcgggtaca cacggagtcg gaaatttttc acctaaaaga accactgtgt gcagtgacca ggcttacgta tggatatcca cqctgcacgc ttccgaagtc actttcatac tgtcttttct agcaaaattc tcgggattat cagaggctgc ctttgccgtt gatttaagat agttcgccaa ataggacctc atgtcggtga gctgtcatgt gcacccctac catatgtcaa tcagtcatgg tat gcattcc atcctccaac tggttcggcg gcagcgggat ggcaactttt atcgcagcgt actcagattt ttcqgccac cctctttggt gtggcacgga ggtcctacca taaaagtcat attgtgcctc gcggaataac gcaacctggg aagtccaagg cagaccgacg ggttgcacac gaagatcgct caacggcatc ggcctagaaq aataatacat caaccgtgct cacgatgcca gctttctgat gtggttctac acaqaagggc aatgtaagtg cgtagga ccc atgctatcgg agcagaccgg tccccgtacg gtcaggccat acacacccat cgttcacccg tgcagctgtt ggcccgaata tgtccacggc atgqctaatg agctttccta taatgtcatc gtcatattaa agcaggatgt a caa a agaaa aggtgcttca agttcaacct taagctgact atattgatct agcggggaag attgatgccg gacatcgcta atggaatcaa catg ct t gct aatggatgcc tatgctatat tgtttctctg ctt act acca qcaaggataa gaccccgccg cgtggacatt cgactttqta cgtgtcgttg ctcactcgca gacagtagat cgtatatcag caaccgt act tagcaccaac gtcgagtacc ctgtgttatc gacatgcttg ctaaacttat gtccattacg cgtgatacgc aaataaacat gggcttcctc gtggacagag tgatcaagac aatgaccgaa tcaatggcgt cgattcaggt aagtaattaa agctgtaagt aggtcaatga aggatcaggt gtacagaagc caggggtgca gtttggcggc ggat tgt act tcctactttg aactacaccg tggccgaatt atctacggcg gttaactacc ggggtcgaat gctgggcacg ttatttggat gggacatcgc accgtcaatt cattccgata ctctagtcaa caqqtgtctt gtagttcgta tccaaaaccc aaccaaccac 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 /282 caaaatqaca gaggctaatg cctggacaac <210> 53 <211> 3221 <212> DNA <213> Aspergillus niger 3150 ccatcagctc t gt t tgaat t gtaagatgct cacacccttt acgaatcctt Ct ctcagatc tttccctgct ctgccactta aactgataac ggttgcacag gattcgtcct gttgagatag atatcttaac cgcctgagga agcaagtgag tatgtgacca acatccacct aaccata ccc atacatcccc tatttcaaga cctggtcgtg ttagttatga gtattagtga tgccgagtca gggttgcgtt ttgttgttat tcagattggc tggaagcgtt taccgtaatc gatttgtate ctccgaacca gaagcqtgtc ccccatacat cggcgatccg ttcactagta tctctttttc accaaccacc tacgaqcact totca ccgtt aaatacacca gcccctcggc ccccccacac tat caat acc act caccatc gaacgggcca gaatgagtac tqtgttgaqg tggtgagagg ggatgtgcat gcaggtttgg gttttatgtc atagtgtaat gctagcctta gcgtgcgtgg Icatggatacc gattttgagt Icgacagcatt itgacacccga aaacagtaat ataaagtgaa cgctaccgga ccggcttatc tt tat t act a tttggttaat accaccatgc actctcacct attcattcgg cccttctcct atctgcacca acccttacca tttttctgqt tggatgaacg tgtactgtga gtcgatatqt aatgggacgt gatqgagtag gggacggtga ttgggtgaat I tqggcgtctc ttgacaatat gtgtagagtg tcaccatcga gtcgatcgtc acatactttg gagtggagcg ggcqatggcg agtacttcct tgaactactc Cttttccctt ccctagtcgc agatattccc ca at cccaat Ccaccccctc atctctccatI actttccttc gcgggcccggc atacggactc g tgtatattga g gacagaatga g )tgggacggt t :ctctgaata t gggatggata atccctatgt cattgcctta gccacctaca gcgcctgaac tagataaact agtgcacggc ttatcaqagg tcgccttgct tccatgagag ttcgtccgct aggacagtat tggtgcgagg ctaacacccc cacccccaqcI tccaggaatc :Cgccatcac ~ggatcctcc z ;aattccacg g ~cagccggtg c agtggggag a 'acgtttttg g aatggggga a gtttcttct g ctgggacgtg ttctCttctc attagaacct tcatggcgcg caaggctgat cggcaattaa cat caag tga gaccttagta tattgcccat ttctgtacag cttct cggct taccctccga at ct ctat a atactaatac tactccggct agcatctcgc :ca aca a tg ltgattgggc ;cctataatc :agacgggat tagatgtta tggggacqt gggcgcttt ttgacggga 120 180 240 300 360 420 480 540 600 660 72D 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 86/282 atggtggtgg tgatgacagg gtgaqtatat ggacggagtc atatggqggga cggtatggac cggcatacac ccgggaagaa tgcaggtccc atcgcacgct tgatcatcga agacggtaaa tgtatacgaa ctct cgtgcc tcccggtgaa attatccgcg gtgtcaaggt aagatgtcag ccgaagtgca cgttcacgcg atgagatttt agcagaatca tgccggagag agcagaggga atattgaggc gacattqacg taaagttagt tctggctagc ttcagatttc Ccggccggac acgggttgac tgcggtcaac atcagccctc ggcgctcttt gatccatttq ttcgttccct ctacgaccqg gtgtcgcgat tagcatctgc tacctccggg ttacttcgtc ctataccatg aaatgat ccc qgctatcqgta cctgctggtg gacgaagtca tgtctttcag taatcgcgct gagctatggg ccctgagccg acgggtgctg tgaaaqctcg ttggttgcca gcataagtgc tcgatccggc cat cagtcca CCttctatta ccctccattg gtcacacgtc gtcctcacac caggagatga gatacgctgg gagcaggcgt gctatggata gctggcgagc gaggaggcgt cgaggatact gggttcttga tcqtcagagg cgcggaatga tatagggacc gagtacgagg tcctacgttg gcgggccatg cagtttaatt acggaqggac acgtgctatt agtggggatg ttcagcggtg tatgttgaca atagctgact aagtggccgq tctcaatatc ttaacaqcgc cggccatcga accgcaggct ctggctttct atgagaggat gcattatcaa ataacaatac gttggagcaa tcggagatcc cggactactg acgacatagc atcgcccatg cagtggggaa tcggggatat gqcjactatgc atgcggagaa ggggtctagt aggtgccatt gggatattgc cgtcgtcaac tgttggcgat cggtggtgag ttggtgatca gtgttggtgg aagaatgagc ctgactgcct tccatctggc cgctatcacc accttctcga cacctgaaag ccgctaatcct tgagagtggg tgqgtgtgtg gtatgggatc gcctggcgqg cctcatgtat ttcgcggqag gcatttcacg ggtgcaaaag cagtttcgcc t gg atactt g ttgtccgtgg gttccgtgct aaggcagtat ttatcagccc gacgggaggc gtggcatatc ggattcgact gqattgggtt gctggcacag atgaaagtga atcattcata aaagtggaag ttgtcaaact cggacaatcc accttctatt ccgccggcgtt :ccaagtaca c gaggtaagca gatttactcg gagggaatca tgcagggata ggcgacaatg atcaagagcc ccggatgcag gcacttgggg tcgacgggcg cttgactccg cgcggcgggq gctgggtatg gggaacttct gaaacggcgt atttctctgg aaaaacgaag tgtacggatg gttgttgatg gtccctttgq tatagatgga tatggataag actggaagcc cctatatcca 3tatggcatc 3gtcgaccgc gcactatac ~ccttcactg 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 tgccttgatg tcttgaatca acatctataa aaactgcatt a <210> 54 3221 87/I282 (211> 25 <212> ONI <213> AsT (400> 54 gagtgagtae aagcgaagca agctttcgct ttccatgtaa aagaacttgc acactaaagc tgagtcactt caccgataag tccccaaatc gacaqggcca tctcctcttc tcttgatcat tggagcactg ttcgccgcgg ctctcggcgc actgcagctt tggatgaccg accgagcatc taatctccct tgtcccataa atatcctgca tgagctccga tttttgaaca ct ctct cgaa taaaqttcgc ttatcttttt tat cctcgag tgaattccat ergillus niger attgatcta tatttcacat tggctgacac gttataacct agcaaggcga actttca cat tgataaggtg gaaccacttt tcaggctggg accgttggct ccccacaaaq ccttagcaaa caggagcagc atcacgaggt tgaacgctca ttctagctga aaggcgacaa aggacttcta tttgtcgag aggtctcgtc gcacatgacc at ggctgca c tgaacttact tact tcaccc a gct tct ccc cCCtgctgc gccttccgcg tggtatgcgg cggcgtcgcg ctgacaaaca tcatagctat caatcagaaa acgatcggat gtaaagtcat ac cgca att c itggcaagacz gacactgttc atttcgccac t tggct ggca ccgccagcaa gcttgtccct ctcactcagc acggctgtaa tttggcttct cccgaataca ttctgaccca acctcgtctc gctgcgcctc cgcagagcag taattaatac aagccgctgt tcctactaca gactacattg caaccaagat atcctttccg aacctttgac ccgcccctgg ttctggcgga ctgaagaggc agcctaccaa ttggtgattt caaagtatag Iaaacaatcga Iacatagtgct I atggtggcat atgtactatq atggcgcggt tgccgccgga actcaaggcc atcatgagaa ccgt acccgc cagggcaaac gtcgctgcaa ttgcacattc cgccaacgcg gcgatggctt tgtgttaacg tctctcaaat atcgatacta ctgcggtatc catctccaaa ccaatcttca catcattggt cgctqacgat gaatggctac z cgggctactg c ggaactgagg tggagcgact ctagtagctg tggtacggag tatgctcttt tattgactcc ttattgacag tccggactcc gagcttattt tcaccgcgcc catctactct ttcccgactc acgtcgtgga tggtgtctct ggggcgaaqa gaaagaagtt cgtttgctqg ccctttagat cgagacggaa cggtgattat tccaccccct tcgcctttcc attattgcac ]cgcaccaag 3actgttccg ~cgcccaagg a ;gcagccaag c atatacgtac ttggatctcc tcagtcactc tagatagaag acactcaaca tgattggatc gcatcgaact ggcgggggct aactcttgtc atagtcccgc tttgctcctc gcaagtagtc cgaggccata acgtcccgaa gaaggcggaa catggacatt ggatcctagt cttcccaagc cgaatgcacq cacggcgaga acaqccacaa 9cacccacat 3cttcgagcc ~ttcggccaa ;cactgtcag ~cgggcctgt ~catcgcgcg 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 88/282 gtacaagaag gagcagggcg ctaaaattga tgccatgatg gagtttgtag gttcccatca 00 tccaacggac gcttttattg gcgctcacaa tatgaacttg ttcttagcaa ttgcatccga tacacggcat taagttgacc gttctccgag gtagagtata gtgcttacaa atcagtctaa atttccactt acgttgtgct a ca tat cct c ttggaatcac cccgtaacgc actgggccct gcccgtaaga cgctggatcc aggcaacccg caaggatagg gcactcaacc ttggctatcq tacagqgatg tat at accat atcaatgcgc acacatacca cctttcaata ttttgacttt caccgagacc caacctcagt ccccagaata gactacatgt ctCgctgggg atggacgttq tgtccatctt catttgttgt tttccagctt tctattgagt ccttaaatca cctatctgcc ctccatttcc cgqttattaa atcgggtttg cgagaataca tccccagagg cata cact aa gctctttccc acgatgaaac cttgctaacg cgagcaggct catagcatat tcttgacaga agaagtacac tcactacgaa atagttcatg catct gcata ttgcaaccca tctccattcc catgtcaagt gctcaactac gggtgaaatg gggcgtcttc atttgccagc gggtgggata agagctggta gttattatgt tagtgcccat acccttacca Ctatcgtggg ggatatgacg agccgatgca ggcggaagtc gctgaatgat Cccgctgcct gacccctacg tctatcgaag acatggctcg atacatggcg tatagtcatt cagaatggta gaccaaaaca tacaatgttt ataaacatgc 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2590 <210> <211> 3290 <212> DNA <213> Aspergillus niger <400> gagaggcaqa aggagtcatt tai gcattcaaat gcaccgttta gc attgccatcc ccggtattaa ttl ctcctcgtta tcacgcgttc ctc gcgqcgccgg cactactaaa gac atcagcatct catccattta tct cgccccqacg ctctccgacg gtc ccctgccgga ctcctcatgc cgt gcctagcagg agcggagttc ctg gctcgtttcc tccgqcgctg qcc tcacttgt atagcatc :acttctc 3caggcgc :taaagtg :tctgacg ~cacaaca .gcctggt ctgcgct :gttctct attccaatgt ccacattcta cgccttatct acctccgatg tctagtctag atgtcatctg atcaattctg ttaatctatq cacgccatgg cgagccagtt attttccatt tttcattcca tgcaatcttg gcactgcagc cctccaatgt caggctccac cagtcacgct caatggagta tgccggcgca tgtctgttgt tat agat act atctcatgcc caatctcttt cggagtcccc gctcacctcc cccctccggc caagattcgt agqtagtatc gacataaatc ggttgtagga 120 180 240 300 360 420 480 540 600 89/282 tcctctgttc ccctcgacag ctcacaatgc gttccttctc cgttgtcgct gccgcgtcac tqgcgctctc tctctcggcc tgctggacca aatactgggg tat tgaaact gtggtcctct gat actot ca gagtgtcact ctggggcgac ggatcagtcc tagcagccgc aggtactgac cttggaccga tggaggctat ccaagccagt gatgtqtctc cagcaggagc gcgtgagtac ggaccgtacc tgtgatgctg qacacagggt aaaggccctq accatctctt caagctacgg cgagccccat tcctctgcaa taacacacga ttgtgccccg ttgggcgtct agcttcgagt tcacaacccg tqgacctggg tagccggtgg ttaaccctgg ctggtgtcta gctaccatgg tcttcgcctt attctggaca agcaatgcgc aacgtagccc gtctatcgcg ctatqacttt ggcaatactt tggtagccga tcaaagaatt ttcaaagtct tctggcaaga tcgaggtgag gtcgaagccg gccaactacg gtctcgttcc ctactggacc cttaccgac cgagcctttc acaattccac gct cgt cagc ctggcccagg aagtcggctg qagaagggaa tcaccggtgc caaggtccgc agaggtctct tgcgcaggag a aaa a aga ca atgaggtgct tgacctactt agaatgctgt tgggtcatgg Oct ggaacgt gtaggtgtag ctaccccatt gtatgtcgac gtttggtctg atagacqagc caacgacttt ttaccaccag gcgcggcagt caaactggtt tctcottat gacgaatgga acctccgtgg ttctggtggc taacaaagat gcctcct act ctgctcgccc cgactacggg cgttttccca gtctctgaca aatcatgagg gccgatggct atccagggtg ttcgctgatc caatgccgaa cgccgagacg atgttacctt tcggtggctc tctgggctta cctgctcttg cagcaaggta aaaattggga ggagctgttg ttttctgaca gtcacaggat att cotcttg gacccccggc caattcaacc octcccagac gcgtcgcctg gtaaccctgt aggagtgcgt ccagcggtgc ggcaacgcca CCgtcttgtg tgaggcttat qcggtactgg tttggtctta aacattgctg atgaggggta ccgtcattct gaccccaatc acacttcagt gtaaagctgc caccgctcta atacagcggt ccatgccacc ttatctatac tggcacagaa agaatggaac agcattacga qgaacaqtgt actcttcctt attgaagcaa ccqgagggcg atactcccta taacctagtg tttcgacagc cgaccgccaa accccttacc ccccgaggga atgcccgctc cccaagccta tttgagcagc tggagtactg tgaccggcca attaaaotag tctcaccaac cattgaacgt tagaccgcta atctcacact agttcgataa tgtt tctgat gCcttgacgg agtgcgcctg ttgcagctaa ctgcagcaag tgccaaggaa tgactttgcc cctgcccaac cttccagttc tatactaacg tcggacttga actgtatttc acagactgcg tataatgcct tgggaatggt tcattcatga acctccacta tacttccccg 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 aagttaacgg ctacacgtac ggcagcgcga agggtaaaaa ctccgctacg gtgaacagct 90/I282 ggacgggtgg atgggatatg acccgcaaca cgacgcggtt gatctggacg aacgggtagg 00 tctcccccta aggcaatatg ctggttagca ttgtatatqg aagcagatta ggagtgtaca attagatggt gagacgttgc ttgtctatgt ctggtattag ctaeggtactg gaagggtcgc tgacaaccat tcgatctggt atttccgttq acccctggcg cggcgaacga aggattacta aqgagtgggt taagatgaat cctttcgcat tatatatatt ggccttcact ccaaacccac ctggcgctga ttcacttgct cggcatqctq acactaatct aatgtgatgt cgactccggt acccgtgcag tgcgaatqag ggaggagtat ggtcataaaa ttcctaatta gactgtcggg aaagaccgtg ccacaaacct ttacagtggc accttgatac ggttatctac actacaatgc gaagataaac gtgtcgagca at tat tccgg ggtqtgagga tatgcttgat tgatgatggt ctgagcacgt ctattgttca act ctgccca aacaaagatc tcaattcgaa gaaagcagcc tatatctcct atgtqaagta tcaatgctaa ctttccggcc gcgqgttcca aggtggttga gaagatactg agatacgqct gctccatggt cggcgtagaa gtcttccccc atcgtgacat catttcaaca acgcccaaca gattctgtgg gggataggca taaattgaga Cggtggtccg ttgctcggac taatgaggtg gtggacatat atggctgttg atgggaagtg gctagacgct cttcgaggac tgaagtcact gcacataagg cttatagggq atcctgqaga 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3290 <210> 56 <211> 2044 <212> DNA <213> Aspergillus niger <400> 56 ggctttgttq ttggttcact actgcttccc tcagactact ct at cccct c gctcctccag tggcccgtca cggtgctctg cagcagtttc tgggagcgag cgatqccgag ggctgagcgc cagcctcgta ctttttttat taatacgttc ttttttatag tccctcattg aaccagcaca catgggcccg aacatcgatc attgcagagc ttcgtttcgc tact tctttc acatcagtat aaaactcaat tttgttttca tccgcctgtc ttgccgtttg aagcacgttc ctgctctccg tggcagactt ctgatcagac ctgttcttat tctctcttqg accaggctaa ccttctggaa aattgttttg gacatcatat cttcaqctac cttcaaggtt caaagcatac taaacccatt tggcgctgtc tggcggccag tctgttcgtt qtcaggactt aggattctat tttctgaaac ccagagtgag ggcgtcctct gaacqggtcc cggaagtacg acgacaaccc agtgctactt aagatcgtca gctccgccag tggcccccat ttctcaattc ttgccgggcc ccaccatgca ccttacccca gtcgtggaac gaataqctcc atqctqctgc ccgtcgagaa tgacatttga 120 180 240 300 360 420 480 540 600 660 cactggttct tctgacttgt aagtcttgga tgcagctgtt tactctttgg tacagtgatt 91/282 aacgtcgatc ggagtacaac ctcgtatggt cggcgccat t cgaggacacg accggaggcg gaccgcctcg caagtaccag ctccactccc ctcgatcgcg ctatgcgcaa caacaccact cggtaacctg gtt gotcccc ttggcggcat aggccttttt act agtttcc ctgtctccta gtctgtqagt gttattgcct gtatatactt aaccaacgta agat tacagttggg ccttcgaact gacgactcgt gtcaaggagc aactccaacg caagacacgt ctcaagqctg ggcaacattg a agt actccg qacaccgqta gttcccaact cttcccagct atcaatttct ttcttttgca tcaatccaac cgttgtcttc ttttcctgta cgtgggcaag caaggcagga tccacatcga cgagtccata qgtctcatct tgttcgatac cctcgacctt acgcctctgg aagccttcgg gcctggtcgg tcttcgccaa acggagtggg ccaacatcag tggcagacgg cctcccttat cggtctacgt tctcgcttgt ccaaggttgg tgattgaaca ggaaacacct gacatgcgcg cttttccccc atggatggat gtgcgtggct aaaacataga ttatggtggt tcatacgttg gaatctcaat caagaagatg ccccgtcgga tgtccccgac gttgggcttt tgtcgcacca cgagtacgag cgtggactca agagctgaag gctgctggat gagcagtgcc cctcggcgag caccaacacc tgattgactg cgctgcagat gcccctcgct gcgtgtaata agtttqctca gtatctacaa cactctttct gtatcaaggc tttaaaaggt gaaaccttga gacggataca acggataccg caggtatccc tcctccatca agtctggacq ttcggcacga tcgaacggat gacattggaa gaagacgtgg ggtggttaca tcgagcctgg accaccggac attgtgctgg tctgggcgat tggtgttgcc atatcgtctg cgtgcattgc ttcaagttac aaccctaatc gccatgttta gccgaagaat cqggacacac ccttcgatgt tcaacattgg agt cgtt cat acaccatcaa agcccgtcat tcgaca aaga actggcagtt gcttgaacac ttactgccta tctacccctg cca ogat ccc aggcctgtaa ttagtgtgct attttcctga tctcccaaga attttttgga tttaccttgg agtgccgacc catgatacaa tatctaatga atacgaagat 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2044 <210> 57 <211> 3916 <212> DNA <213> Aspergillus niger <400> 57 ttcgcagata ttcgagtoaa tacottgtat attaaoggaa cttcaaggat gaaattoaaa acgtaqagta tottgaoctc gaccgtacag ctagtgatct oacggtggta attgctcgat aagggtttgg gaagcgttgc aatgacctca tgatcccctt tcgattccaa actacagcaa 92/282 00 00 gaagcatgcc tgaccaacct gggtggtaac gtaccgaatc cacagcatta tagttgtgta cgactccagc aaggatcgat tagtcaagac agttattcaa agggtccgtt cgattccgat ccatct tact ttgccgagaa ccagtcgggc t atct tat cg atttattcct cattcaacgg atcattattc tctggtccca caattcacag tcaagagcag ggagctqgga atattttttc caccttggca gtcgtcaatc gqtcacgatg gagccggtat tcgtccaact cgacaggaaa ttgtctgttc cgaccgttgg cttgtatccg ctgtqtcccc tcacaacaac aatggcttgc ccaggagttt cgggaacagc tgtcatgctg cggtttggga tgactgcacg ttgcggagqc ga tgga at gg cqagcgtgac ctt at cat ct ccccaggttg gctccat ccc atatagtgcc gtcctcctgg tggcagaaac gtcaaggcgg gaaqacgagt atcatgtccc cgctcgacta agtccttccc ttcccaagtc atggctccct tgaaaggcgc gtcaagttac tagatgaggc aaatcccatg gatataggcg ctqgtcataa tgacacttgc tctgtttcgg gacggcttgg aagaaccgga agtgcgatgg aaggaagggc ggatttgcaa aggatggcac t-gagaattg gcctttcccg gaccggttcc ttgtttgctc cttctctccg ttgtttcgct gccaqgtcgg caaatgcagg agaatctgtt ataaccaccc tggaatacga catat act cc tgccgtgagc agctacacca ggttgctgta cgttgcattt aagagatcta tgcagtgacg gaactggcgg accgatagta gagtatttgt ggaacaggta acgaatatca gtttctaatc agattatctg ggacccaagc gccctgtgct actgact ccc tttgtgtcqg ccttgaaaat at ga qca gg tggcagaagc ttctccctgt gatccctcta caccatgcgc tgctttacaa tgataaaccc ggacagqgcc cactcgcgtc taattagctg acccttaccg ggtaatgtct atqqgtctca tccaacctcg atcagtcgqg gaacggggct taactccggc ggttcaaatt gtagctatag tacaataaga tcagatcctt tcgggctaqa cgatctggaa tttaactact tcacgagtga tgccgttgga agtgggacga aagggtggtg gaqqctgtag tcaggtgggt tccccttccc ctcgccttct tcccttattc attgactccg ttacccttgg ctaattagct cggcagcttt attggcagta acaacctttg acctcggtga tcgagtctcg ctcccccaac ggtgtgaggc gaaqctgtcc tcatctacaa gctacggctc ccaagaaaat cccqataact tcagacgtag agggaccgtc gcgctggcat ctgtgacctg gattattgtt ttgccaaaac tgctgatcaa atccacggaa agaaagaaac actcctggtg gggcactaac gtcacgggtc agctcctcgt ctccagcctc ttccttagat cggcgctaca tccaagactc ctccgttgct acaagattgc aaggtacgat ctccccaggt ttattatact ccttgtcctt gaggaataag ctcggactac gttcgggacc caacgagcgg 240 300 360 420 480 540 600 660 720 780 840 900 960 10210 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 aagtctcaat tagctggtaa agcgggagct gttgctgccg 93 /282 00 00 ggtgacctaa tcagacgagg atcgcctacg acggatggtg ggcccgggta ct cacccagt ggccttctcg cgcttgttca gccactaatq tacgaagatc gccttcattc actgtcgagg catcagatct gtaggaccgc atttacctta cggaacggtc acgcgttgca qcagagacca aacaagtaga gacatttatc tctcgcaaat cgttaactta tggggagccc cgcagaggca aatatgccgt gtatattgct tggtgggcct gcaaaatacc ttgcgaaaqt ttcttatttg gcggaactct atgctgcccc ttgatgcgat acccgaacaa tcaatgacga tCCqtgtcaa gatctgacta tggaCtacga ctgtgaa ccc atgggttcaa ggcatgqtat aagcggacat gCgatacggt atccagcatt gctcgttqcc cgatgaaccc attgtaagat agtcctttct ccgttactcg ggqgattgtc gaccacggct atatcatctg aaatccagaa ctttcagtct tggttcatgc ct ctgcct ct cggagcgtcg ctatggggtg gtctacaaag gcactttacg aggaaaccca agtcCtggag agtagagacc ttgtgtaatg cgggtccggt caactgcgtg ttacgtgtcc catgctcggc cgagggatct ctacacgtac cccgggtggt gt t tggt ggg ggccaatgtg agttactgtt cactccattg atcagccctg ccgtgtgcc cgaacctgag tcatgtagac tgttatgaat tcctctatca tagacttcgc tgqaacagct aagctaaaag gcgattcgtg ccgggtagag aggattgaca acctcgaaca tggtgatcca gcgtggagtg acccccgatc aagttgaata atccacacca ctgggtggcc aCtctgaccc cgatttgctt gttCtcacac tcgccgaact gaggagcttc attccgtttg ggcattgcca gttgctggcc aacttgactg at qccgat ca cgacttacgc ctgCttttga caaagcttgg tcccacttgg gaagacctgg tcatgtgctt tttccccct ggtaatacta gcatcggtgc caagcattat caaaaacagc atcgacattt ctagggccgc gggcgtgaaa gaccatcacg gagt cat ccc atgttgctac aaggcgagaa ccaatatcat acagtgacag ttttggagct ggtgggccgc cggaagagaa ttgcgtacca gtgatctgta acggacgcag cggqagcaga aatggtatga Cgtgggagtg ttcttttgct caagtccttt ggaaccgaag tagtggqca tctttccatc cagaacCgtt gtgggatatg cgcaccctca cagggaccca ttaatctatt tcagagatac ccaccgccct ccgggaccqc gctagaatcc cqgcaattcc Cggttccgga cctttgttga ctttggtatc qgtggacgct cgcgcagacc cgtggccgag tgccacattg cgaggaggaa ccgcaagatc agtttacaat caccgacttt cgactatgat gggtatcaag CCcgtgttac qaacaccaag aactgqgatg gacggattcc taccatggcc aatatctgta ttttgagttg gtactatgta gttaggtatt taccgatttC gagcgtcctq gtccatacga agtgagtgtc at ataacaqa cat gaaacgt cccagggtct tccgaaagcg acaattgccc aacaacacgg 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 94 /282 00 00 gcatgtttcc tttgccgtcc ggttcgttac ctataaagac agggtaggtc tgttcgggaa aaagacacaa tcagcgccta tcccgtccgt cgaagtctat tgccataccc tatcacggat catcagactc ataaca 3840 3900 3916 <210> <211> <212> <213> 58 1443 DNA Aspergillus niger <400> 58 atgcatctcc at ccca ta ca cgtcgtttcc gccagcgatg ttcaagattg ggtagcgaca atgttgctcg ccctgcacga gaagagtgga ctcacgattg aacttcgagt tacgacaacc gttggcttcg gacaaggaca tggcgcattc tcagccatca ctgcacagtc aca act acta tacgtgggag ggtgatgaca tacgatgagt tctacgagct acgacgagct attcccgctc cacaqcgtct ccatcaaact tgccagtacc agtccctgtc tggtagcgga tttcatacat acacaggcgg tgcacaatac gtgtgggcta caaatqtcac cgtacccaat caacattcat ccctttcacg agtacaccgg ccgtggacga tcgataccgg tcattcccgg agctacaagt caacttcagg tctggctcct tacggqtcgg ctggaacaag ctgctagctc ctcaqtattt cgttacagca cgatacgtcg aaaaccaagc actgaacatc aactccctct ctctgtcgtc ctctgatacc cttcggttcg tggaactggg tgtacgcatg ggacggcatt ggatgccgtt tagccccgcc cgatatcacc tgtctatgtt aacttcttat cgccaaatct ggcattct ct ttctggatgc gggtgacacg atttgcagag cagcacctcg tagtagttca Cttctctgct gcgtgtcttt gacgacatct gatgctctag aaaaggattc tqgtctaaca aacattgggt tgggttttcg gacgattctt tctgtcagcg actttcggac ctcggtctcg gcagaaagta aaggatggca tacaccgata ggcggcactt gctatgctgc tcggggagct ggtgtgaatt gtttcgaaca tttctcaaaa cgttcctcga ggatccacta tctgatgctg ctggcgattg gcgccagtqc cagcccgtga cagacgattc ccgttcgtcg ccgccgctct ctgatgagaa gttccaactg cgacccttga gcttgctagg ttgcttccaa gtcgaaccaa acgttttcaa cggtcagctt ccgtcggatc catgcgattt cttcaaqcga accacattat acaccatctc ttatcagcta atqtgtatgc acaccacctc caacgggcag aatcaggaag cttccttcat cacggctttc ttcattagct cacctcatct tgacaatgat cgatcaagat atctatgtac cacgtccaca aatgacatcg aaaagacaag cgcatcgqat cgatagttcc gtcgaatatc tggcact act ggacagctat ctccaacaaa ctcgaagacg tccgtgcaac gccgaaggac cgacttattt tqtgtttgac tgcgtcgaac ctcaacgact tagcatgacc gctttggctc 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 95/282 tag <210> <211> <212> <213> 1443 59 3300 DNA Aspergillus niger <400> 59 atgcttcgtg t tg cat t tta cagagaccat ttcaaaccgg agggtagtgg gagattctcg cggaactata aatgcctgga ttcgctcaaa gggtgctata tcggaqatgc ttgacttacc cgcgtcctca ttatgcctaa ttcgaagata gtagattcca gaagaagatg cctgttcaaa ctattqgata gaagatcatc gcgaaggtaq atgaggtata agctccgcct ggatcgacta gaagaacagt gtcttcgtga gattatcgct tgagcaaaat agtactcgcc tcattgacca atgattcagg gatataaggg cggccacaga tcttgcccgt ccgaagtgca agggtgtgca cgcatggtgt ccgcggaccg tcatcacagg ctattctaga agcaggcgcc aatctttcgg ccggggctgt acatcctggt ccagcattga agcaacggtt tcaaggagtg Cttcctttgc tgcttgatgt ggcgcagttt tgtcqtatta ttacaatttg caatcccctt gttcttgcta acggggtgtg gtcatctact tagcgagttt aaaaggaccc tqctcctcac cttccttgac ccacacggcc gtacctagag tcatattgat gaataactct aggttttcgc tat ccgagcg cgaaqtagat tgtcattccc gccattggag ggagatagaa caatgttgca tgagaaggag gatccgcttc tttcgaagtg cattgaccgg gqagtacgtg tqcgaccttg tatcaaaaca atcacaggat caaaagagcc gctcagtatg aaagtcacag acgttggagc aagctagcaa tacaccttgg cat gtt atag qgcgctggag gcagagttaa tacqagacag ttccatcgtg caccagaaca agtcctqatt aaqtccattg attagattcc ttgctqtatc cagctcgcca acattaacca ctcaaggacg caaagacgga atctcggatt caagagtacg tggatttctg ttggttctaa atttcaagct agtcggagag gttattttgt acttgtgctt cacgtgttta acacagcagg ctccaacact acgacgctgg tcgatctaac gcqgtatgat agatgtacca tqctggagac cacctttcaa tccagactgt tcggtccgga tggccggttc gtgctgtcta qtqtggagac ctatggagaa zctqgaagtt tcttttcgg acgtgctgga atcacatttc act ccagaaq aacaggcatg tctagccaca tatgggctcg ttcgaqcacc ctgggaaggg gacagatgaa agtcgtctac cgctcgtcga ggagcagctc gcccaagaac cttggacaag gaggccgtgg ggaatttccg ctgtaccgac atctgcttct ttatgctacc agagaaactc agatttagac ctctaccgaa aaagagagac gaagtggagt 120 180 240 300 360 420 480 5 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 atgccaacca tgtcactatc 96 /282 cttggtgttc cgtccgttaa qatqtctgac acattaaaga aggaggagga agctagagtc 00 gcagagcaaa aaagctaaag cctggaatag gatgccgggc cccttgttca tcggcacagg ttcaacctgc ttggaaaggg atgttgcgga caggaacttt ctgctctccg gtgatggtcc cgttatttga atggaagaaa gacctggaga gcaggtgccc aagttgggcg gctaccgcac attgcataca gcatatggca cgctccccca tctggtqcga agctttgcga gtgattcggc agcgttgatg acggccaata caggcatcgg ctgaaggtcg ggatctgaag agaagcgctt ctgaaaatga agtctatcca gcccatccca tccatttcga C cg tacc tg t ctgtcaaccg atactgttgg tctcattcca cctggaactc atgtgcccga actatgcagc aacggatcaa tcagagatgc aacttcaaaa ctct acagcc gtaagtcgta gtggtttgga tgaacgcggt cgaactttgc acgcccataa tgcccttcga atgaacagtc gcctgcctag acgtgaaagg tcgtggttac gattcacgcc gcgatgacga at ga agat ga gqgtgat gag caaggagatc tttcgtggac caaggcgcaa gcatatcccc gcagcttcgt gaacggggaa ctactccatg ggtggagctt gattttcgat ttccaagcgt agagtctatt gaagcaatta gcttttccgt ccctgtgtca tatcacgact tgtggttcct ttcttatgat tgagggtccc ct at aacatt agccttcgac tcccttgatq gacaattggt cgactacaag cgctctgaag ctgcgctaca tgcggtgcag ggacgaggag t cagtgatgaa c gggctgaaga cccaaggaga act actacag aaactggtgg agtagcttcg ccactgctgt accatcaact gaaqgagcta gagaagtatc gtcgagcgac agtggcgacg gttcgggctc gcagaagagc ttcgagaaca gcatggaaac agaagaccgt atgccgacga gatccaagac ctctgggttg gataccggat tccagcaagc ctggaqggtt agcgcagcct gagcgggtgcI gacatcattcI )tgcttgagg :cactcaaag z :ccqacgatg a ~acatggagg a agttggccga tgctggagag ccaggtctgg atgctgatgg tgcagctctc ctgtgtatac ttgagcaggt gaagcctagq acacggcgat tccgagcgat acatgctcgc ggagcacctt cgaagtctgt tgcgagtctt catttgctga tgctcagtga ttgattcatc ttcctgcctt cagttcgagg tcgtcaactt agattgttqa ccattagcaq caggcagttt :caagcaggt tgcctttgtt igactatcaa iattcgaaga1 ~cgacgatqa caagctggaa gttccaaatc tgcaqccctc ctctgatctg cctcctcatc tgaggcattc, ggttgtcgag aaactcggag cqcatggatc taccagtcga ggctgttcat ggtgaaggcg cgttgcgcgg agttatcqct gcgt ttg gg t ggcaqgccag gttcgcatat aatggttgca caagggtttg cgacgtttac ggatcacctc cat tgtggt a catccgacag gcgggctact taacccgtcc ggaaggtct c tgactatggg gtatgaaacc 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 'tgacgaaga tgatgagtga 97 /282 <210> <211> <212> <213> 2181 DNA Aspergillus niger <400> atgggagctc accccggagc gacaccggtc tggagcttga gaggagatca gcgcaggttc tacaaggcag ggcgacgtqc cagctcgccg tgggacactt accagcgacq ccagtcaagg tcgcctgacg aacacggctg aacggccctg ttctcccctg gaccgcaacg qactgggacc agccaagatc aagcccacga accctcctcg gacgagggcg cttagttcct tggatcacct cacggcggcc ttcgccgacc ttcagtggct agatgatcgg tattctcgac tcgacctcca tctggcttgg ccggtggcgt cctct ctct c atttcatcct agacctatcc acctgaccac acggcaatgt gtgccgaaag gcaaatgggt cctatgtcta atagtcctgc ataqcgacaa tgctatacgt gatcgcctag taggacgaac acttcaccga tcacgtccag tgatcaacac ccgactttga acccccaaga ccgaagacgc agggatacgt gtccatcacg tgccccacgg ctcccaatgg atcgggcaag ctctgacaat ggagctgtgq cgccggtttt tcgtggaaag cagtacagcc cgcctcccac t Caat at acc cccattccct taccttcaag tctcgtccca aaccccgqag aatagcgtac atactccatc ctccgtgaca cagacttttc cggcggctcc cgccttctgg actggcctca agagttctac cttcgactca ctgggcggat Cgtcgtccaq gctgctgcg agaaccgaag tcgtttgaca accaccactc tctacgctcc attqcggact ctcggcatca tcctatccca cgcatctacg gctgtattct tcttcagggg ccttttggag agcaaagcgc cacgacggct ggagttgaaq ttccaaatgg gccgatgaca tgggtcgatg gccatcccag gtgtcggctc acaagctgga gccaacgaga tttgacggca tccaagaaat. gaatggaacc ccaaacccca Icctccgcagt ttataccaaa ctcattctga tcaccgatga tctacatcaa cttctgactt aatcaaccgt acgqaacggc acagcatctt ccggtaccct gattgaccaa gcaacgacga cagagctgcc ctgcgactqc gagaatccaa ctactaatac ccatcactcc gagacaacct gcgatgcagg aatacgtcct gcgtctacac tcgaccccga actggactac accccctcgc tgaaatggca cagqaagcac gtcagccttg CCcctccggt gagcacctgg tagcgatatc cagcaccaac tgcaaatqct gacagattcc atacaatgat tgtgcggcac gcaaagctcg cctggttaac Ctatgacctc tcttgctaac Ctttgccgtc caatcccgtg atacgagtcg ccttgcaaag cgtcgtggca ggacgacttc atccaactct cqccagccct gcttagcggc cctccaagga cttcctcatc ctccaaggtc cgggttcggc 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 cagcagctca cagacgctat ccaacttaac tggaccggcg CCgcctacga cgacctaacc 98/I282 aaagcctggc gcgggtccca aagttcaagg gatgagttat ttccacaaca gtcatccaca acgctgcagg gtcaccgggc tattctgggg gtggtqqatt aatacgtgca gcttcggcgc cgctggttag gqtttgttga cggatccatc gtgacaagga agaggggcgt aagaaaacag tgggagggtc tgaatccttg cgatacctac gttcatgatc ccatgatggt gcatgagttc cggccccagc ttatcgcata gcccagtcgg cctcgtctgg gaatcctgat gacttcatcg acctggatcc ccgttcattg aacggcacct cgcgtcctcg cctgtggcaa tttttgaatt tatcagcagg gcgattgctt acacggacaa agggcgatga gcgatgcgtg tctggcaagc cat acagcac atgggattgg tcccqgatga tgctgggatg tggaggatac cggcgtcgcc ctttggacqc ggtcgagacg gcqcgacgca cccccagctc actgtttaat ggatcattgg gattaatcgg ggtgaatccg 1680 1740 1800 1860 1920 1980 2040 2100 2160 2181 <210> <211> <2 12> <213> 61 1695 DNA Aspergillus niger <400> 61 atgacgaggc tcacaagcaq qcattgatct acactgactc atatttaact qaatttcagg ggaaacacca caagctccta gcaaacatcg agctttgctg gtcaactact ccggatcgaa ggatacaacg tgcatggccg gaagccgcaa accggtggaa agacttct ct agctaggcaa gtggaacact tcgacatcgc ttggaggacc ctattcttgq tcccgttctc acgacggcag cacaggcatg caagggacat gggqattctc tggggaatgt cacaagcggt caccggacct tttacctgat tcgtaacttg cgttcccagg gatccaatgg agacgtgcca caagtggcca tggtgtcaat aggtcacaat ctgctacagc agcgtccagc ctatgctacg catgcaggtc atacggcact cgcgcttgac tgtggacgtc ctgccctatc gctggaaaac gagcgacgtc ctactaacgc aaaggatctt tacgactaca gcgaccaaga tcgttcgagg gatttgatag gatgacgcca acggctttgg aacaatcaaa gctgatqcgc a ca at cggt g ggagtggaca gacaaagttt gccaaggagt ctcaagtaca aagtcgacca tagcctcact gcaacttgac cggagt caaa aaccagtctc gccttgggct cttttaacaa cccgtgaact gagaaatctg ctggtagtct tcagtggaaa ctgttctcgc accccagaga tcgaaggatt acaccagcgc acccqattgc agctgcactt cacttatccg ttccagcaag gqagcccatc ttatggagag ccgaggcgtt cgt cgccct t ggcccagaac tat tggaact ggatagtttg agccatgttc ggct ctt tat ctgcacgggc cgccaacttg cattcccgaa 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 tttttgaggc catgtacctg 99 /282 ccaagctctt atccttggca acttcggctt accattaaaq gatggctcgg cgct act ccg tacgatccag gtcttgctcg gccaaggccg caggtggacg caacggagcg gataaqatgt ccggaacttc ggcccttgac actctgaagt ccgatgaggt aggtcctccc acggcgacat gtgactttga cgactcctct aqcagaacgg tccgggctta tgcctctgtt ttgagtcgag cgcgacgcag cctga ctctgagctt atacgacacc cggcacggcc gtacgtcaaa gagatgcgcg agtcaagaca tcccgcaqcg ata cggt cat cttcaccaat cacgaacttq ggatgatgcg gatgtgtatt ctttactacg atcaaatcct attacatgct gccaqacagg cagtggaatc gccaacccgg aagaacctga act accctgt ggcacattgc acctacaagg actatcctca tatttqtaca tgcaaacccg acggtcaatc ccgacaagca ctctgaccaa cgaagatgtt tgttgattct cagagacctt ctatgccatc ccgctgacgg atgtgtggcc aggctttgat ccaacagcgc caacacaacg ggcttctttg tcgatctgcc gatcggaagt cgccaaggag gagcaa ca ct tgagggaagt tctttgcact aacgatctgc gaagagtttc gt cggt ccgt ttcatggaga 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1695 <210> <211> <212> <213> 62 1581 DNA Aspergillus niger <400> 62 atgtactact tttgtggctc tacaaacagg tacgtcgatg gatcccaccg ggttcctcct ggctccgtct cagcccgtgc acagacaatg acggagagtt gcccatctcc tggtatgacc acatacgact ggccccggaa ctctctgqgt cgcccacgga tccccaccgq tcgctgagca aggctccctt ccatgatcgg acaacaaccc agaccgqctt gttttatggg atggcggcca agccgggagc cgattattca acctgccatt act gcct cga tqctgccttg gtggccgcgc tgcccgtctc ccgggcccag tct cat tccc catttqtgag tgagca cat c gaccgtctgg cttgttccaa Ctactcctgg ctcctacagc cgcatttcct ctacgggccc caagaagatc ataccaggcc caacaagtcc Ccagctctac accaagggat actgatccca ttcttctggt atcaatggag gagcacggcc aacaacgcca attccggttc cagtactcgc gtcttcaacg caactgggca tactacaact atcagctcgc gactgcgccg atctcgacat gtgtcaagag tcttcgaggc gcatgtctga catqcggcat gcaacatgct ccggctatgt gcgaaacctt agta cat cga gtgtgatgat ttacqgtata tgatgtacaa cccgaqgcat ccccgtccgc cttctccggt gcgcaaccaa ccccggtcct tgacgccaat ctacatcgac gqattcttcc ccacttcacc gqagcagaac cggcaatggc tccgggcaac caacctctat cgacgagatc 120 180 240 300 360 420 480 540 600 660 720 780 840 100/282 tgcagcactg ccgacgattt ttgcgccaac gaggtcgaaa acgtctacga catttactcc ggtcgggatg gttgactacc gagagcaaca aacaccatcc ggggatgccg gccgccaact ggccaggtgc gttcccttct gatgtqgcga agttactacc tacaacacaa qctttgcggt agtatgactt tgaacaaagc acgctgttgg aggatgtggg act ataactg tcagtagtgc gccaggcggg atcaaccctt cgggaaagat gggagggcaa ccacgaatgc ttcagatgta tcgtgaactc gtccgtgcag actcgccttt caagctgctc caactggctg gggttacacc gcaatttgcc gcttgcgctg tcccatctcg cagcacgatt t ccgaacccg 9 act ccggacc gccgccatcg tcgtccaccg aaacagggtg ggtggggaag aacattgtca tttgtgcgag gagatgtttg tcgagtttac cagtgggagg gtgagccgga cgttccctta gcgcatacat gtgacgacgg tcacggtggt ccgtgtcgtt cctcggatgg tgtatgagag agcgcgt cat agacggtggg tgttggattc ggctgaagcg cgagttctac caattacacg gcgactcatg cat gtacgcc gcaggtcaaq agtgacacac tggacatgag tggcggcaag cacgcccaag tctggcgacg qatgggacca 960 1020 1080 1140 1200 1260 1320 1380 1440 1 500 1560 1581 <210> <211> <212> <213> 63 3471 DNA Aspergillus niger <400> 63 atgtcttgcg tctgttgcga cctggttcta ttgtcgcctg agtcgacact cctggtcagg gctatacgta cgcagctcca gcattgacac gaagatgcga gctaccatag ttcgacacgg gggtacatat tctggctcca gggccgctgc atacttattc cgaggtcact tttctttgtg cgcccgtccg tccgtaccga tcaccacacc ccggggattc gtcgtctgct aggaggttqt agctgtccat tgacaaaccg catccacaaa ctctacctcc gcctctt tat agtttctcgc cccggccgct ctctctcagc ccagatggat cgccgaacqg gacgcctgcc gcctgtaggg gaaaagcgta gagtagtcag acacgtggtt aggagcctac gccgcgccqc cgccccat ca aatcctaaat gcaacgcccg tcgctcatta ttgaatggag cccgtaaagc aatgggactg cctgctcagg gtgtctatcc gctactgggt tgcccgggac tgtctgtcgc cgccgccgtc ccaatcccat ttcctgccta gtgtcaccac tacactctac acgcaggcgc accttcgccc tat acgatgt ccgactcacc acttctgtca ttgtgqtaga ctttctggqg tacgaacaat atcgccgccg cggatttact tcqgcgctct gagcatctgc gagaccccgt caagcgcaag cgaatcgagc ggaggatgat ggaatggcaa gacctgctcc tgcagagaat atactgcatc 120 180 240 300 360 420 480 540 600 660 720 780 101 /282 tttgataacc atgaggaatg cgacgttcgt cctgtgtatc gqgaccctgt tcacgacttt ggaattttga cagccggatg aaactgagta gatggctaca agttccggca cgtgcagacg qaatgcatcc aagccgttcg aaagcagcgc gcggacggaa caattcatcc gtccaaagag acgcccgacc tcgcggctgt aaactggaaa a atct gqatg tcgtatcggc cactggcacc tcggacctcg caactcgatg tcctgtacga t tggt cgt cg ct Ctgcga ca ctgcatccgc gttcagagtg ggattcaac gtttctattc actgtggaca gtggtgcagg aattcgaccc cagctaaagt ttctgtctqg gtgacttcaa gtcctgtagt gtgcagcgac gtCgcggaga acgagtgtcg ccacggaaac agctcgagqa ggttggatga gcggtcagaa ogttCgtgac atgccatcgc acacactgtc agttcgtgga atattcgcga CCaagatgcq cggaccctat gtgttagcca tqcccctgaa atgcagagaa tcaacgtcac tccaaaacta ccaaactcgc agaacttccg cagccaacgc ccggactcag cattgtggtt gaaggctatt gggatcagaa tgtcattagt tacgaattac taacattgat ggattacttc gcctgtcacg tcggttgggc cagcatgctg aggagacgtg catcctggat tgtggagatt ggtggctgga tactcgcggt aggatggatc ggtgatgcga tctccacacc actggctgtg cccagctctt gcctgctgcg gctqgacggc gggtttggtg ggtggccgac cagcatcatc caccgactac gattgtcgtg gtccgcaccg Cgggcagtgt gaactatctt cgatatatga attcgcgttg cggctggata atccaggccg ggccatgcga ctCCCtctgg cgtggaacga ttgacgcctg gtggccgaga ctcctgcaqg tcgagtgttg gagtgccagg qqcacgttcc gtctacgtct atcgactcgg acgattcccg cgaqgcacca Cgcaacgacg cctccggttc gccgacattg tacccccagg gttgtgtcgc tccatcatcg cagtacgacc atcaagcagg gccaagaccg cgctaccgcg tctaacggtg ggagaacgca aattgaggga tgggtaatga gaaacgcgcc ccgcagcagc ttgctctgca accgaccqct ttcagacgca agtqggaggc tcatcctgcc tcaacggggt ggcagacagt ttggcgacct ataacctqtc gcgaggctgc tggacaagcg atcqttcgcg gcatcgtcta acaccggtct cgaggaaagc tgcgcagctt ccaagaagac gagcgatcgt tgaacgctaa caagcctggt qacaggacac ccgtaaccga cgatcaacct tcctgattqg actgaaactg tgcaggaqaa cgaatacggc tagcggtgqa ggccggtqgt acgcqcactg gtggatcttg gaccgtgcgt tgaaggcccg gctt ctca CC gcgtctgctt gcatgccatc ttaccaqcag cggctccttc gcccactcgc cgtggtcatc tat cgat cga gtgggacttt cgatttcatt cgtacgagta tgggttcgga gccgtacgac agtagttttc gcaggcgccg gatctttgtg cat caccact ggacgccatc cgaggacgga 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 catctaattc gcataaggat 102 /282 gtgqaatacc atctaggatt tgcgactcca totcttottc ctgtcctqtc gaaggtgcag cagggagaga oaagctcgta tcgcggcatc goggoogaca cgogtctcgq aatggacaag cgtgoqgtcg atttctaagc caatacggct ctgqaccgct gcggtgacat cccatgtccg gacaaggata tgccggaatt tcatgggcgt agctctt cat cgttcgagga agtt gga tat aaatgcggat tqttctgtgg tacacagcga tggccccaac tctccgaaqa tcgacaatgt agtatatcaa aat ataaaqa qoggattctg gtcggaggaa qgtgogcaag gggtgatatc catgtaogag ccaggtgccg tqctgtgttg agtctacqtc caatttcato agtgagcaaa gccgtgggta agaccagtcc aacatggaga tggatcgaga gtcgattgcc atcctgacct aaggatacgc actgttccaa cagaaacoac agcgcaagaa accgccgtaa atccccgaca gtgaccgtga cagccttccg gctacgtggt aggtgacgca oaccgcctgg tggacggaca tggaagccot cagaggacot accatgcggt gtcgcggatc acggcgttoc acacatattt agaagaacga gttggcggac ogaacttgaa ccagatgagt agctaaccca gttcaactca gctgatcacc gat tgt toga agagactgac ocgt cagcag Occctcctac aaccccgaac oogoctacgg t cat tact to cgtgtctcao Cccggatgct 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3471 cggcattgca ccggatgctg atggacgaag ggtttgatgg agtcagtgat attgagoogg atttggagtg a <210> 64 <211> 1611 <212> DNA <213> Aspergillus niger <400> 64 atgagagtcc ttccagctgc tatgctggtt cagcaggtcc ttggaggtaa oggtgcoaag gcggatoaca gtgccgacgg gttctccaag tctctctctg acgaggctcg taagctttgg atggatcaga acctctctt ttccctcccc tgggaccaca tcgtcgatgg caagotggaa octggctctc ttggcatcga ccccggogtg gagaatgata agcatttgtt ctactggttc ccogttgttc tgtggctgaa cggtggccct gagcttggcc otagoagoat caacaagaag aactccaacg ogtccgtgat cttcottgac ggagcggcca cacggtgccg ccgctgcacg gatgaggtgg aagaagcaca gootatgatc aagcagtaca ttogagtctc gggtgctctt atccagccgg cagcctgtca cggcggocgt acoatgcqgc cattocagga ccagcttctt accgccgtoo tcagggtcaa oogqtt at ot goaatgaccc ccctcaocgg tctacaatga tOctccctto cgaggtcct ggaactgaag coggagagc cgactcgcac gaagacogat cgatgacaac ogagaatgat tctcttcatg ctacgcttgg 120 180 240 300 360 420 480 540 600 660 atgtoggtta ctcctacagt aaotctgctg toagoqacac gqtogotgct ggcaaggaog tctatgoott gottacoctc 1031/282 ttcttcaaac aattccccga gtatgctaag caggacttcc acattgccgq tgaatcttat gctggtca ct aacctgcagt taccgtccca cagtccatgg gagagcgctt taccagcgca ctttgctact gctgttggcg ctcttccacg atccctqtct gcctggactg gatctggtca ggcaacttca gagtcgagtc atatccccgt ccgttct cat tggcctgcgg acaacgctct gggtttgtgt ctgggcagaa cggct at ggg ctgaggtcaa gtgactggat tqatctatgc aagccctgga ttgtcgacaa ccttcatgcg tcgagttctt cttcgcttcg tggcaacggt tgacggcggt tcctcgctgc cccggcctcc cgtctatgat ctacgtcagc cggctacgac gaagccctac cggtgatgct gtggcccgga tgagcacacg tctctatggt caaccgctgg gagatcctgt ctcaccgacg tacccagctg cagtctatga atct actgta gtccgtggta gactacctga tcgtgcaact caccgcctcg gatttcattt caggctgaat ggcaagaaga ggtggccaca ttggqaggtg ctcacaagaa gatacaccca tcttggacga ttgagtcttg acaacgccct agtgcqagga acaagcccga ttgacatcaa ttccgggact gcaactggct atgcctccgc ttggccaggt tggtcccgat aatggttcta gcgcaacatc gtacqagtac gagctcctgc ctacagttcc ccttgcccct tagctctaac aqt cat cgag ccgcaacttc cctggagcag gggcaacaag tqagctggag taagtcccat ggaccagccc a 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1611 <210> <211> <2 12> <213> 840 DNA Aspergillus niger <400> atgaagttca cctgctcccc catcctctgg gccgacgaga caaccacctc acggcgcaag acatacagca tacaacgatg agcacagggg actattgaga acagctaccc caaattatct gcaccggttt cacctattcc ataccaccca cgcaaggcac gggggagcgg acgccattct cctggtatga acacgatcgt acatatcgac ttgccggcca cttgacgact ggaggacaga acttgacaca tgttacatac gtattctgcc aacgcaggct acagacagga gtggtaccca cg ccaa 899t ggggaagaag gaatgccgac gcaacgctcg ctccgtgccc tccaccaaag agcagtaact gtgtcggcaa gggtcggcct gtcgacttct gactatgcat gaagccatct gccacgcaga tggatcgtgg caagcagtgt ggtcattgca agaattccag ggqcgggcgc cctttcgtgt ggqtcggqat acgtgqaaaa atgacttcga cgccaagtca cqatcagagc aggatttcca cctagcggct gcgtcaatca act cctcgaa agtgcgcgag accagaaccc agatggcgac cggqcagacg cctagatgta aggtqtagcc cccagctgcg gtctggcgac 120 180 240 300 360 420 480 540 600 660 104/282 00 tcaatggtcg atctggctgg ctttggcgag atcagcttct ggggcgtgca agcacaagga ggagggtcta catggggtgt agatgatgcg actattgtcg aactgaagca ggqcaacgaa gtgttgacag acgtggaggt gcaaagtgat tcggccttta cggtgaaata tacgagctga 720 780 840 <210> <211> <212> t <213> 66 1722 DNA Aspergillus niger <400> 66 atgatatatg gctcctgatt gcagctcccc gcggacttcg ca tat gaaac atcttctctt tgggtcgcct aacttccacc gagcaagtcg acacaaacca gactgcttga aaggcaagcc cgctacaqtg ttctccgtag gaggccaqtc tacactaccg cttccggacg ctgccgqagg gtctcggtga ggaagccaga gtgggtggga tccgagcgct ttaggagata gcccaggcta tcaactatat atqtcgtggt cgccatttac agcagaaagt gcaacgatgt ggcttgagtc tcacagtccc acctggaaac atgctcatct gcctaccgag caggcgtgac ccgactcgag acctcgacga tatcgatcaa tcgacatcca ccggacgtgc aggatcttcc aatacacaga tcttcagcag ggacccgctt ctgagggcqt ttgctcgccc aatgggatgg gcaactatgt cctgggactt ctgtccctct tacacaccgc tgtagccaca agaccaactg tccgatgaag cat cgatatc catggccttt ggagcatgtt gttggcccaa aaacacaacc gcaaatgatc cct cat gcca gcccatttgc aaacgtcctc gtttctagcc cggaggccaa atacgccctc gccatccccg tgcagtgctt agccacgtgc cggagactcg tcagcctatc cgggccggaa gtcgtaccag attgtataat aatcagggac aacagcatcc ttctggttgt tcgacacccg atqcgcccat ccaccaaatg qcacaatcaa caaattagga cagccaacga gtgtcggtta cttcgccaqc ggaatttccg gtatactctc aacccacaaa tccatggcat tat ctcgaac agcacgtctt aatttatttg ggcgtcggag ttcccggcgt aaggctgtgg aatgcgagtg ccagacggac cat gggcaat ccgacggatg cgatgcatca gtcaccggga ccgatcaggt ccatcgaaga tgatqaagac ccctcaagta ctcgcttcgq acattgatga tctatggttt gctatctgga caaacagcgt actcacaaga ttgacgctaa agctccagta acqgcgagqa cccaattaqg gatcgtgtgt cgtgcccgtt acttttcgaq tggaagcata ggggtattcc ggctacaaac gacaaaaggc cgagtacaag ttatggacgg ctca aagatc tcgcggggat cgatttttac ctccgtt ccc ccgacctaag aataagcgaa acctagcacc ccagtacgcg agacgccgac gggaagcaca cgcgactttc tctggtgggt tgagcaaagt tgcacgcggg atct aacgac tgttacatcc tggagggttc ccttgcccgc tgatqtgtcq tgcgggaaca 120 180 240 300 360 420 480 540 600 660 720 '780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 105 /282 agtgctgccg cccctgtctt tgcagcagtc atctctcgac tgaacgctgc acgtctcgag cagggtaaac ctacactaqg gtttctgaat ccttggctgt actcactcga ccagcaagga tttacqgata ttqtaqacgg cggatcagtg ggttgtgacg ggtcaaatgg aggagctctt gtcccgtatg ccagttggaa tgccaccaag ggatgggatc cqgttactgq gctgqggaca cctctgtatc agactctgga gcagttqgcg cagtctgctt ag 1500 1560 1620 1680 1722 <210> <211> <212> <213> 67 1758 DNA Aspergillus niger <400> 67 atqcgttctt attgtccatg tccgaccacc tccaagctga gaggatgtcg agcgccaaca gataaggtga agattgcgca tccccaacga aagattgaca ctgtcctgcc agcaagctgg ttcgagaagc gtcaatgatc ctcgtcggag gccgacaacg tcggctctgc tactacgcca ctcgagtcgt cgaacccaat ccgqtctcta aaaagctcgc agataaactt aagacttgtc acacgctgtt tcacccatat acaagcttct caacagagta ccttcttcgg cccatgtggc tgaaggagat gcttcggcag tgtttaacct agaatcaatc ttgctcatcc agaacgagcc cccaagtgat agcgagtctg ccggtgacga tcaaccccat cacagcactc cgcqgtcccc gtcgatcgcg aacacctggc cccggtqgcc ttcccgccag caacgccacc ctccatcccg caaggaaaag caaacgctcc gtacaatttt cttcctgaac gccctcccag gacgqcttcc cctcccggtg ttacctccag ttccaactcc caacctgatc aqgtatcgga cttcccggcc ctgtgctccc tccggctggc ct ggeacgca qaatcgcaat agcgacaagg ggcagcttgg tttgcctact gatgatctgg accactgctg aacagctcgt gqcaactaca gaatccgcct agcttttccg ttgaccgagg actgagttca tactatgagt tatggtgacg ggacttgttg tctggctgcc acctgtccct tggccgcctc atcatgtcga agaacctcga acggccagtq ctgtgattaa tgaactttgc accaaagcgg tcgactcaat gtctgaacca cctgtgccga ctcccagcgc cgtattctga tggagttggt cggacctcga tcacttctgg accttct ct c acgaacagac gcctgcgcgg gaaccaccga acqtgactgc gaccaacgcg agatgctggc tcagcttgaa gctggaccag ctggctgcgc gaccacggtc ctcttcccag cgacctcatc gcgggcqcaa tgt cat cacg ctcqtcgggc ccttgccaag caacggcggt tgtggaattg cgaacctgcc caagcccaac cgttccagag cat cagtgt c cggcaccaac cgtgggagga 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 acaatgtcct atgcccccga aatcgcctgg gaagccagtt ccqgcggatt cagcaactac 106/282 ttcqagcggg aacgagacca gttgctgccc tccggcggta gctcgtctgc gggtacaqaq ccgcagaatg acggtcggat ttggtgctgt cgtggttcca agcagtacta atagctttga cctcagccgc gggcgggcaa cgttgactga atgagactgt gggatccggt cgttgtag gaaggaagct ctcgcaattc gcctt cat at gtgtcccctt gtccacgctg tgtgacgggg tgccggcgcg gactggattg gtgcagaact gccaacttta gaggtt at ct ttctctqcgc ggtttcttga ggccagtcga ggcattatcc ggacttcctg acctggcgca gcggtcgcgg tctacggcgc tagtgggcat accccctgct tcggatgcaa cgtgggcgca actttgagaa ccacatcacc atttcctgac ccgctacggc gctgaacgat ctatagcaag tggcattgat ctggaatgcc gttgaggcag 1320 1380 1440 1500 1560 1620 1680 1740 1758 <210> 68 <211> 798 <212> DNA <213> Asp <400> 68 atgaagacta ctgacggcca cccttcaagc agctccaact ttcgtcgtqc tccgcctggg gacttttgtg tacqcctacg qatgccagca gtcacccaca atcgtcgagg actttcacca atcatcgaca gttgtcaagt erail1us niger ctgctctctt agcgccaggc ctggcaccaa gggccggtgc ccaccccctc tgggcattqa tccagggcag acttcagcgg gcgacaccac gcttcacggg acttcgagga gctgctccgc tcgagcagaa acgtctaa gaccgccggc tgctcgggcc cgaggtcctc cgtcctcatt cgtgccctcc cggtqacacc cgaggtgagc catctccatc cggtactgcc cggtgttgat ggatgactcc taccaaggat tgaggtgctg ctgctggcca aagcgctcca gcccttaacg ggcactggtt qgtggctcga tgtgacactg ttcgatgcct tcggccggtg acgattgaga ggtgatctgt ctcgttccct ggttcctctg acctccgttt ccactgctat cgaaccgcca gcaccaagaa acactgccgt gccgcgagga ctatcctcca ggtacgagtg ataccatcaa acgtgagcac gtgagtacaa ttgccgactt ttggccctga ccgtctccag ggccgctcct gagcaaccct tgtggagtac gaccgccgag gtactgtgcc gaccggtgtg gtaccccgac ggtcaccgtc tggtaccacg cgctgagtqq tggcaccgtg qgatgctacc tagcgaggtc 120 180 240 300 360 420 480 540 600 660 720 780 798 <211> <212> <213> <400> 69 1743 DNA Aspergillus niger 69 107 /282 atggtcgcct gtcgtcctgq accagctcca gagaagctcc gacgacatca aaggcaggcg ggcacagcca aagctgcqca tcgccgactg cagactacca gattgcctca gttggtttg cagtactttg aaccaggaga tcgcatccct gtcgagacta aagaccaacg gttcccattg atct ccatcc ggcaccgaca gtcggcggca aactacttct atctctgcct cctgacgtgt ggccttgtgg aacgatgccc tcgagcggct gatgtggagg ccggcgacag taa tttcccgcat agaccgtcaa caatttcttt tggccgtgtc atgagcagtt tcacccagat accagcttct caacgcaata ttttctttg aggagaccag aagagcagta gcagtttctt acattcccca atgatccgga tgccggtgac ctaccgacga acgagctgcc cctacgccac tcgaqtcttc agaccgaatt cccaagacgt cgcagccgtc cgacgaagaa ctgcgtttgc cgggtacttc gtctgcgggc acaagagcct gcgctggagt ggctgggaac ctcggcaggc gtctgttccc gtccgttgct cacccctggc tcctctcgca ccataaggag caacaccacc ctctgttccg aaagtccaac cagaaagaag tagcattgac gaacgagtcg gcagagtttc tggtgaagcc ggagtacatt gaacgagcct a ctggt tat c ccgcgtatgc cggcgactct cacccccatg gcccgaaqtc gtaccagtcg gtactacgag aggttctcct tggcgctagc caacaagaca gaatgacatt cattccttgg gcctaatttt ttcgcccttg agcgactgga ct ggcgcgt c aaggacacct gatgacgctg ggtggtctgc ttctcggtgt gatgagctga gctgcgcgct agcagtaatg tatacgcccg gccttatact actgttgaga gatctcgatg accggaggat tacctgcagt agcaactcgt aacctcatcg ggtgtgggcg ttcccaggaa gcctgggtgg gatcaggtgg cagtacacca tactacgaaa cctgtgtttq tccttgggct accagtggcg gcgagctgga gccaagctga ccgcccCtgc agctcgtgga agaacctgga acggccagtt ctgttgtggc tgaactttgc acaagagcgg ccgggtccat cggcggccgt tgtgcgagta aqgcatcgtc cggatttgga ctatcaacgg tccagaacat ctcctccatt actacgagta acggcgatga gcctgatggg qcgcatgcat catgcccgta acagctccgg agacctacct acttcagcgg cttatattga cggggatcgt tcctgaaccc aggcagtggg atgccacgac aggaggcggt cctggccagc ggctgctgat ccagttggag cttggatctg ttggctgaag gaccactgtg atct acccag tgatctcatc gcgtgcttcg cat cact ccg qggaagtcgt tctqttcacc gggaatcaac cgtgggcatc cattCCcgac tctgctggcc cgaagatacc cacacgtggt gtccaacgac catcaccgcg cggcttcagc ggacaagtac tcgcqcgttc tggtcagctc cgcgctgctg ttggctgtac ctgccaaggc gggatgggat tcttgcgttg 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1743 108 /282 <210> <211> <212> <213> 1896 DNA Aspergillus niger <400> at gcatgqt c ccggcggctt c~1tctaactccg ~-Igctgaagaac 00 Sagctttcgtc cgccaaacgc gatggactgg ct qgacaat a cagcttccac atattcagag aagccagaag ct act gaca t gacgcqacat attgtcaccg gacaactaca ggctcct at c tCcccaaaca acagcaaacg ttccaatgga caagacggct cgtatgcgca ggcattgtaa aacqccgqat atggcgacqg gcatgggcag gagaaccctt gtctgggcaa tgcgcctagt cattgcatac aatacgtcaa attataccga tcatcgatga tccatggtat tcttgtcttt ccaacgtttt tgactattga aggcagtggg ggactctggc acattgatgc atcaagttta acccctggga ccacaaccag tctacaacct tgtccccacc cctaccacga ataacagcgc ccgggttcag tgtacatctg ttcacgaata gcctcagcgc ccatccgaat ataatgataa t gaact ata C ccatgctata atgcagcata aacttcagca ttctgtccat tacagcagct ccactttgtc tgacattgac cggacattcg gagtccggag caatgtttct agcggtatct gctcacctgg agagactacc tccctggggc cctatccgca aggcaacaat acgtccatcc ccgatcatac cctcctctat ccacggcggc caacgcaaac gatcgagtct cactcacggt cctcgaatcg caagcccaac atgtggtgtc gagcgtqaat cgaggtcttg gggacattgc gccgtggact gtagacacga cgactggttc ggcgacaatg aatgcggatt ttcttcacaq gctgcactta act gaagctg gaccccaaag aggatagaaa actgtccacg acaaacgatc tccgcataca gccatcgcac gaccccaact atcaacgcct acactcggct cgagacaaag tttgcaaccc actccgtcgc qtatccaatc ggtggcatgg gatacacgca cgggactatc accatgaacg tggaacctca ctttggt tat tggactccct atcgatcagt agaacattgt gagttgcaca tcaatgttaa gCgcgttqcc gaggagcaag cagaggggcg ctaagctagt cagacatgta gcgtggttga cagcagaagg cctggataag actggaatcc tgaatttcca ccatcgtcca tcaccgaatc actacgtgat cacccgatgg gtgatggaag gtctcaccgg gcgaaqgctg caacgtctta cttattctac gcqtgcacgc tcqacaagta cctggcatat tcgtctgacc cgcagtgtcc tcctggagcg tgtatacttc tattggaaaa gagcagccat ggacgctata gaacgagtac ctaccttgtc tgagcactgg ctatgtcgca acatcgcacc cgatggacgg gaccggcggt atggccatac actcttctac cgctggcaac cctcaacgca tatccccggc ttttgacgcg cggctcccac gggcgacttt cactatgggt ctcctt tact cat cggaact cgggaagaat 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 109/282 00 00 gatgggtcqa aagttggtgg gacgcgatcc agggggtttg cggaggggqa <210> 71 <211> 118 <212> DNA <213> Asp <400> 71 atggtcgtct gcgccggctc a cccgcacca gtgccccaga aatgacgagg gacaccggat ggtcacgatc atctcctacg ggcggtgtca gtt cagaaca cagcccaagg ttcgccgtgc tccaagtaca ttcagcaccg attgctgaca gagcaggttt accaaccccc tacatcaact aacagcggtc ttcaactctg <210> 72 ggccggtgtt tggatgggat ttgacgcaga cgaagagagg gtacacttct tagaaacggg gtgcctacag atggaaagta cttgatgatg ggcactgcaa ccatgtaatc cqaacttcgt gcaagccagg cattgtgttg actggcggga aqaatcgctg tgagatctgg attgqggcaa ggagcggctc atagtagttt aaattggatg tcctacggga tgttag 1680 1740 1800 1860 1896 ergillus niger tcagcaaaac ctactcgcaa t caacct gc gcgtgaagga agtacctgac ctgcagatct tgtacacgcc gtgacggcag ccaccaacaa cggccaatga cgcagaccac agctgaagca ccggttctat acggctacag ccggtaccac ctggcgctca ctgacttcac acgctcccat tgggactgtc agggccctaa cgctgccctc gggctt ca cc aggcatgtac ggctgccagc tcccgtcact ctgggtcttc tagctccagc ctcggccagc qcaggctgtt cggccttttg cttcttcgac cgacgccccc cacctacacg tatcggtgac cctcatcctc ggagagcgag tgtcgtgatt ctcgactggc cat cct gggt gctgggattc gttctgggtc atcaaccaga gcccgttccc aagggtagtg gtcggaaagt tcggacgagc gcgaccaagc ggagacgtgt gaagcagcca ggactgqcct accgtcaagt ggtgtttacg gatgccgata ggcagctcca ctcgatgacg gaagccggtg ggcgactaca agctccacct gatgttttct gccgctcagg tgtcctccgc ttgcccggcc tggccaaqtt ccgtgaccac ccaccctcca tcccttcctc tgagcggcta accgggatac gcaagatcag ttagctccat cccagctgga actttggcta gctcccaggg gctccagcgg aaatcgtctc gctacgtttt aggccgttgt gctttggcgg tgaagagcca ct tag cgtctctgcg tgccaacaag tggcggtacg gccccagaac tctggacttt ggagcagacc cacttgggac tgtcactgtc ctccgagttc caacactgtc ctctcccctt cat cgatgac ttactggggc cttcagcgcc cgcctactac ctcttgctcg tccgggcaag tatccagagc gtacgtggtc 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1185 110/282 <211> <212> <213> 1197 DNA Aspergillus niger <400> 72 atgaagtcag cacaagctca gcccatgtcc ctggtcgagg ctgaacgcac gtcctggaca tgctacctcc gaattcgcca aagattggcg cttgcctttg gtqaacaaga gtctttgcct ggtggtgtcg gcttactgqg aacaccggtg gagatga~ca tgcgacaagc atct cctcgt at ggactt cc tggtacagcg cctccttgct agcttaacaa gcgctctggg agaaccctat agtacttctc ctggcagctc acaacaagta tcaagtacgg acctgaaggt ccttcggccg ttqttcctcc tctaccttgg acaaggacca aggttgagct tcattctgga atgctcagat gctcqtccct atgactacac ctgagccggt tgtatgacct cacaqcatcc ggtgcctctg ccagaagtac caatgacatg tgagatcgag gaacctttqg tgattcgtct ctctggcagc caagggacag gttcgatggc cttctacaac agataccaac ctacaccggc tgacgccatt cactggtacc cggtgctaag gcccgatgtt cttggaggtg tggtcccttg gggcaacagc gtgctgttgg gaagaqcagc atgggtatcc agccgtcatg ctgggtactc gttccttcga gcctccagta cttagcggat gacttcgctg attctcggct atgcttgacc aaggagqgtg gagctgatca gctcttqgcg tccctgattg aagggctgga actttcaccc cagggctctt gccattttgg gctgttggtc gctgtgcctc tttacacgca gcccgtccat atgttctggt ccccccagaa gcgaatgcag cgtatcacaa tcatttctca agqcqaccaa tgggttatga agggactcct acgagtccgt agattcccct atgatgttgc ctctgcctgc ccggccagta ttgccggcca gcgtcagtgc gcgatgcgtt tggccaaggc cgccgaggtt taacatcgac ccacaaagag ggacaacttc gttcaaggtt ctctatcgcc gaatggcagt ggacaccctg tgagcctggc caccatct cc cgacgagccg ggcgaccttc ccgtcgcaag tgagatggag tgacctggct caccgttgac caacttcacc cttcatgggc cctgcgcaag caagtaa 120 180 240 300 360 420 480 540 600 660 '72 0 780 840 900 960 1020 1080 1140 1197 <210> 73 <211> 1182 <212> DNA <213> Asperqillus niger <400> 73 atgcgcaagt accgcttcca tcccaccaag cctggtccct caacagaccg gtcgtccgta cactgaaaag cccatcgggg ctggtgcgga agaagagcac caccagcgat gaggttggcg cagaacqact ccatgtatct ggcgaccgtg gggatcggaa acactctcag cagctccatc gtcgggccca tatccggcag aggttccggc cgaagatgtg ccccggcgca qaacctgaag 120 180 240 111 /282 ttggactttg cttctatccg accttggaag gtgggcaccg gcagagaaga ttcagcaaca ctgcaggatg gacactgatg gcaggtgaag tcgacctccq gataccggta attgacggcg caggataagc gaggacctgg acactggttc agaacaagac gtgaatcctg acgacgtcaa tgtccagcac tcaacacggt acattcccaa acgagtcgtt aggtctacta cgacqqtaaa cgacgctggc cctattatga tacccactgt cqttttcgga agctgatctt ccatgcgatc gcaaatctcc cat tggcggc attcgcccaa acagccaaag gtcggctgag ttacaccttt cacccctgtc tggaaagacc cttggtggac tcaggaagta gtcqtttgcc ggcgaagacg cttgggagac tgggtctggt ttcgactcgt tacggagatg gtagtcgtca ggcqaagggg tccgtgaaaa ctgttcacgg ggcttcattg gataacagtc attaaccggt gatgacacgt cagggctgga gtgggtgaaa ggctatgtct acatttttga ccaacaaact ccaaatcgag gatcctccgc agaaccaagc acgqattgct cgcccgtcga ccaagctgga accaggatct aaggcttctq cgggtaacac gtgaggccat tctatccgac agcagttcgt atggaggaat agagtattta cccctcaacc caccttcaag atcagggagt cgttgagctg cggtctaqca gaacatgatc tacctggcgg ggtqaagacg gctattcaac cgccattgct ttatagtgca cgatacggeg ggtqcagaag ccaaagtcgt tgctgtaagt 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1182 ggtgatatga ccatggacat gcattgctgt tggcgttaag gggtgatatc gaagctcact aa <210> <211> <212> <213> 74 849 DNA Aspergillus niger <400> 74 atgaagttct ctcactgaga cctccctaca gattacagct ggcgagttca ggctacggct ggtatcgacg gaggatggcc ttcaacgaca aagagcagcg ctaccatcct agcgccgtgc tccctggttc ccaactgggc ctqtccccag actacaagaa gtgacacctg agacttccta tcaccatctc gtagcgccac taccggctcc tcgcaaggag cgacaaggag tggtgccgtc tgtctctqct caagagacaa cgagaccgct cgatgcctgg cgagggtgac cgttqagaac ctcttcgcca gcccgcgccg atcctcaagc ctgatcggcg ggatctagca tccgaggagt attctccaga tacgagtggt accatcaagg ctqaccactg ctgccgctct ctggcaagcg tqaacggcac acggctacac gctccagtqg actgcgcctc ctqgtgtcga accccgacta tcactgtcga gccagtccgt ccgagtggat ggctgctcct ccacagcaac ctccaacgag caaggtcact ctacggcggt cgcttgggtt cttctgctac cgcctacgac ggccaccagc cacccacacc cgtcgaggac 120 180 240 300 360 420 480 540 600 660 ttcagcggca acgtcgaggq tgacctttqc gagaccaacg 112/282 ttcgagtctg gtgactctct tgtggctttc gctgacttcg gctccgttac cttcaccaat gctgaggcta ccagcgacgg ttccactgtc ggcccctctg acgctaccgt tatggacatt gagcaggatg gcaccgtcct caccgagacc tccgtctctg gcgacagcgt cactgtcacc tacgtttaa 720 780 840 849 <210> <211> <212> <213> 822 DNA Aspergillus niger <400> atgggagatt gtctctgaaa tctaatctag t cacctgcat ccttcaccca gactatgcca gcaatgagga gacatcaaag ccactggtgc ccccgtccac gatgcgcgga ttggcactgg tcatgcttgg cttgtgacta acggccccgg cagatcagga tgaacgcctc cttcagacgg tacccgttgc agacgcacgg actactattc gcagatccgg ttagggctgg cggacgaaga tctccactga cataccaqgc atgaggatat gctggagtga agtgtcgtca tgagatctca atatctgata ctctgatgct atattcatcg aggccgacgc cgtggagacg gtacgaggat cccttcagag tttcctagca tgccggacgt gggtgagqat agagacgggc gcagcagcac ctcacggcac gtacttgtaa gcctcgt ccc gttccccgtc gtgcggacga ccagacatcg caggctcacc ggcqagaagc ggacacgcct gcatggaaga tatctctgcg cgcaatqtca aaggaggttg agcgttccct agctacctgg cgggctttgg taccaccctc gagtttcgat ccctccccgt tcatacacat gtgatgggta tgtggaggga cggagaagaa cattttgccc agttcatcct ccttcttcca ccgtcgcgct ag aaatccgcct gccattcaag tttcacattc aaatgtccat cattctcgat tqgcatagca tctgatgtcc gctcgacttg acatctcaqc tccagaaacc gtacaccagc tgttcccgcg aatcaaggct 120 180 240 300 360 420 480 540 600 660 720 780 822 <210> 76 <211> 1629 <212> DNA <213> Aspergillus niger <400> 76 atgggctcaa ggcagggaaa ggcccccttt ggctggggta ggtatcaacc cagaccttgg gttgcacaac cagcagaacc tcagcgatgg ccactgcgtt ggagacggaa tatgccacca gcatcggctg gcacttatca aaatcggttc tgggtcagcg aacccgatat ttgtgtacga taccggggag tcggatggcg ctcagtcact tgctcacttt tcaactccct catttcacat tccctattga ccataacaac atgaattcta tcagcctggc gatcgatagc ccagtcctac 120 180 240 300 113/ 282 00 00 ctaacctcca gcctggqagc cccgaggcat agtaacttta atcatqgtgg gagacqatat gcgtattacg gatatccacg tcqgtcaaac gcagcgctaa ggtctaggcg ccggatggcc ccaacctttc tctcagccaa acttggcaat ctggcctcgc gatgcagtgg tttgggggat tggcgatcat agcgcqatcc cagaactcgg ggcatcttca tccaqgtga ctctctcctt acagatacta ggcaatacct gccgcgagaa gcggctcgta tcgcagcctt accaagtcta ctqctctgga aacttttctt ctgccatct a cattctgcga ttgcccctac tcgagctggt ttgactgtga actgcagcga gatatcagtc acaagggact gqacgatccg tgtccattct caqcctgtgg aacattgctt catccgcctt cttcagagaa tggaaactcg caccaccaag gtatcctgac cgcagggatt ttcctcatcq tcgtggcatg atatattgac cggatctggc cggctacttc qtatctcgaa gtatggcggc caatctgaat cttttccaag atgqgggttc ggtggaatac gctgcctccg cccqtccaat gtcgacagaa ggtgcaqacc tgactttcaa gttgcaatgg ttcctgatcg accccggctc caggcgctcg atggacctga cgtgctgcat tctccggtgg gttgccagcg gatcaacttt gccgagacca caaagttatg attgatccca cagtatgtcg atggggacca ccatacggcg ttccaggcga cagcaagaag tcgccqcggg gtttacttca qatttcgcac aatqaggaca gcgacgccga ctcgaatgtt aattcaacgc ccgtatccta cggaccttcc cgccgcaggg taactcgcaa aagcacaggt gatggaccaa cggatgaaga actccaacgg gtatggcggg agacgaacgg ccqaacgatg actgcgqgcc atccctcggc acaacgatgg tat gtaaccg cgqa tga tgt gcggaggaga ctcaagggqt ccgtctttgg ccgtggggaa ttggacagaa catgggaatc tgaaactcca gtactttgct cacgccgtgg ggagtaccca caatatgagc ctgctcggca tacagctacc tgatttcact agqtattgga gactacagga ggccgcatgg tcagqacqcg catcacttqg gccqcactcg gcagttcccc caaccaagag attcgatccg ggagtttacg atacgtcatg gttatcacgc ctcaagccaa 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1629 <210> 77 <211> 1176 <212> DNA <213> Aspergillus niger <400> 77 atgaagctct caatagctct tgcactcggc gcaacggctt gttgtaccgc agcaagaacc gctgataacc ccccaagatc gagaagttct tgatcgagtt ggctccttat cagacgagat cgacgggggt gttggctgct ccccaactca tcatcatcag gggttaccga gqaagaaaag 114 /282 tgggacttaa aactggatgg cqtgaacttc atcgatatta ctgaagaacg aaacactggg ttctacccaa gagaaggtgg aaatttacct tggctataca actgtggagc cagactaaca tccatcctag gctttgcgtg gaattccact caatataaga acccagggag gatgagggac atcoaaacca cccqcagcta gatgacagca cgttgcatgc ttccccttct catttcacac gt agggt tt c agttcqctca aaactgttgt ctgcacctgg gtctgctgca ggtactcqgc gagataagcg ctctggacgc tgacacaatt gatgtggcta tggcgacgga tccggtatct tgqtagctat gcggggtct c tcgctactat ggatgtcatt ct cat ggggc cctgggcgca tgccgatgat gtcaqacgcc agaggaaggt agacatcaag cggtcgtcaa cctcaaagat cqcctattcg atccgaaatg aagcttcgat gttcactatc tccaaggaca aggtcgtcca qagcagtcgg caattcagta cat caggaca gacggaagtg attgtccggg ggtatgcttg gcgatgcttc gaagccattq gtcactactg ga ccacacgt gaaaacagca ca tat gctqg cqccgacgat acatggagca ctggtattga gtgcagcaga tcattgctcg gcatcaatct gaaccgtgac gcaacgcttc gttcgcaagc aacaqgatat ggattatggt agtattgtgq ccgcaagcaa acaaqaggat agcatgcgag qaagcatgcg aaacctcaac qtccqcaaag gtacggcgcc gatcccaggc tttcctcccc tatactcgaa caacacaatc catattctct gactggttat tgactacgtt tat tggctac atatqgctat ccacacgact gttgacactt 240 300 360 420 480 540 600 660 720 780 840 900 960

102- 1080 1140 1176 ggcttcgctt acgagctggc ctttgctcaa ttctag <210> 78 <211> 1329 <212> DNA <213> Aspergillus niger <400> 78 atgagaacta ctacgtcttt tgctaggctt tttgctagtc caacaaaaaa taacgatggg ggcatgatat ccgccccttt gcaccaaatg gccaactata gcaagttctc gtacgacaaa ctggtggctc tcgacggtgt catcgtcagc gCcgatgtca acggcaccaa tttacctcga gtctacgata tggcaagcct cacgaagctg gacgctggtc gaattgcgct taatgtaact aatgggaaqg agaatattac tatcttggag gatccatcgc caccactttt ctctgcttat gcattggcag aaactggtat gtccaaaatg gtccatccca gaatttgcct tacctgcagg ttcaccacgg gttgcaactt ctgttcacgc tatacgacgt tggcctcagt atggctcacc ttagcqcata tcgagccag tgggcaagag aagacaccac tagctgcttt atataccgga atacaagcgg atgatgaacg tggtattgtc agaatccgtc tacacatgct gtCtgttacc aaatctctac CCtggataca acggqaactt ctttgcgacg tttcgcttct cattaaagca 120 180 240 300 360 420 480 540 600 115/282 attttgacgc aaaaaattat caatacccc ggcagcacat acctctactt agatctcaac tttatqtcgc tatgacttca ggctctacac gccctcggac aacgcatggt acaqcgacat tctcqaacag cgtagtttag actgcgagtc ttttggttgc gtgagagagg ctgttgtaa tgggcctcgt ccagaccgct cccagtcacc cctcagaacc ccctagacgg tctgccagat cggtagacat ggtttgagtt acactggatt a tt tt agta a ctattgggta tatcgagacc tgaaatgaca caactacgac acagcgtcca cgtatcaggt gatcctcaac gattttcaca ggatcagtat tactgggact ccgggtgcat ttgggttggg gtaacgggac tctaccttct cgcacagccg caaccagtgc catgcaggtc aacggcacat aacttcaatg tctactgcgg acgttggtga ccgtctaggg aagagcttgg gtgccctgga tcaaccgcgg tacaagaatt gcggcacagt tattctccac atgcaggcca ccaggtttcc gaccgatggc tggataggac catggtctag ggttggatgt tgatcttatt gaatatcgaa tcagatcgca tcacgacgag tgtgcgcgat acggatcctt gggggatgct gagtttgcaa gtataacgcc caatactatt tgcgtttgct 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1329 <210> <211> <212> <213> 79 1839 DNA Aspergillus niger <400> 79 atggcgtcct tcggccgcag atgcatgccg taccagaatc ggatgtagtt gaaaccttga cagccagtcg gaqatgtcgg gaacgcgatg gccaaagcca ctaaaaggcc ttgccctacq gaagttttac ggttgctct C actattatgt gccatattga gccatattgc ccatggacgg cctataatga gaaccgggtt ctCagtt cat atatctacat tccaggaacg tattgattgg catatgaaga agtcagtctg gacgctcctt tttctgagcc cgtccttggt gtcagccaaa tcactccttg ggtggatCCa caaccgccag cgcgttgatg gggttCCtgg cagttatgtc tgtctttCtg tgccggcgag gaacaagaaC caatggttgg a ggcctt at c taagtccagg cccggtgcc cagaaCaatg cggactgtga gaggtcggtc gacgaattcg aacacggaca gaagagtggt tcttacgccg gttCaaggga atttctccta aaggaaggca ctggaaactg ccgagqggcc gaaatctttt tctggttgaa cgtatcqcct ccaatttgtt qctatcttca tcagattatt gtcagcatat agaccatcgc atqaacagta gccggaccgc gcaagaacaa cttgctgaag cttctggcac cggtggtccc gaaggacaat gttcgtcgat tgagctcgat tccggagtat tccatacatc ttcgtggaat catgtcctac gaaggaaCtC ggtccacctc 116 /282 aacgactqcg ctcaacatgt accgacctgg atcaatccgg aatccgcaaa caaatcctcc ctcatcaata qctcctcgac aacctgactt cagagccggg cccgccgact aacagcaccg tacgccaagt ttcttcatct atgagcggaa gaagcggggg gaacactacg caggcctccc agaaggtcat atgacatccg aggacgtgaa agaagaagtc agtccccgcc ttttcagcgg acatgaagtg acgactggag acgtgctcat acatgctaqa cgcqcattga cggcggagga caggcgaagc ggcgcagccg gctctgttct atttcgacga ccgtgggcga gagccggggg gaatgctctg ccttcgtgac gccctatctg tggctgggtg ctcggttcaa agacaaggac gaacggaggc tttcgaaggc ctacaacgca tcgcttcatg cggcgagaag gcaggagaag cgttctcctc ccggcgtcac cgagcggttc ggcggagctc ggacagcqac cagtcataat ttggataaga accaccgatg cagcgggaag gagtgtt cag ctacttcccg ctgatttgca acgggtttcg gagccggcgg agccatatgg aatgtcgata ctgccccaga gagaggatca gtcgtcatta cagggatacc cacaacaagc gatgaccttc gaggatgata ctatcctag cggtcgaaga catgcggtat atgtggttaa gtgcagtgag gcttgctgga accatgttgg agacctcacc gtatctatca ttccctacga tcgcgagcat cqtcggtqggg aggagacgga tcggtgtatt ggggcgtctg gcacgggagg attctccaga tttcacgaca caacaaatgt gaactggccc agcgcttaac cagcgctttc atcgggactt aacggaacag tggcgtctgg at at gccaga ccttcctcgt cggaggcagc cggccatccc atggaaagcc ag tt t gg gg c gcataaggac cgcagacgtc cctcgaaaga gcattct ca a 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1839 <210> <211> 1596 <212> DNA <213> Aspergillus niger <400> atgtttctga tttcacctgc agtgacagtt ggagcaactc aatctgaacg aagtcgggct taccgtgctg cgaccagagc ccagtcgagc aggaccaagc cccacttggt ggaaagctta taCtcggggt cgatccctat cgatgacagc ttccaaccta agataggcga accttcagac ggctgttcct ccgaacaggg attctttcag acctatgcac ccgtcatcaa cgaatattct gaccaaccag tcggaaccgg attttccgtt gcggctgcac gccgctcatt aacacttccg cccgatgtgc aacaatggat gaccttacca gaaaatggca tgggtcaatt g ga aat gt ta ttctgctgat tttccaaacg actaccgatt acttcgatgt ctcgatccct tttacctcaa ggttcacatg tgacgaa cat cagccaccaa caacggcgca tcatccgacg cttcaataat tggggagatg gttttatatc tggagggcca gcagcctggt gctatgggtt cgaagaagag 120 180 240 300 360 420 480 540 117!/282 attgccgccg attttctcga cttctttgaa aagtttgaag atctatacgg gataaagaac tttcgcattt gcaatgctag gcctgcatcg cagcacgctt gaagaatgcg caacccccaa gcctataacc tgggacgtcc aaccgtatcg agctacgacc gactcaccca ct cat tgcca ca qa atat ga attcagatgc ctqgatggcc gagacatatc ctgcagtggc tcatgaccqg acaagaacga gccaatggga cactattcaa gctacaaggc aatacatgaa cgaacccatg tgggctggcc atgtcaagaa tcgtcttcgc accccaccga acgqtgactg cctggaacgg ccgatctcca Ctcagggggt agtcggggca tgttggggca tgagagctac caccacgcgt ctacatccag cttcaatcag ctacttcgat ctactccgag cttcaatccc gacagacttg qgccctgcac tggaggcgac gggtgtcctc ggactacctg ccagctgggc qtgggttgag tatgqgtgta taagcaggct aqttgagatt gccggtcgct ttcaatctga gccqaactcc tcctacatqa gagtactttg tgcgacatct taccgcgtca gcatacgagc gcccccatgg gctgacccgg ccgcgtgtta attatcacca ttccagtccg atttttgagg caacattatg caggatcagg ctttaq atgttcccta gcggagccct ctgcctaccc acgaqcttga cctttccacc ataacatgat ttgatgagtg ct gcgccca c atgtgqaatg gtccggagca ttgaggcgac acggcaccct cacctqccac cccaggaqgq agcgcggttt gccgtgtctc tatctcgtcg tctttatgac Cttcgtcaag aaccacctac aagcggcatc ctactacgaa tccacttctc cacatacttc ggagctctgc gcaaggggat caaccgcgtg cctcqccatc accgatcgat atatqqaggg gatgtgggcg gtatcgccat 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1596 <210> 81 <211> 1596 <222> DNA <213> Aspergillus niger <400> 81 atgctgtttc gcagtctgtt gtcgacggct gcttcagctg ctaaacatgg tcgatttggc aagcgttccg ctaacgccgt gaaacactcg ttgaacaaca agactaagcc ttaccqcgtg ggcgagatgt attccggctt ggtccctatt tttgtcttcc agcccactat tggcgagcct ggccctggtt gcagttccct tgaggccttt cctggaacct accaqcctgt tgagaaccca gtcctagccg caaaaagctc ttgaagatcc gaaagcctgc gagaagggca gtggatgaga ctccaggaga tactcgtggg tctcqctgtg gcgacgccat ctgtcgagga ctgatgttca acgtgtcacg tcaccatctg atggtaqatt tgaatctcac cacggataat gaacatcqcg ctatcagttc cttcgatctg gtcccttttc gctgaatggt cgtgtggcag caatgttctg 120 180 240 300 360 420 480 118 /282 tgggttgacc gaggagattg aaaaacttca tccgctgctt tat gatccet gtccagaaga atccatgagc ggtgtccagc gttaataacg tgccccattc gccagcatct tggtccgagt ggcgact act cgagttctga tcqatccaga atcaacatcg ccacaaggtg gagaccttcc cttgagi ggc aacctgtggg ctgaagactt agatctatgt t cc a gat ca gtattggtca acaatgccct aatgtggata cgccaaaggc ccgtcctgga tctgggacgt actgaccg gct cggtgga cggccaaccc tcggtaacgg acatgacatg acatccctga gtcagggtgt agagcggaca tgcttggccg aacgggattc tgtgaagttc tactggagaa gaatgataca gtttgactac cttcaatttc caaggatit c tatgaactgg tcccaacccg tctiggatic cgcigatgtt gagcgtcit catcgagcat tgattatgac gaatggaaag cctgatgtac catggqcaic catgcagccc gcgggatacc ictctgggtg itcaagaact agttatgcgg gaacacttca gtgcaggagg aatgcaagct aicgaccagt agcgatccca tgcttcaacc cccaccgaag aagcgtgcca gtcgggggcg gtctigcccc atggt cat cc cttggattcq aatgaagigt cagcactaig caattccaac cigtaa tcccaaccgc ggcagcagat gccgttaigt acctaaaagg aagcaccigt ttttggcgga atctagtcit cctgtgatgt cctacgaaat tcgaciatct tgcacgctcc aeggeggecc aggtcatcga ttaccaacgg acacggcccc tcattgagaa agcgtggtct ccagagtgtc iacgtccgag cttigggatc tccttacata tgcaciggca tgttccctit actagagagc cccagcatcc ttatgacatc caacgagatg ccctgcgggc taa catca cc egagcaggag aggcaccaac cacccttcic cagcaccccc cggctatgac tatgtgggct ataccgtcac 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1596 <210> 82 <211> 1479 <212> DNA <213> Aspergillus niger <400> 82 atgaaaggtg cggcgctaat tccicitgcg ctccaiaaac gcgacgggcc igccgtcgtt tccttgcaga aacgagattc tacggicggt iacgcagtca acctgacgii aggaacacct ggcagcagcg acctctgggt gaacaccggc tgcacccctt atggcttgta caatgccagc cacctcaacg atacatatgc ggacggcaca cicacgatcg gcaacacaac aatcgataat gcgggcattc cgtatgccca gtgactttgc gcgcaaaagg aacicaacii gaatcgtcia aacctttacg atgcagtttg cttttgccca iigagcgcag agaactggga tatcattagc actgctcaat ctgtaaagac gtccttatgt ggatcgccga tggcctgtct gagcgcccag tgcgacctat tiggacact cgacaatcta cgtgggcaca gaccgataag gtcaacgact 119/282 00 00 agtaaacgcg gacaaagtct gcgtacagca gtcaatacag aaatactact agtagcttca qcactgccca a cat acga ca agtttctccg ccggggtggc ctgctcggtg atct ct ctcg ggaacgtctg aatggactga acagccacag acgagtactt ccaggacttg ggatcgccgg acgccaacct tatggctaga ccaagtacaa ccctcgccat ccgacagtct gcgacctggt tggcctacat gggcaacgat ccgacaacac atacattcct ccaataccaa ctgtgccaqg tctcgtctgg caaccggctc cctcggaggg cgggtatcgg cgtcggttac ccctcaggcc tagtttqqag gggcgatctg cgcccttacg ccccctct ct caacaaggtc cgactgcgac caccgtgagc gtgtgtcttg gcgcagtgcg tttcaatcca agccacaccg caccgcagtg aaccggcact cgctgcggcg cctacttctc aaqatttcga ctcgtcgaca gcgtcgactg cagact ctt C gagctcagcg qtgtcactcg tacgatgcgc actagagaqg atgagtgagc ggcctcgtgc tacgtcqtgt ggcgacgato gttccctctg cccacgctgt ggctctagcg caagctacga gctctgtaa cctaccaagc gcggtgccat gctccctcct cgatcattcc ttgcgaccga atactggcac tcaacgcaac cggattacaa tgattatccc ctagccagcc atgatctcga atatcctcga ctgtctcttc cgggtgtcac gtqgttcgtc gcaacccgat cgagcatgac taagtctgct tttcggaggt tgtqtatggc ctccaactcc caccatgacg ctacgacaag tgtaacatac cgcaacggag gggcgtgaac gaacaacgaa aatcggaacg tgcaactgga aataactgct ggctgaagcc gaacctgctc 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1479 <210> 83 <211> 1836 <212> DNA <213> Aspergillus niger <400> 83 atgctgtcgt ctctccttag ccaggqagca ccttcgcctg tagccgcgga gatcttcgaa tacgccaaca atcctcaaqg caacgaggtc gatgtcgctg gtttcgaaca agccgtgatg ggaaagcatt tccgcaccca cgatgagatg gtcgactcag tccgcgactg gctggaatcc gactgggtca agttccatac caccgtaaac aagtggtatg tcagcgacgc caagcatatt cccgacgccc tggtctcgca catcaacatg gccgtatccc aagctatccg attcgcttgc gatatgtcca aagcgcatgt gccggtgtcc aaggccaatg cgtcgtctgc atccagccca tcgcggtgtt gcgtccccaa aaatcgccct cccccggaca tgctccccag acaatatcca ccctgctgga gcaccctgca cca cccgctt gtcgctgctc tggctggaga tcagcagcat cgccgactat cgagactgcc ggtcgacgcc tgccgacttc atactccatc tggccagatc 120 180 240 300 360 420 480 540 120/282 00 00 cagcccaacc gcagccaccc aagcagctgt tttgccagct ctggctccca gatcagcttt gtcagcgctc gacctgagct ggaatcctca gacgaacaga ggcagccgcg ct caccaacg tgggtaacct tccqgcggct tacctcacca ttccccgacg cagttcqacg gatgcgagac gtcggaagtg gggaggaatc aatgccacga aaaggggtgg gtgccaccat tggcccagaa acaacatcgg accttgagga atgccatcgg catcgagtga ccgtccccat cccccgaccc agcttaacaa ctatccccgt gcgtctctgt acggcaccaa ccqtcggcgc tctccgacct agcacctggg tctccgcgca ggacgagttg tgagggccgg agaagggtgc ggttcggggg ccgggtggga cgttgggtga gcgcagcaag cacctcccac tgactaccag atacgcccgg ccagaacttc cagcggcgaa caccgagtac caacgacaac ctccgacctc cccctacgcc aatct tct cc ccgcac'gcac aacctccaag ctggccccgc caacaagttc gggcgtcaac ot ccgcgccg gttgcctgtg gttqaatgat cacgcctaat t cct gtgt cg ggagggtggt cccaagcacg tgcqactcca gccgatccca tatgccgatc agcqtcgtcc gccaacctcg agcaccggcg agcaacgagc ccacaagtca cqcaccgtct agcggcgact ttccctcctc acctcccccg ccctcctacc tcggggcttt tacgctgttt acgttcaqtq atggggttct at tgt ga acg ggtagtcctg gggttgggaa aattaa ccgatgagac tcatcacacc agtccggcag tcgagaggtt aattcaacgq acctgcagta gacgcggcga cctaccttga tctctacctc gcaacctcta ccggcgtcgg aattccccgc agcaagccgt aacacgccgc tcaacgcctc acgacaaggg gcgtcatcgc tgaatccgtt gcgggagtgt ttgtgccgtt cgccggattt attcctcacc gcactgtctg caagatcggc cgagcagcac cggcctcaac cat cctgggc act agtcccc cttccttcag ctacggtgaa cgcccaactc cgccqcctgc ctcctgcccc ctccttctcc cgtqcaaacc cggccgcgcc catgcttggc gttgttgaac cctgtatggt gggttgtgat tgctaqttgg tgcgaagttg 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1836 <210> 84 <211> 1437 <212> DNA <213> Aspergillus niger <400> 84 atgtggctct ttctcgtgtg cagtatcctg ctgccacttg caatacttca acaacaaaac caaagaattc gtcgtcaatg gatttcgaca ttggcgagtc ctatgcgggc tacctaccca agtctatact tctqqttctt tccatcttct gatcctgatg tggctgaatg gcggcccagg atgcagctct ctggcaggca gagtagtcaa cgcacagtct gctctgctat tccttttgtc acacgccttc tggaatctcg cgtctgatga gatcaccgtc tcatgctcga qaacggcccc 121 /282 tttctatggc acaaatatgg gtggtctcag acattcgatc at ccca ta ca ggcatccaga gtcaatcagc ctttccgacg tctcaattcc gcttctctag ccctggaacc agtgacatcc atcttcccga cgcgtcatcg ctggcgcagg gagcgggagc ctgggaacgg gaaatcccgg gttgcgaatc aacctggtac tgtacattga aatttgatgt tgcagaatcg tcgcgtcgca tcaatgatcc accgctccct at tgtggct a cat cagtgcc ctctcaaccc cagtcggcgg agaaa qccat cggccaacgg aacagaccaa gaaccctgat cggtggagcc cacatacaga a at atgcacc tgtcgacaat ctaccgaccc tcagcctgct agccagacag aaagatatat gatgcttgac ctacatcaat ctttcccttt cacttcgttt ctataatgct atgcttcaac ccccatcgtt caacgcgtac act ggacaca caataccatc cagtatccag gttgttcgtg gcgtggattg gggqgcggca tattgagcag gtgcgcaacc ggaacgggat tttatggact ctcactggcg caggatgatg gagctgccag aatgacacct cttgacgatg aqctgcaaca cgctaccata ggacttggtc ccaacggact tcccctccaa attgcgcacg aatatgacct ccgtatggtg acattttcga tat cgccagc gtgcagataa cttatgcctg tctcgcttgg tctgqaggcg agagctatgc atgagtattt ttttgcaaga tcatgagtca cccttacctt tctgggatat tccccgacgc coaccaacta atttcgtctg gctccctggg gcctgatgga ggaatqggaa gatcatcggg cagtatttag tggagttttt cagagcagaa gaacaacctc cccgtctacq gtt cat gaaa gggccagtac ccgggttgcc tgttgcgacc aatcaccaag tccaccccgt cat aaacaac ctgccccacc cttcaaccgc caaggatgga accgctgccg tttcgagctg gcaggggttc aggaggcqtg ttcaggacat gctggggagg tggttga 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1437 <210> <211> 633 <z212> DNA <213> Aspergillus niger <400> atgtccaaac tctccgctgc tatctccaag ctcctcctta cccccccaac caccgcctac aaagacacca actgcaccga tatctccttc aacggcggat actacgacta cgcgggctca acctgtaatg gcagtgactc gacactgatg tgtggagatg agagtgattt gttgtttaga gatgtggaga gtccggggcc gttggagatg ctctccctct ttctacaaat tcacttgtct ttccagatgt tttgagatgt cagccggtga ccggtttggt ccaccatagc atcccgccct acccctccct t caa tat cga ataatagctc cggaggagtg ttgagttggg caccactctg cttcgtctac gggtaactgc tgctgcgtat cggctcggat tactgttgcg qtcactattg 120 180 240 300 360 420 122 /282 00 gggaattgtg ttagagacta cacagattat ttagcggctg gtqggatggc aattatactg ctttgatact cacattacta tggtactatg ttqttcggtg tggggattct tgagggtggg gaaatgttat tcatcaaggc tgaatacaag tgtaaccgtg gtctatggqc tgtacqagcg tctctgactc ctacaatgag tgaggacctg tga 480 540 600 633 <210> <211> <212> <213> 86 1827 DNA Aspergillus niger (400> 86 a tgcgtcacc gtccccgccg tcccagccct atatggggca cgctctcctc ctgcgcaatc gtatgggcgt actcccctaa ataggacttg gacctttttt gcttccatgt gaaattcccg acaatcatcg catgtaatgt caggacttcg gaqacggacc atcgatcttg tqttcagaaa cagtgggcgc cactct tact acgctcgaga cacgaaatct aacaaccccg t cttatCa ct gctccattat ctgatccccc tcgaaaaacc cctcccggat acgatgaggc ctactccagc tagacaacct aaggacaatc tccacgagta ttccatccca ccctccgact ttacgggtgq acacgctcat actggatcat gactatggcg accgcgcctg act at gctgg tcaacgagac ctcaaacaat gcctggaaga acqatgtcac ggcggttctt *gctggtgctt cactccacaa iaaggccatgq *cgcatctcgt tctggcgcgc cgaggcattg attcgtagat ggcagagaga tggatttgcg tcagcctttg tgtgcgcatg gagcgcaggc tagccatgcc taccaagtat gatccccacg Caagaatcga gggcttcgaa agacgagccc acaaaacaac tctctacccc gctaggcctt ttctgcctgc ccccattggt ctgatcgcat i ccacccgtcq at ccgcct cc cqattcccac tacggtagtg gcccaggctq atccgactgg atctatacga tcctcgagtc tccgtcatta attagcgttg agctccaccg cgcgaatgga ggcaaatcca atcaatcccg cagcggacca tgggacqgcg ttcgagggaa aatgccgaca ttctcctact ggcctagcca gaaggcatcg ggcaactccg cggccgccct agcccgttca gtgactggat tcaacqattc acgtcgt act cagacattct ccgaggaaqt cctatccatc gacctgcgcc tcccctggat gagtatctta cggcgt cagy ttggcacctc aggccgttac acggctatgt gcctacgctt gtcggacccq tggaagcaca tcgtgagctt cctgctcctc aggccattcg tcacggccag gtggcagtgc ggtctccgcc Ccttctctct catcgagtcc cccgcgcaat tcgtttcagc attcctggac caccgcatat taaaaagccg aaagttcggt gcggctgctg cgagggtcgc ccctcgtaaa aaccgtgaac Ccgccttcta ttatacctgg ctgtcccgga cgctaaccct acaattagca ccttgacctt gatccctcca gtacgcgact tgcggcagat gttggactqg 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 123/282 ttttaccacc tacgggttcc gttctgaaat gaactcttcg gaccgct ccc gaagataagg gatgatgatg acatacgaat aagtgcacgc tccttccgtc tgggatcctt atctgtcaaa cggcgtatct aatqggtaat atgaagaaga ttcggcgacg gact tat tca tgaacacatc cct cat cgga ggacgaatcc acacaacgcc ggtggaggaa ggaagagqaa acgctga taccagatca atccccaccg ggcgactcat gatctggata aacggccccc gaagactaca gaggaagata agcttcgtga gcaaggagat ttgacqtcga qccgctattc tqcccaacat cagacgatga cat at tgggc tcgcgqaagc ctacaatgtt ttgggaatca aaaatccaat tgacgaagac cgacgacgat caccgaacac 1440 1500 1560 1620 1680 1740 1800 1827 <210> 87 <211> 1251 <212> DNA <213> Aspergillus niger <400> 87 atggctttcc gccacagaac ttcaagtccq cacagqcgca agaacgtaca gaggagatcc gatacgctag gggtctagca gtggacaccg aatqctgcag atcgggggca gtaggtgaat attgtgagca tcctatgcgt gccgctggaa attactgttg gtggttgaca gccaccaaca tcaaacgcat aggtccctca gcattgacaa gcttaqaagg gaattgccaa gcaaacatga ttaccgaaag ccgactacat gcatcttggc ggggtgagca aaacatacgg ccagctcgac agaaccggac ttaacaatgc at yagaa tag ccgctatcaa tttttgccc cgatctccgg tctcccgctc tccgaccatc tgcgaagatt ccgcagtaca ttttgctggg ccatgtagct gcgagctcct ctatgatgac tacgcataat cgttgatgat ggtttcgaaa atcggtcatt cagtaaggcg agttgagaat agatgcagca cagaagcaat gggagagcaa cacgtccatg ictggccctca cagaccatcc gagtctcatg accgaagatg tacgcggggt tatgtggaac tggggactgg agcgctgggg gagtttggtg gttggacatg aacgctcacc ctggatggct gcgataaata gcttttgacg cggactagcc gcccgtgcgt gtactttctg gctacacccc tcttacctgc cggggaagta ccgcatgqqt accttcccgc ctttcgatga aagatcaggt ggagcatttc agggtacata gtcgtgctag gtacacatgt tactgtccgt tcaattgggc tgagtcttgg agggtgtgct cggcttctgc cat tct caaa cat ggaccgg atgtgacagg agttttcagt cat tgt tact aacggagctc cgggatcgaa gaaaactatc ctggtatctc tcaccgtggt cgcttatgta cctggcatat agcagggacc gaaggtgttt cgccaatgat tggaggctac Ctcttgtgtt acccgacgcc ctacggctct ctcgaactcg ~ttgatcctc 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 124 /282 tatttgatqg gcttgcggga ccttgctacc ccagcggctg caacgaccga gctcaagagg ttggctacgc ggaatgctgt caccaatgtg gcgggtaqcc ccaatcttct ggcctacaat ggaaacagcg gcgtgtcaaa agggggtagc gatgatggag atgaggacta g 1140 1200 1251 <210> <211> <212> <213> 88 1368 DNA Aspergillus niger <400> 88 at ga tcaccc ttagggccag tcaattcgca ggttggctcg Cccttccatg ggacLttcg aacccctggg g ggtt t tcc t gacatgcatc cccgttcacc atct tggaac gtgggtaacq actactaact gcgaatatgc atatgtcatq ttgctaagga gcggctctaa caacaggtta gcggacggca ttcttagcgt gcgaactcgc gaaattcagg ttttgtcggc agggggctga tccaggagca acattggccc atcccctaac aagaagttgg cctggaccaa atatcgatqa ggttcttgcg tttccggtga aaaatgaact gattcatgtc caggagt ccc cgcactgtat cggcccagtc tgacgacagt ttgagagata ccgaataca a tggtgtcgag atcaagqcaa tttcttggaa tttcggtcgg cctgttcggc tccctttacg gaatgactcg gaagcatctt gctatggatg cccttgccgg gaattcatca gggctatgag att at tcat a atcttacgca gt at aa agat acccaaggat atctcctatc ggatctatat cgtctgttac cactgcacct tttgaattcg attcgtcgct ctcgaagcag ccttgatctc aggccagaca tgaagggacg agcgtagtat gtgtttcgca atctgtgatg ttcttttggt actgggggcc attaatgagt cttctttttg ctgcctcatg tccgagattt ggccggtaca agccccagga gcaacgttcg ttcaatgaaa gacatatgca gatagtgttg t gt gag at cg ccatctgttt acttctgtta atcqctttct gcctgtaata gaatttaccg gacgaaacgt atgccgctac gcccacactc ctcgttcacc attttgaaag caggagactc ttgggaatgg ttgaccagcc actcacgtga ttcctcacaa ttCcttatct taccgctqaa ggtattggga ctaggtgcga ttcaacactc tagggct cat acgaaatgtg gggagqccct ttgatgcatt tactcgcaaa cgqctggcaa caaagccctt cacgctttgc gcagaccgtg accggcattt ccaattcact ccagaatgac gagtatgatt aacagatcac agtcgatgtc agccgcggtg acagttcctt ggcqacccaa atcgtgcttg aacactgtgt tat tatggcg agaccccgcq gqccaaatta ctatatcgaa gtcgccaccg tgctcaatca taatgttgac cctacgttgg act tccgtgg Ctttgtgact 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1368 gtggacaacg ctggacacct gttgcgggac tcaaagattt caaactqa 125/I282 <210> <211> <212> <213> 89 2376 DNA Aspergillus niger <400> 89 atgcggtttc aatgtacaag ccacac CN1 aatattcatg ocgcggaagacg Sattgctccac atgtggqatc tttgagggag atggagaaga ttctaccggg tcgacctcgt caaccgtatq ggactcaaca ctggcgtcga ggtgttgcaa tgggtcatca attgggctgc acggcatgga aagtqgcgcg acqggcaacg gatggctcga cagatctttg acctgcgcgg aacgccaacg caatgcacta ctctccgcca gagtccggcg tcacttattc ctcgatcaca agacaccctc acaagcacca cat ccgt aca atgagcataa cggtcggatg tcttcagtat aacgccccgt attcggatat gtcaagccga gccaggcaga agcgccaatc ccattggtga cggactgcgc gtactgtcaa ggaatctgac acatgccctg qtgagcaatc aqgtcggact qcacggtcag ctca tgaatc aggatctcga qgaaatacat tcggaaatat accgqacqt aagactgcga cctgcccttc agctccaagt acagcgggtc gcggataaag qtatctcgac ggtcttcaag ggcgcggatc cgacggcgac ggatgtcgac ggtgcgtcta tcagctcggc gaccgatacq cgatatcgga tacttcgggc ctttaccggc cagcgcgtcc tatcaccgac ctccagcggc ggatgacaat gtcatggctt tggaactaac tggccacacc agcctcgtcc catgaatcct atqcgcagcc caccacctac ttgtggcggg attgcaagtg gccatccgtc gatcaccttg ctggagctgg gcggacggga gggaggagtc tact tgaagc aaccatcacg cttcccgact catacggaac ttcaacacta tggggagcaa agtgtgtctg tgtccgagta tcattcaaca aatgtctacg agctcatgcc aatctcacct gcttattgga ggccaactct gtcgtcgttc tttggcgctg cagtgctgtc acaactggaa ctgggccqca actggcagcc gaagatggtt ctatctcgct atgtgtcgac accactttga agcccaacca acgtgcgacg tact cgggcg aggatggctc ttcagctgaa cagcqactga tcaagcggtc accccaacca tttcattgaa gcaatgcgqg cgaagcaagt acgagactgc aaaagtcctt ccgacaaccc cccgactgga ccctgatgag qcaatagcga ggtcttccgg tccacgactg cqttgacctc cagacatcac acagcgttaa agtgcggcaa gcgqcgacaa ctttggggtc gcttgaccaq catcaccttc tgacatcctg gcacgagccc aggaaaaggc agagccacta atcggcatac ctatataatc gtcgctcgga ccctgtgcta ctccttgttt cggagtcaat agctttgatt cgccaaggaa caacattacg gcccgcggcc tctgttttcc cgattgcgcg tgcttcttcg ctcggattgg tqactcccag gagcacctgc tgcgttctcg gtccagttgt cggaattgtc caactgctgc 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 126/282 gacgcgaaga tgttcaagct gacgtggcag gacggcacga agccgcgact gcctgttcct tgctacagcg agcaacggcq gtcattggtg gtaaaccgct ccgtggcccg tatcaaggct ccgcaacata catqcaaqtt gccaattctc agacctgcag gctgcggcag accagtgccg ccttcagttc tcaaccaaaa actgcaaggg tcgcctgcgc gtcgccgggc gcgctaggcc tagggaatqa tgcct cccca caagtcggga ctcagctggg cggcaactcc cagtggctcg cagtgtgatg ctcctgcgaa cttcctcgac ccaaaacgtc cgtaggcgcc tcgcgcgcca tcccccgccg qccqcccqccc ggggcggtac gctgtgtgtg acggtatgtc agtacttgtc ggacttgcct ggcagtct cc ctggtctgca ggcactccct gaatcctgga ctgatccttt aaacccgtcc ccgcccatga ccgtatccaa gcttqa atgactccaa gtqccagtcq ctaccgactc gcgctagtgg tccacagcaa cctccccgaa gcggtagtgg tcaagaacca tggccctgat cgcgt ccagt accagtggcc atatacctao cgacagctgc cggcgactgc gttcaagaag ccaatgcacc cgacacctac gatcggcacg cggctactgc caaaggtatc gacctgcatc gccttacggg ggcgcgaggc tcaaccacita 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2376 <210> <211> <212> <213> 1446 DNA Aspergillus niger <400> atgcgtttcc ctccagccag tcgatccgca ggctggctcg cctgccaatg ggtctgtttg aatccgtggg ggattttcgt gacatgcatc cccgttcatc atcgtccaac gtaggcaacg accactaacc gccaatatgc taagcagtgc aggaaccatc tccgccagca acatcggccg atcccctcac aaqaagtcgg gctggtcccg acgtcgatga ggttcttgca tttctggtga agaacaagct gctactattc ct ggagt ccc cgcgatgcat agccctattc cgacttccgt gaatgaatca taaacatct c tctctggatq gccatgtctq gaactcctcc aggagaggac gt tg t ttgt C atcgtatgct ctatcccact tcctcgcgac cgagcccgtc ggaagtatcc ggcctggcgt acattccaca atctgcgctg ttcttctggt acaggagggc atcaatgagt ctactatttg ctgccgggcg tcggaggttt ggtcactatg gagccccagg actacctacg ttcaaccgaa gacgtatgtg atgcctccac gcccatattc cccattccgc act ttgagag caggggggtc acggcaatgg tcgatcagcc attcgcatca tcccgcaatt tcccttacct tccttctgca gctactggga ccagatgcga ttcggaaccc ccaggcggtc cccgcaccac ccaatacacc ccagaatgac cagcatgatc cacttactac agtcgatgtg agctgcaatt gcagactctt cggcagtcag ctcatgtctc aaccctctgc catcatggcg cgatccagct 120 180 240 300 360 420 480 540 600 660 720 780 840 127/282 atct gccatg tctggtgaag tgctacatcg ctatcaccac ttcgatctca aatcaggtac aatctgcgct ctgcqqccat aaggagqagt gatagacctg gagtga ctqcgtcgga gtggtcggaa aggccgctcg ccaaagaaat cttcagacac atttcctggc qggcgcattc gqagttgggt cgaggtttgc atatcgcgtt ggtatgctac taggtttgat cat cgagcag caaagaatac gatgacgcca gtatcaggqc tctgccatgg agatgtggta gctagttacg ggatatgatg gagggcgtga ataaccgctc tacctgaaca aaggttactt gcgtctgagc aatctcgatc agaggtcagg tctggaaaag gttgatgggg gtgcgctgga tcggatggta cctgcgccct cacccgcagt ccgacaatgt aagtcgcgtt tgqcgtgtaa tcgagttcgc gtggagtggc cgggacattt tatccggggc tgatgacgag tgacgqcata ttgggctgct gtcgcgcgca cctgcttgcq tacggcgggt gtcgaaggcg tgqaacgacg tcttcctcaa atcgtt tact 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1446 <210> 91 <211> 960 <212> DNA <213> Aspergillus niger <400> 91 atgacattgt accagatgca tcactccgag gaggagagoc agcaatgaag cagaaggcat aatgactcgt aattatgqca tctcggqact actgtcctag agctacatca cagtacaaca acgttcgaag gagcaatctg ggccttgatg tact caactt gcgcactgct cggagcatag gggaggtggt cagcaaacac atgaaagtgc gggcqcgaaa cat taaatgt atccaaatga qcttctgtac aggatggttg aaggcggcac gtgaatcgtg agcctacgag ctattcataa ccacqcgctc tttacagtca ttcttgttgc caatctttca ctctggacgt gaggctgtat gccttggatt agtatcagac gactatcacc tgatgatgaa ctatttccaa cggtaaccga gttgcctgac taacgtgtta agcggtt cat ctcccctgat cggatgtccc ttttatqgac gacttttgct gatgtacagg gaaatcgaga gacatgatca tatcggttgg ctgggqatga acagatctcc cgaacagatg ccgagtgtga gcggatatca gaggttggcc aatgaaggag gccgagaaag tattcatctg ccacgccagc cccaacgtga catggtttca ccagccagct agggcataac agaatgccct aggcgtcatc tgtcagatca attccagcag tgccgggtgg attggaatgg attacattga attcatgccc atgactgtta gcccggtgag cagcaccgcc tattgtaagc ttcctatctt tcgtcacata acgaaggggc cgacgagaat at cat catca ccctcgttcc tagtttagcg gctgctgcat tgacaccccg cqatcttcct tgagagtttt 120 180 240 300 360 420 480 540 600 660 720 780 840 900 128/282 actccagatc aagcggagag aatgaggagt atgtggtccg ctatgcggga agggaagtga <210> <211> <212> <213> 92 1920 DNA Aspergillus niger <400> 92 atgcatgtct aactatgttg ctggacaaag ggccatgatt tccagcgagg cacttttcct ttcatgagcg gtgccctact tattgatgga aggtgcacga actcagtgtt acggcagcgt ttgccagccc aacaccccat acctggattg aatccgccgg tggctacagt atct aca ccc gaaaccatcc ggcacgccct ttagcaccac ctggcggtaa acaaaqggca ctcaaccttt gactccatcg ctggacttcc gacgacccca gccatcgacg tccccaggcg tccatctcct cacgagttca ggcgtcgcct ttcccagcca gacgcagcca aatatctacg agcgacgacc tcgatgccca atgccgacac aatcgcacat ccaaaaagag taccaatcaa ccccagactg acgagctcgg tcttcgccaa acggcgccac aaatcgccta actacqaaga gctcctattg gctactcctc acggcagccc tgaaactcgg ccagcacggg catgtcccta aggaccagga cccgaccatc tcacctaccc gcgcgatgca gcctatgcgg ggtgtctcat cctatttgcc aattgctcca tgcaagcgag gggaagttcc cgactacata agatgcagag tat cacgaag cattcgagcc cat ctt cgag ctttgccagc cgccccaaca cccaatcatc caactacaac caacgaaacc ccccaagcaa cgaagccgac ccttcagggc cacctgcttt tctcaccgca aatagcagtc ctaccagaac ttactactcc ttgcccagtg atagggctta ccacaatcgt ccgtcgaatg agccgcatct gttgagcagc catgtgacat acaccaggag aagcgctctc attttcgacg atgtacaaca gacctaggag gacatcccac gacgtcacca tggccccaga ttcaaaggac tcctctctag tgcggcgtct ctccccatcg atcagcgtgg ggcgatgcag gtaggaggca acccgcttcc cactccgtgg ggagtaaact tctgggtaga ctcagtccaa ctcgctacgq aggccgtcga cgcaatcata ttctgcagac gccacgagta taaagatgct ttggcagtct acccgctagc tcaccaaagg acatotacag agggaaccca acgccggcc~c acaccatcct tcctcaacaa accctcaata acacccccac cctaccaacg tcgtcgcatc acaacgtctt catacctccc cctccggcgg agacctattt acacagactt agaaagccgg cctggatcgt aaagcatctc gaccgtccga caacaagcag ggaatactac ccatgtgccc ggaagtgcgc gcccccaatc acactgcgat aacaacagcc ccaagatgac tccaaccctc cgaatccgac ctaccaaacc cttcctctac cccagatccc aaacgtaatc ccgccaatgc gggcgactcc cgtcccagat cctaggcgca cggcttcagc ctccactacc ctccaacaca 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 129 /282 gatggggtat atcatcatct gcgttcgcgg gtggggtttg gggtcgaatc acggggttgg acaaccgcat acaaccaggg ccatgttgac tgaacccggt ccgggtgtgg ggacgccgcg cggacgagga cgaagcgaca gcgcattaac gctgtatgaa gactgatggg gtttgaggat taccccgatg ctggtgggtg gagqagaggc cat cctgagg ttcccqgttg ttgatggata tttcagctat gtacgtctgc tggcgaaggg cgtttaggga ctggggggtg tatttgtggg cgcagacaat cgcggcgccg gaagtccacg tgtgactgtt ggatccggtg tgatgattga 1620 1680 1740 1800 1860 1920 <210> <211> <212> <213> 93 1116 DNA Aspergillus niger <400> 93 atggcttcca ttggacctaa gacaccggat gttagcgggt aacgacagca acggttcccg tgggcggcct aatactacga gccatatatg gtgttcacct aagatgctct aactccgatg ttcaacgtcg gccctaacgc ttcaatgata aatttgaccg cccttcaatc tatgctgtat gctcctttga <210> 94 agaccctcct atatcaaqqt cat caacact act cccga ca ttgcttacag acaccaacgt tagcagccga cagccgtcga caggttcagg ttggtggcag ccccctttga gccaqgccct caggtgcttc ctttctcata catggtcgat gtgatcagct catgggacag tcgacttcgg a ga agg aat a actcattccg gcactggcca cagccgctct gggaagtgta agaccttgga ctgggtgctt cggctacaac cggaggcact ctcatatcgc tgggttcatc acagatgatg ggaatcgacc ccatgaggaa aatatacaaa gtcaagcgac atcgataagc cgctgacatc ctcttttaca ggccgtgcct ctacaacacg atcattcgac cctgccgagc accccaggtg gatagcaatt ctcacctcta gtcagcggct cagagctttg ggcctggcat caggatggac gtgaccaacc acctatgcgg aca aatct CC gtCCtgaact attcccaaCg tcatctggat atgggcttct ggctatcagg attattggtc ccggagacat gcttga gcccgtttga gtacagatga ctggtgtcaa tcactgccac ccgtcattac cgtctaccat ttttggatga ctaatccgga acggggaact ttggaattca ggtacggcca accagattga accgacctct atggcgaggg acgacgacca agcattggtt acgatatacg tttgatgtac ttgtccaaat cttaggtgtc gga tat tCtC cgacagtacc cgcattcaag acctcgattc gaataatggc gcaatggatg qggacacaac gactaatcta ggcgatgtat gtgctccgat tgtcaccttc ctgcttccct qagcaatttc tgttgggCtg 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1116 130/282 <211> <212> <213> 1245 DNA Aspergillus niger <400> 94 atgtttccct cccaccagtc tacgggtttc gactggacct acctacgatt atcaaccaaa gagcccgcag accaccatcc ggagtatatg taccaaggat gacaatgcca aacacctctc aacacgctgg cgcttctcta caagccgccg tacggttacc ccaaataacg ccgctgcggt gtggaggtgc ggagcgatgg gactttgaga gctctcgtat tgqccaccac ttactgacat ggaccggcca gtctcaacgt ctgaccagta cagccgatgt aagcagccaa gactctcacc ggaggagcgg ccaaagcggt acgtccaggg act ttgtcta tcggagacga ttgccgcgtt agcgtctagt gtgagcaggg atgagtttgc tggcgaacg taatgggaaa agttgcaggt ttggtctctg gcacctgcaa agcccttgga ct at gtggtg cgatcagaaa tggctatctt ggcgacggac tttcgtcttc tgtttttcaq cgcctgqcac atgcagtggt aqatatcacc tgcgccagcc agagcaagag cgaccacgct cgagctqgtc attctatcag cgggtcagag aaccaataaq ttttggcgag ggggattgca ctcgttgcag tcggttgact act ccgggtc accaccttgt attttcaacc tactgggatc atgctgcgca aacgagacta ggtgacaatc tctccaattg tacgacggcc tggtacgaca gtgattaatt ctcaacaaga tcqtatqqtc ggggcaaaag ttcgattgcc cgggcgtggg tgcaccttta acatttgcca gacttcgcgt ccgccaccgc tgcttctgac agagcctgcc gctacaacga agactttgtc ccaaccactt tcggtcccac ttagcgcatt gatccgtgca tctcttttat ttcagacact tcattgtcac attgggcgtt ccactactct gcqgtgcccc ccgtcacgct ggaactcgag agattgtgcc atgtacgcac ttgataagta ggtaa tagtgctgta tcgcagttct gtatctggtt tcccaccgcc atccactttt ctactttacg cgcggtgaac ccctttctcg agcgtccttc ctactgccac aggcggatac ggaggcgatc gaacctcacg ggatggaaag agtgtctgtg ttccgatcct tttactgcca cgagaactat cctgggagat tgtcatgttt 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1245 <210> <211> 1443 <212> DNA <213> Aspergillus niger <400> atgcatctcc cacagcgtct cgttacagca gcgtgtcttt atcccataca ccatcaaact cgatacgtcg gacgacatct cgtcgtttcc tgccagtacc aaaaccaagc qatgctctag gcgccagtgc cacggctttc cagcccgtga ttcattagct cagacgattc cacctcatct 131 /282 gccagcgatg ttcaagattg ggtagcgaca atgttgctcq ccctgcacga gaagagtgga ctcacgattg aacttcgaqt tacgacaacc gttggcttcg gacaaggaca tggcgcattc tcagccatca ctgcacagtc acaacta ct a tacgtgggag ggtgatgaca tacgatgagt tctacgagct acgacgagct attcccgctc tag agtccctgtc tggtagcgga tttcatacat acacaqgcgg tgcacaatac gtgtgggcta caaatgtcac cgtacccaat caacattcat ccctttcacg agtacaccgq ccgtggac-a tcgataccgg tcattCcqq agctacaagt caacttcaqg tctggctcct tacgggtcgg ctgqaacaag ctgctagctc ctcagtattt actgaacatc aactccctct ctctgtcgtc ctctgatacc cttcggttcg tggaactggg tgtacgcatg ggacggcatt ggatgccgtt tagcccgcc cgatatcacc tgtctatgtt aacttcttat cgccaaatct ggcattctct ttctggatgc gggtgacacg atttgcagag cagcacctcg tagtagttca cttCtctgct aaaaggattc tggtctaaca aacattgggt tgggttttcg gacgattctt tctgtcaqcg actttcggac ctcggtCtcg gcagaaagta aaggatggca tacaccgata ggcggcactt gctatgctgc tcggggagct ggtqtgaatt gtttcgaaca tttctcaaaa cgttcctcga ggatccacta tctgatgctg ctggcgattg ccgttcgtcg ccgccgCtct ctgatgagaa gttccaactg cgacccttga qcttgctagg ttgcttccaa gtcgaaccaa acgttttcaa cggtcagctt ccgtcggatc catgcgattt cttcaagcga accacattat acaccatctc ttatcagcta atgtgtatgc acaccacctc caacgggcag aatcaggaag ctt cctt cat tgacaatgat cgatcaagat at ctatgta c cacgtccaca aatgacatcg aaaagacaag cgcatcggat cgatagttcc gtcgaatatc tggcact act ggacagctat ctccaacaaa ctcgaagacg tccgtgcaaC gccgaaggac cgacttattt tgtgtttgac tgcgtcgaac ctcaacgact tagcatgacc gctttggCtc 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1443 <210> 96 <211> 1401 <212> DNA <213> Aspergillus niger <400> 96 atgacgtctt ctaccttgcg ccttgccgtc gcgttggctt ctatcgagcc agcgagatga ttcacttgtg gttccatttc qtccatattg ccaagcqgga tagctccaaq acagtagaag gacagctact ggatgaacgc ctcaattgga acccctgcgc gatcttacgc gctcaagggt cgagcccgca tacaccctcg tgtcaacttg cagcagtgcc cttttggcaa tcttgaggat ctcctctagt gatatatggc agtcactaag tttcctacta atgagaatta cgaatgttct 132/I282 gacgatgaac cat ctcacct actcttggag tcctacagct cqcggcctca cccagcatca tccttcgcag caactaacca atgctcagaa accgacctta ccctgcgccC ttctctgtgt ggcattcagg agacggatgt gatgatgatg ttgcctagtg acagggacgg gtgccgacgg gctgttttgc tctgctccga acacacagag at cacgcaa c ccctcggtct ccacctcccc tctttggagg accacagcat ccaacaccaa ccgaagaact acataaccat gccaggaaac cctgggatga cccaggattc atgtcgctgt atcagaatgg ctgtcgggga cggctgcgac gtctatcaga aggctgttta attcggcttc acacgatgca cgacaatgtc ctcctccgtc atccttcagc catcaacacc caccaacaat cgataattc aatcacctac ggacggcgtg cgaatctcac gctcttcgtc a ga tt aca aa ggattataat aggtgaagat ttggccggct gttgacattc gttgggtagg 9 tacaaaccca ggtgtcgact ccactggaca aacaccagct ctaatcggcg tccaaattca ccattcgtca acctacccta ctccccaact atctccactt acaatctct c ccgtggacgc actcgtgcgg aatcagtttg gagattgtgg agtgttacgg acgacggcga gcgtttttgg ccgattcatc actcctacct tgtatctttt tcccctacat acaacggaaa acgggcccct ccgtcgaagc ttccctcctc cgaccgtcca caagattcta tagccatcgg gtgacggact agctgggtgt tggqcgttgC agattggcac cgtatacgcc cgtctagcqg tgccgggggt cacttatcag tgataccata gtcctacatt cctggtcgat caccaccacc gcaagccttc tgactccctc cacccccatg atccctctac cggggtcctt caacatgacc atgcaagttc tccctttctg gacgctgaag tgggacggcg tgctgcttct gggaggtgtg gctggqgatg 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1401 <210> 97 <211> 1632 <212> DNA <213> Aspergillus niger <400> 97 atgatgcgac cgatacttct ccccctactg aatccctatg taatgagctg gtcttcccaa gtatccatcg acgtgggcag caaccagcag gctagcacga tcctgatgag cactctctgc gctgccgaag caggcacgtt caaccaaaac tcgtgqgaaa caacttactg ggccgtcgag gaggtcacct tagggtcgtt tgtcgtcccc ggggtatttc gcctacggtc acggtcgatc acgaacaaaa acctccacca qgtggaagc aatgtgagct tgcagacctc cagatggccc tttaccccgg ccctgt cat c ctgcctacac aagaggctgt tcgaagccat ctcggcatcc gtggcaggcc agccaactat cacctgctac caccgccagc gctcggcgat ctaccagacc 133/282 taccagacct ggtccgt act cttt act cgt cccaaaatcc gtgagtgcgc gggctgggtg ctccaaagca atgtaccttc tccagcttgg tccgccgcat atcaagattc gtcacctact cagtccgcat gcacaggccc acgtcgcttt aaaacatccg attggcgtcg ttctgtcttc atgtttaggg gatacgaaga gagctggggt atcccaatgg tgtcggatac ccaacgacat caggctccct agggagtagt ttgcggcggg gtggttcggt cccaggcgac ggctatactt acctctcctt ccttttccca tcccgtgLtt tcgttggggt ccggcccggg ctgcctctaa acaactcgag gggtgggtgt gccgtcgccg gctttgcgga tgcataagcc cat cgcctat cgtctccaat tccgtcctac gatcttgggg gtcttcgagt ttcctct ccc tcaggccaag atgcgatgcc ctgqgacacc tgtgttcaac gctcaatctt U U U aU L aU gaactggttc ttacgccagt cqgtacctgg cagctccaag cggtggagca cggggcgagt gctaccgqqa gccgcaggaa cctgtctcgg tcgacggtcc tcgtacggca ggctacgata ggtcttttgg ttcagcttca accgtccaga atcacctcca acgagcgatg atgaatgggg acgctgcaag tccaccccgg aacgggaaca gaagacatca gaagagacct agtqgcctgt gtgttgatcg caagaggcgg ggtgctcaca atgatggctt tcggcagtct tgaacatgat tgcatatcgg agagccgagt aacttgaatt acaacgaaag ttgatccaac ccatgccgat attatctgaa tcaacaacaa aaccgctggt tgctcggtcg actcgggcac cccggatcgc gqqctacqta cttccggtgc cagcaggtat ctggagaqca qtqaaccggc cgcaggaggt ggccctgggg cgcaggatqg gtcggtagac gatcggagac aaaggatatt tggcttgttt caagccctac ctccttcaat tatcacgtct gaacattacc cgatcaaaac agcctttctc atggtttctg agtgagtgac ctqgggcatc caaaattgga agccattgca acggaqgtcg gaaggagttq agagcgatac 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1632 <210> 98 <211> 2535 <212> DNA <213> Aspergillus niger <400> 98 atgcgtctta caggtggtgt cgctgcqqct ctccatcccc atcgttccta cgagacccat acctcgccgg ccgacgtcgc ccaacgacta ttaccctcac atcatacctt ctcgataccc ctqgatcaat tgcgcgatcg tcggaggtta cttccctcct tggtcgggcg agacgaaggt ctgggcctct gattacttcg ggtgctcgcc cgtgaaaaca cgccgccgct ctaggtggca gcgctgctgc ctctacacct acgaaggccc gtgacgatgt ccggagatga ttctttggtc ctccgcttct tgatgaatcc cgtcggagaa ccatgcgctg cgccgctqtc cgagaagctg 120 180 240 300 360 134 /282 gctccccaga gtcaacactc ggcatcqcgg cat gat ct ta gctattgtcg gcgggttctt cgccacggta ggtgttgcgt actgatgagg tggggtccct atggtcaatg ggtaacggtg agcatcacgg tcggcgcaac gtcggcacag gcgqaaccg tatttgatga aagaacggga gtgaaacqggg cagcgggttg acggaggata aatgttaacc gtcagtcacc accttcatga aaggacacca ggcgaggcga gaccacagct accgagctgc acatccqcga acccctagta gaaagctcca agaatgaccc accccatctt acgtgacggg atgacggttt atgactataa ctagatgcgc atgatagtcg ctgcggctat atgacgatgg gtatccaaaa ccattcatga tgggtgccat tggtggttgc acaagtgctc tggcgctggc ttgaggcggc agaagttcag cagagacctg agcatgagat tgttgaaggg acacccgccg tcagtacgcc gcgttgctca atgtcaacga ttgacggagc atgaggaagg ctgacaagcc tgccgaccgg cagaggcaag taaaagagtg ccaagcgctt cggcgaacaa tatctgg btg ggacatgtac cgacaaagta gggtgaaatc cat cgctggt taactacgcc cgccacaatg tggtcgtggt cgataactgt tgatcgggag ctacagcagc gactacccat cctcagtgtg agtgcctgtt ccatgactgg ggatctgqtg cccacagggc aqccaacctg aggcgatctc ccggcggcca ctggggcgag gcatactggg cgagcagcct aaacgtggct cactggtggc tagtcttaca ctcaacacca ccgccgacag gcggcgcaga tqgcatttgt gagggcgtta agcaacgatc ccagagccga ggtgcggcga at tcgga tt c tatcaggaga gaagccccgg ggaaaaggct aactttgacg qqtaaccatc ggcgccagtg ggtggaactt cgqccggaac catgaaqatg ggatatggta aagcctcaag gagcagggct gaacggctgg agcgtggagt gataatcaag tccgggattg caattcatcg ctccacccca accacgagca gttgatcgc gagcccatcg agtccttct c gatatgctgc aacgcattgc ataatactgt cagggcaggg ttaggccgaa ggccgcgctt agaacgacgt tctccgcacc acgatatct a gcaccctgat cggtttttgt gttacaccaa ct ccgtatt c atgcaattca cgqcggccgg tcacctggcg atggaagctg aggtcgacac cctggctcca tggctagttc agcatgtcac tacggagccc aggtgggcta gcaaatggac at tggcga ct tgcctactga tcagcgccgt cggtgaacgt atgatgaaga cagatcgccc ctcggaattg tcagttgggc tgtcacgacg ctattttgcg gagcgatgac gtgcggggtt cat tga tgac ctcgtgttcc caagcgggcc gtttgcggct cagtatctac ggaatcctgc taccacggac cccgctcgct tgacgttcaq gcaggacact atatacgctg ttccccctgg gt acg a ggt g ggtcaccatg tgacggtcgg tgttgactgg tgtgattgtc caacttgtgg acacgatgac tcccacgaaa taagcctaca act ccagaag 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 cgaccaccgc gtcagatagt 135/282 atcctgcctt gctgcgatcg cgccgcaaac gaqgatgagc ctgtacaatg gaaccgtatc cat tctcgga cctt ctt ccc gctccat cat gtattcqcga tacaggcaat cttttgcggq gggatcgggg gatga <210> 99 <211> 450 <212> DNA (213> Aspergillus nic <400> 99 atgaagacct tctctaccgt cccgttgaca gcgctgaagc gatgtlctctug gagcttcctt aataagggct actccaactt accattgcag gctggaactc cagacagtca acattctggc gccatgaaca ccctcaccaa actgaggtgg atgtcagtct <210> 100 <211> 891 <212> DNA <213> Aspergillus nig <400> 100 atggctcaaa tattctggct aaccgcaccg aggtggacct atgccggttg tattcgccgt gagtacggct attacccagt gtgtccgact caacaaacga aataccactg gcagctggga gaagactcga gatactacaa agcctcaaca tcgacaaggt cacgttcggt tgtgttctgc cgacagccgg gaacggacgg cqagagcgat gatcagcggc 3er cacctctctc cgccggcacc gaccaccgtc cggctccctt tcccaactgc cattgattcc caaccaggcc ttgcgcataa rer ttcactcttc gattttccca tcaagcccct aggccgtcca aaccact tat gctgttttgg ccaatcctac ctatgagggc gcgtcgaagc attggcctgg gatgactacg tcgaaccgtt gaggaaccgt gaacaagaac ct cgctct ct accgtctctg tcctgctcgg ccgggcttcc ggcaagtgct gcacctggtq caqcagctgg ctgcttgtct agaaatgata tccgtcgccc aatgaaacag ttcagtgtct aggctgagat ccctggatat tttcactaca ggacgcaagt gcgtctactt atttcgagat cacgtcgccg tattcagtga gggagggcgc tctcctcggc tctcatacga acggtgccaa ccaagattqg acgccctgac gcttcaacat gt cqtat cga cttgggtcag cctttgcgcc at aaagttaa ttattggcca ctggtatcgg ggaccaattg :ctccccata cagcatacaa I ttggatctac ccatgtgcag gatcgaggac gggtggcgag tgaggatgat agatqgagag tctggccgca cactgcctac cggcctgatc aggcgcccct gtacaacggc cgctctggag agctacctat agccgagtcc aatgcctttq ta cat acat c gaccqaccat .agaacgttc ttcaatctca catcgacggt gtcattgtc 2220 2280 2340 2400 2460 2520 2535 120 180 240 300 360 420 450 120 180 240 300 360 420 480 136 /282 gacagggtta aatagcgaga aggattccac gccgatgcca gaggttgagt cccgctgtqa ggccatgctg ccttcagcac actgcgataa cccagttacc ggctaaattc ctaatatcct gttgcaccac tatggcttgt tcgcgaagat agtctcgtct ccaagaagat aacttcaact ggccaagatc tgaagaaacc cat tacgct a gctagccaac cttgctctat attgataccg tcaagcccct gcagacaatg aaggaaggca gcttttgcct ccaacctcac tgtcgattgt tgtcaatgtg gcagcgttag aatgcaataa gcgcgagcag tccttttcta gaccctcacc ggactcccta cccacaactc cattagtccc cgcacttcac ccatgaccac a <210> <211> <212> <213> 101 933 DNA Aspergillus niger <400> 101 atgggtggtc gttaatggcg accaaccaat gttgccgtcg aagggat ccc gttgagtaca acctacactg agtcaggctg cagaccggtg tggtacccgg gttgccattg accggccaga gagtggattg accgtcacct gatgcgacca agcgactctg gagatgtcgc ttgtctctgg tcttcaagaa cagctcccca gacccctcca gctccaactg cggtgaccgg cat ctgcctg ttgacttcac attacgccta tggagtccta aggtqtccaa tggaagactt tcactggtgc tcatcgagat aggtgaccat cat tctcagc gatgttccaa gaagttcact gcgtggcctc ggcagttgct gtccqgtgcc caccttcact ggttggtatc cgtgaccgac cgacttcagc cacctcgact ggagctgtcq cgaggaaaat tgttgccaag tgaggagaat cacctacgag aggcactttg cacacagtca gctgcaattg gaggcccgcc agacctgcat gtgctggtgg gtccctgagc gacggtgata ggagaggcct ggcatcgaca accggtattg tccagctcca ggttcgctcg gcggcgggtg ggccaggttg taa ct gtqacatc cctcttcacc ctactqccat tcaaggcccg caaccaagaa agcctccctc ccaccggcaa cctatggaaa cgttcgatgc tctcggcagg ccattattga gcctcggtgg tcaacctggt gtgagagtgt tcactgacgt ctcacaaagt cagcttcact tttcgcaagc cggcagcagc ccagaccaac tgctgcagcg ctctggaggc cgccattctt ctggtatgag cgatgagatt gaacaagagc acagaacgct ggactttggc tggacttacc taccatcgac 120 180 240 300 360 420 480 540 600 660 '720 780 840 900 933 <210> <211> <212> <213> 102 2046 DNA Aspergillus niger 137/I282 <400> 102 atgcqctgct cccttcgcac tcccgaccgt ccttctgtcg ctctacattg gagtaccatg ggtgacggta gttgccacgc tacgtctcca gcgcagtgga tatctccgtc acccaatggg caagaactct aagccatact tacgaa'atga aactcgacga ggctccggtg ctcaaaggcg tcggcgaccc agcacctgga taccgcttca aagcagctgg gtctacgacc taccagccca gagacgagag gaggttctcg ccgagtttct acctacggca accgtcctaa ctattcacac ccctcatctc acactgcgaa tgattgcctc gqcagaaagg ccaacacaga cctccttctc act ctgacat ctgcagtgga ccgccaacaa acctcacaaa ctgcctggtc acggacacqg ctct ct acgc act ctct tgg cccgggaaga tcatgtccgt tcaagcaatt gcaccagcga tcaggtcccc qcatccgctc cggacgtctt gcaattcqtc ccagcacggc gctggtcacc aagcctcagg tgaacagcag cgccggatgg acgccagcga ccacagaatg gcaaaaccag ccttctaggc catgggcatt caagagcagc cgtgttcatg tggcagtaat cccggatgta ctaccgcgta agactccgtt catgaaggca tacacccacc tcctgatggc cgtaccgacc catccgt ccc atctccgaaa cacctacaac agacttcgag ccctcagtac gggcttctac ggcgtggtct ggggtacaag ccctcaggtc catcgtgacg ggactttgtc ctgcggcgag cggatggatc ctactccatc caagaaagtg gatcgggctg ggacaatctg cacqtacaat ctggcggcca gataacatgg ccctcaactg atgaaccgca gaacgcccac gaatggatca cggaccaacg gttatctctc aacatctgga actgccgcca gaatggatcg ttcctcggcc aatggctctg tggtcagcag gcccatcgtc acaggcaccg ctggacaaga acgaccgcgg cccgacggca cagctctaca tcgcaccagg ttgaacacaa agcgatgacg tggctcgtct gtgcgggcca accgaggatg gtgtatcggg cgggtgctgg ccccagttct tacgatgtgt tcccggccct tgaaagcaca ttcctacctc ttgctcctgg tcctctccaa ccttcaccag gctccgatct ccaacggccg tccttgatct actcctccct ccttctcttc gcacgggctg acttccgtca acggtaaacg cagaaaccat atgtgcgcgt acggcaccat gactctacgt agcaagtagt gctgggacag agcgcqtcgc ccggaggcqa aaaccacagg tcqqcgtcgq ccqccaacgg gagccctgaa tttggggagc acctcgagac ctcccgatgg gcacgatccg tggaggctgt cgctcacatg ctctagcacc cacatccgag ccccgtctac cgagcgcaat ccaggaattg cctggcagcc tcagaccggc catggagagc ggaccgcaac ggagacgacg gatcatctcc cat cgt ctac taccacagcc ggaagtcgcc cgcctacacc caacacgacc ctacgaaaag tgactqggac cat cacacag cttgcaactc actgagcgct attctggttc gagctactcg cagcggttc cgacactgca gcgaaagaca agagctcatc gccggatggg 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 138/282 acagatctcc gcgtgttgac gagcagcggt gctaatgatg cgcatgcggt ctggtcgcag gatggacgga ttatgtggtc taccgqcatg tatgggttcc ggtttgagtq tgcgctgtat ggtgatacgt tccagccgta tgggcaggtt atgattatgg atgcggatgg gqgaaataag aagttgatga ccaactcgat gtgggaagat tcgatgccgt tgttcttgcc gagggaggta ctttag 1860 1920 1980 2040 2046 <210> <211> <212> <213> 103 1875 DNA Aspergillus niger <400> 103 atgcctccgg ccacatcctg gctattattc agtcaaacac gtataccatc aaccgaactg gtacctgtca ggatccggag ccagaatcac ccaagagggg aaagcgtggt gatactcgat ttcccagttg ggggaggaga gcggctatgc gattattacg tttttcgagt cccgaagatc gctgtgtctc ttggtcgtgc gctgagctcg atgcaaaatc ccaagggaaa aattatatgg ttgatgatga catgctttgg atggtgaagg cagatgcgcg tgagcatggt caagtgcaga tcaacaacac tact gcagt C gggcaaggta gaacaaacgt agctgctata agcctcatcg ccggcaactg actgctacac tcaagtctcg cttctggaaa aagctctcta agcaaggtaa gcctggctac agccattcga taatttccac gtcctttaaa tgatcacgaa gtcaaaaatt at atg99t ggt ctttagatac ttcagcgagC aacacctaat agaggcagag cgaagctttt tgacgccgag ctggggcttt cataaaccgt gcttaccaat agctggccca ttatgagcag taggggccca tgtgcctttg cggctcttca cagcctggta ttcctccttt aaaaataoaa tgggaagatq tgcgctcgct gccttggcgg gccattcttc gggaaagcta ggaaagtatt ttttcctgct ggtctacttg gagcggctac aggataaggc tcctatggga gctgtcatag ttacaagatt tcagcgtgtc attttgacca gagataataa aaattattcg ttcgctgact tggcagtatt cccttgcatt gcottgaaca ttactcctac tgtcgcttcc ttatcaaact tgaatccagg tccagaccat tcgatgttgt tccctgaccc ggagttctga tttcgacagc tgcacaaccg caatcctggg acggagtctg cggatgcagc cgtttgcgct atcttacatc cctatagtga atttggtggc tgaagtatga accatctagg gqtcgcgttt acagcttcaa caagcaactc aatgaattgg tcCtqccaag tggtcctggt cgtcgactcc tagctttgat cgcgacgagg aggagtcttc tccgaacact ttggaaaaaa ttccacgttt caacgctgat attca a ta aa cggcggagat gagccctatt tgtgaagtca taggctatta agccaaacaa 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 139 /282 tggccagtac gatcaggagg aaggaggatt ttctgggccg gatggtatgc gggaatactt cctgagtcaa ttgtgtacag actgtttgcc atgtcgccag ctgctaggcg cgcctccatg ccgggaggaa tccggagcta aggttcgcat gtatccaagg atgatccagt tcgttctaga cgaaagcgat aggtagagga gtgacacaga cgtga cgattcctcg tatcctatgt ctggaatatg gtcgtgtgtc gcccttcgca aacgccgcta gcagaactct acgccagtat gcttcccttt attqatgtcc tccacacaat acagatggtc ctccggqgac aaactggaga ggcaatacat cggaatgctc gtcggacatt ttccagaccg cgtcttgccg gccttgcatt acaaagtacc caggcctcga aaagtaaggc cgcgacctga cgcacccatt at acgat gg c gcacactgag gagagttacc gatatgagag cgctgagcga tggcgagagt cggaactgcc ggttggagat gtggcgctat gctgtttatc gcgtggattt tggcccatcc tqaccccgga aagtcaggtc gttccgccat 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1875 <210> <211> <212> <213> 104 1665 DNA Aspergillus niger <400> 104 atgttgagta gagccggaag aaagagcctg cttccccccg gcgcctctgg gaagaat tag agttggaaca tacgatgtcc ctatggcatt cgtgtcagtc ttccaacagc cat ctcgaca tacattactt tttcgcgatc cactcaggga cccatcacct gtctgctgct gcatcactgt gaatttgcga cctcaaccag ccatctggct gtccttgttc atgaagtcaa caacaaatgg tcgcgcaaac tctgggctga agaatgacaa cgcttggcat ggccatacaa aggccctcgc agaatatctc act accacac tgggggtctt gctcaagtcc aactacgccg cttcttttgg caatggcggt cat tgca tca tcttctattc cactttgaca ctggtttttc aagttacgga aatcgcagag tqtgaacggc taacgtaagg ctgcgaagcg tgaaatttgc cttcaatcgc ctgggtctag aagttgcatg ggtgtccgat tttttcgaag ccgggtqgct gactccaaga cttgaccagc gctaatggga gagttcccac ggccattatg gggactgcag ttgatqqata ctcgcccctt gctttgaaag ggaggccttg gggtggtacg cgaccgctca agaatqtgac cttattcggg cccgcaaaga cgt cgct cat ccacagtcct caactcaagt ctgcattcgc actacaagcc gtccaggcat aagacggtgc tggtgatcca cttcattcaa aacgcgattc cactagaatg acatcgccca atttcctccc tatttctttc ctatgtacac tcccagcaat ggggctcctt caatccttgg cggcttctca ggctcacgct aaacgatgat ctttcqgttc acagtatttq agaagaggct ctcgcgaggc cggcttgcct gggagatggc tcctaagaac 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 140/282 gacccattcc cttqqggtac acctttgata gtaaaagtac aaagccagcc ccactcctta act cgcgt ct atcttcatgc gaattccagt ccaaagccgc gttttgaacg gaggaccacg ctgccaagca cagtcaattt tcgtccacgg acatgatgta ttgcagttcc cgcccgacgg tccaagccgg gggcgacatt cggttggacc agtgctatgt gatccgcgac aggggttcag catqctcgga cacatcgtct cggcttcctg cggagatcgt gtattcccgt gatcagcggc gcatgaggtc caacaaagat taaggatacg tctaagtccc ggtaaaggat cattcttgga tatttgacgc tcgagtgccg gatgcaattg gattacgcct atcaccgaat atgacccgcc ccctcctacc atccctactg tggcat at ca ggcacgtgta tggtatgtcg gggqatgagt aggagtccgt tggctacaca gctacctcct gcaattgqgt ttgccgaCac agctgggcaa agcctgtcgc gcctcttggc agaatatCCC ccccggaggt tggatgatag tqt a g ccttgccgct gttcataaaa cgacagtgqt cgggggcgaa gggataCtCC ct acagctt c ggcgtatgag tgttgatqac tcctattatg ttgggagacc cgcgggtgtt 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1665 </210> z2 11> <212> <213> 105 1737 DNA Aspergillus niger <400> 105 atgaccaggt cttagcatc ggcttttgtc aagttcgtag caagttccga ttcctcgact gtagatcaca aagcccctgc acctatcccc gactgcaaga tgggagccaa ctcggcgccg tttatcctcg gtctacgctc ttcaattqct cttccccgca cgctggcacc aagatgcctc ccgcaatcga tccagaagct tcaaccgatt tattcaccgc ccttcgatgg acgtcctgat cccgcacagt gatccatcgc acgaaggcgg tccccggcgt tccccttgtc gcagggctgc ttgccccttc aattgcagcc gcagatcctc caaggttgag gttcaagtcg cgactacatg cctgcagacc tggtctcgtc gcaccaggac ccactacgac cggtctcatg cgtcctggcc caaattcctt catgggcctc tggcgaaaag gattctctca gttcctgacg cqccaagtca aaggatccct ctctttcccc ttcaccctca gtcgtgccca ggcgaatggc tccgttgttg ttcggattcg gagaagaaat gaagttctag ggcagcatcg ctttcqgaga at ggttt ct t atcgtctctc acgacgaaaa tcacccactc atggcacaga tcaacgaccc tctggggccg aagacctact acgaagaatc acggaccgga acgacaacaa acgttgtgct gcacaccgac tccagctctc cagggcggtt gttcgcccca ctacgcccgc tgactcgctc tgccgactgg cggtgccagc ctcccaaaag ccacggcttc cagcttcgaa caacggcgtc cactctggcc 141 /282 gtaccaggcg gccacagctc cgtgccccct ccacacacgg gaatcggcat catcgccgag at cat ctatg acccgcaaga gcctccgccc ggcgacaagt gtcaaatcca caccaaaccc aaatataacc aaccacctca gacatcgaca tctgtcccta acggatacga gcgggtaaag gaggcgatga gtcatttctg agctagaacg tgctcgaatg tccaatcaag tccgcttcat acgctct ccc cagacgatat tctccctcac ccctt acta c ccgacgccgt gtctcgaggg oattctactq cgctgaatat tgctgtatta ctgcgtcggc ccaggacctc ccaagtccgc cgactacatc cctccaaacc cgagaaaatc caagaaccgC ggccttCcg cctcagcggc ctgggcccgt cagaaaggtc qgctttqtcq tcatactgtt cgatcttatt agctgctgat ttcgtccccg cact ccccct tccctagcag tcccaagcag aacgccctcg gctgtggaga gaaagcgaca gccctcagtc ttctcggqcg gtcgtgagcg aggaatattt gatgagagga cgctctttcg gatgaacttg tcctagacac cgcaagtcga agaaactggc cggacatcat tcaactaccg tcatctctcc ccgttgaccc ccgccccggt tcactcgctc gcgacatcat acagqtggag tcgatattga atggacggac ctcacgacgt tcaccacccg accgtggctc ctcctcgcgc caacggcggc catcgctctg catcgtcaag ctccctcaac cagcccaacg ggtcttcgaa gaccgggaat tccgtcgagg tattcatctt cgattcatct gctgtga 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1737 <210> <211> <212> <213> 106 1371 DNA Aspergillus niger <400> 106 atgaagagca atccacgagc gaccggtcc cttggctaca gacaccggca gattacggct tatatccaqt ttctccaatg gagggggtc g g t gaat aca tacagtctat aacaccgcca ccactcttct gcgatgaacc gtcggaagcg cgatgaacct gcagcgatct cttacaactc atgtcgacgg tgactttgac tcggtatcgg ccaacttccc ggctcgatga agtactacgg ttccttggcc cgctactctt atcgaCggcc caca ctcggc ctgggtcaat aagcgcttct cagtgaagcc gaactttcaa atacgCCagC cgaagccctc c ctcga cga a cagcctgcag tgggctgccc cagttcaact tcggccgacc actcccggcc ggggccaact tccacctaca acaggcqaCt tttgccgtcg aatgaagcca gtcgatcaag ggaaaaggca accctgccta agtccgccta ttgaacgtcg tcgttaacct aggaagtCag cgtccgtctg ccttcgtgaa atgtCaacga catatgacgg gccaggccac gcgcgatCaa ccattctgtt tcgtctccat ttccctct ct tcagatcgcc qgctacgaat tgtgacgttg cccctgtacc cgatgagttt tactctaaag CgaCtccgag cgtcqgtggt ctggccggcC cggcggagtc cgaagaCatg 1421I282 I00 00 tacgtcgagt tcggtcaaca ctgacctaca ctgagcgagt ctgttcgact agttccgaca gccctgctgg gagatct ccc acCggatcgg tccacggcct attgtctcgc tcgcggtcaa acagcgccac tcccgacctc acgggtacgg t tqga tcct t tgaccgacat gcgatacctt tggCCaaggc atgcCgtgcc cgagcgaCaa tggtggcggg cctgacggcc gcaattcccc cgccgcagcc agtgatcgag caacatgagc gaacgtttgt cct gCgcagc caacttcaac caaggcgacg gtcggacaag agtcttggtc gtgcaCCttg atccccgcc agcatctaCg tgcgacgtca gttgacatca acgtttggcc gcatacgtcg cccggcgagg ggggCgaCgg gagagttcgg ggtgttttct aqaagaacgg tgctggacag aggccgtcgg agqacgaaga gcgagatgat tcgcagtgat tctacgatct accacgtcct cgaccggcgc ctacagtgcC tggttctgta caactccgtc cggcacggcc tgcccaatac cttcaccttc cctcgaggcc cgaaaat gag cggaaacaac ggagatCggC ggcagccaca gcgcagccag a 780 840 900 960 1020 1080 1140 1200 1260 1320 1371 <210> <211> <212> <213> 107 1995 DNA Aspergillus niger <400> 107 atgttggtcc acatccatca ggtgcgcgCg ttggacaagg cagtactggt gcagtgagaq aacaagggct gaattccaCg cacgtccCc caggtcgtga gccaagtctg gaCCtCcgCg ccagacgcta tttgccaagt gtcagcttgC agcatgtcct ttgagagcqa gctatgactt cggcagacga aatggcttgt ggctcgCgtt agcaCgagag aaca cat cca agaggaccaa ctgcCaagg gctgcggtta agacggcgac ccgacctcga cctggctctg gcacgagaaa tgcggtcctg cctgatggaa ggtgcaCgac cgcctctggt cgacgcctac cgaccgaagt gaagcacatc caaagtcaag tccgcagcca caacatcacc cccgaacaac cctcttctat gccattgcgg cgtcacaagc cctatgcgca gtatcggacc atcttttcgc atccatccgt gcccatgaag gctaagatca gactacatta cgtgcttccc ctccccaaca ccctcgtgta agcctgggtc aaggagtatg ccttgtccga ccgcatccga ttggccttgC ccaagtcttc catccgagga cgcgggtqgt ccgagaggct gggttggatg cccctgqagt aactagctCa aggccaagtt tcaaggcctt tgtacgagca cgccgtgggt cggttccttc tgccattCCg ctqggtgaag ccagaacaac caaatacggc gqctgttgag gcactccgac gttcatgacq cgaccaataC gaagctCacc ctcttccaag cctgcctgaa gtatcagatc gggtgactac tccccagggt ctacagctcc acctatccca tcccagccct gattgatggC gccaattact 143/282 00 00 ctgaacacgg caggtgaccc a at ctqtt Ca ggcgagaccg tacaaaggaa ggccaatccg aagCtcggtC ttcgcCggcg cagtacccct cagaccgtca ttcagcactt gtgqagcaat gatgttaaca gcgaatggag agtttggCgt atcggcaagg aacgat at ca ggatgggatc ctctctttgc gtgaatccga tctaccaggt acaccttcct gcgatga ccc agctccagtg aagccgacct tacagggaca acggtgacga ccaactgccc acgacagcga ctggtggctt acttccagtc cgaccaaggg cgcatttccg cgcctttgtt gccccgtggg ctaatggtac ccgctagtgg ct tag cattgacatt tgacgaccag cgacgctctc gtcgatcgac cggcgtctat ccccgtcagc Ctccatcctc gaacggctgt ctaCgtca CC gagcgtcatg ctcgaattac tgcgaacctg tctctacaat cgcttatatg cgcgtcggtt attcgtgaat taatgctggg tttgggtacg gacatggcct Ct ctacgaa C gatggCtcct cccgtatacc aagcccacta tacaccaagc ttcgcqtctg ctcgcccag tccgttggag cacgttaacc ttcccccaac tcqtatccgt aggcttggtc gatggatacg cttactttgC cccgtgcttt tgtggaactt cctaactacc aCt ccctgct cagtcgaggt actgcaccta ccgacacccg acgtaatcag gccaatgcaa gcgactacgg agggcaagat gtaccatgct ttggcggaac Cggcatatca attactcgga gtgcttatcc attatcattg tcaacgaqqa atgcttatcc atgggtttag cattgatgaa ctaccctcag cgacacaaCC cagcgcctac CCCCggCggC cgcctcctac tgagttcatg cgtcgcgtct cttcaacccc gtacggCtac cgcaagtaaC gtttgCtgCt gtttgaggtc ggatgtctcg gtatggatcg acgcttcgct gcaagtgctg tgctattgag ggagctgttc 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 2740 1800 1860 1920 1980 1995 <210> 108 <211> 1563 <212> DNA <213> Aspergillus niger <400> 108 atgCgggtta CCaCggCaat tgCttCatta aatCCtCatC gtCgggCtgt tCCqCCCCCt gtgCCCgttg agcgccgaac CaCCgaCttt CtggtCaatg gCaCaagCat CCCCgaagtC CttCtCCCCa ataCgCCCaC tggCaattCt aatCCagagg CCagcgatga gatCaCCatC CtagaCggCC tgCttCaaga gaacggccca gttcctaatc catactcatg gaCCaaCCtC ctactggtcg ctCtcgcatc ga gtat t tga gatttcgacg agcctattct tggctcaacg ttcctctggc accaatgtgg gctcggccac gcagcgtagc ctaacaagac tcggcgagtc tctggttctt gCggCCCCgg agcctggcac tttacatcga cagtctccaa gtctcgctcc tgCaagattc ctacgccggc cccctcgcaa atgtagCtcc ttaCaagccc ccaacccgcc 120 180 240 300 360 420 480 144 /282 00 00 ggcacaggct ttcaacagct atcaccggtg gaggaggata agcgactcgg ttccaqctaa aacgccttcc gaaatcaccg ccctgcttca tt cccctccc ct gcacgt cc gacggcagcg act a tcat cg atccagaaca ttcgtccctt aaccttgatg agctcggtgt cagttqgagt tga tctccccggg ggttcaagca aaagctacgc caacctactt tcatgatgta act cca cttt tcgacaaagc aagactgcca attactacca tcqcctccgg ctccaacgga accccagctc gccacggctg tgacctggaa accattatgg ctggcgctgg atttgtctgg tcctgctcgq cccctcgacc cttcgtcgac gqgcatgtac caacttgaag ctcccccgcc cctctcctac cat cacctac agtctgggac cctgatcgac cccaaacaac ctactccgtg ctggggtccc gctcgattac cggtaagcaa tctggctqag atacctgggt tcatgaaatc taggattaqt gtaaataacg accttcgacc gtcccctaca ggtatccaga gtccgccatc atcaacgcca ccacccccca gaagtcgtca ttctgcccct tacttcaacc tqctcggaga ctacccagcg ctcctcttct gqgttccagc ctgtactggg acagcgcata ccgcagtatg agtctttcgg aggaaqacgt tgcacggccg ttgccgatgc tcaacgacc tgaaccacta aagccgacaa gtccctt ccc tgqccgccta acctctggga gctccgacgt ccgtcatctt tcatcgaacg tgaacggctc gtcctcccgt gcgatgagcc ccgagcgcgg ttcctggtgc cgaaggggaa ggctgcccaq caaggtctac cat gct gaac gtccatcaac caacaacatc gtgcggctac caccgcccct cgacatcaac cgtgctcggc ccagaagatc cgcgaacggc cactaacaac gctcgccaca ggaaccgctc tqacccgtat gttgactttc qgcttaccgc ctatacctct 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1563 <210> 109 <211> 1656 <212> DNA <213> Aspergilius niger <400> 109 atgcgtgqct ctcggttggt gctcttgttg gagaatgaat ggtcatctac gataagaagg tcgataaaaa ccccaaacaa tgtcactatc tgtgagacaa cacctggggt caaatcatac catactttct tttggttttt cgagtcacgc tggctgaatg gtggccctgg aagcgattcc tgtcacatca caccagagta cgaatcaatc cccctggctq caqttaccaa aggtataaag tccqgatatg cgtgaccccg ttgattgggc atcaatcagt cacttagttg aagcgtccac aaccaggaac tcgatctttc aaaatgatcc tttttgaaga actcctggaa tgctatqccc tggcgtcaaa cgaaggaatt gccagaqtcg agtgactctg gttgggtccg cgaggtcacc 145 /282 aatcttcttt gggtccttga cgatacccag tgggaggtgc aaggagttca catttctacg tttaactccc gcagactttg tatatgaagt ttgaccaata agggacaatg cacccctaca gtcatggatg gcattccagc ctccaactcc ttcggcggtc gcgggataca aacttttcgt gcagcgttgc cagatttggc gtgccactgt tcttgtctca atccatttac ttattgatgc ttcagggctt acctgtggac agcaaaattc tcgggattat ccgttaataa tcgccaacac ggacctcgct tcgaagggcc atgacccgac ctatcggcgt agaccggcga ccgtacqcgt aggccatctc cacccatgac tcacccgcgt agctgttcaa ccgaata tag ccacggcgtc gcccctcggt tggagccgtc cactatcatc cctcagtggc agagagttac gaagatcgct caacggcatc tacatatgga gatgccaaat ttctgattat ttactaccag cccgccgtcc ggacattaac ctttgtatgg gtcgttgatc act cgcagtt agtagatggg atatcaggct ccgtacttta caccaacggg gagtaccgtc gtggggttct gagaacgcct gacacgaccg ctgtcgcagc ggaggacact agcqgggaaq attgatgccg atcaaagctg ggatgccagg gctatatgta tttggcggcc tactttgttg tacaccgaqt ccqaatttca tacggcgatq aactaccccc gtcgaatacg gggcacgagg tttggatggg acatcgcaqg aattag cttacagtga cctttgctqg atatcgctgc tagattccga atggaccagc tcaatggcgt cgattcaggc tcaatgacac atcaggttgc cagaagcagc gtggcgtgta actacctcaa ccagcggcga ttgaggacct ccgactatat atgcagctca gtgagactcg ttccatacta atattgcagc ctacacacac aaccgaggcc aqttcagggt acgcgcaacc agtcaagtcc gttcttcaat ccaactgaat agactactac agtgtacaac ttcgtgtaaa caatatqtgc tgatattcgg gaaagactca agtatat tat cgaagagatc ctgtaactgg gttccgtgca cgagtatggc tcaaccgatc gggtacaact ggagtcgttc 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1656 <210> 110 <211> 1872 <212> DNA <213> Aspergillus niger <400> 110 atgccttttc ccttttcgtc cgctcttctc ggctatatct acctccctag tcgcaggaca gtattaccct ccgacgcctg tcggagatat tccctggtgc gaggatctcc tataagcaac accccctcca cccccagcta ctccggctac atccacctcc ctctccattc caggaatcag catctcgcaa ccatacccta tttccttccc gccatcacca caacaatgat acatccccac taactacgag cactactctc aggatctcac cgttattcat ccctcggcat ctgcaccacc ccccacacac ccttaccaat tcaatacctt tttctggtac tcaccatctg gatgaacqgc 120 180 240 300 360 146 /282 gggcccggcg acggactcga tatattgagc gatttgaatg aatgggacg ttctctgaat tggacggaqt aatgagagga ggcattatca tataacaata agttggagca ct cggagat c agcctgtata gcagctctcg gggtcccgg ggcgat tat c tccggtgtca ggggaagatg tat gccgaag ttctcgttca gcgtatgaga ctggagcaga gaagtgccgg gatgagcaga gatgatattg ttgggacatt gatcctccat attccacggc agccggtgca agacgttttt ttaatggggg a tgttt ctt c cat atggggg ttgagagtgg atgggtgtgt cgtatgggat agcctggcgg ccctcat cat cgaatacctc tgccttactt tqaactatac cgcgaaatga aggtgqctat tcagcctgct tgcagacgaa cgcgtgtctt tttttaatcg atcagagcta agagccctga gggaacgggt agg ct ga aa g ga gattgggcta ctataatccc gacgggattt ggtgqggacg aagggcgctt tgttgacggg acggtatgga ggaggtaagc ggatttactc cgagggaatc gtgcagggat ctgcgaggag cgggcgagga cgtcgggttc catgtcgtca tccccgcqga ggtatatggg ggtggagtac gtcatcctac tcaggcgggc cgctcagttt tgggacggag gccgacgtgc gctgagtggg ctcgttcagc tttcaagaga tggtcgtgga agttatgatg ttgccgagtc tgggttgcgt aatggtggtg ccggcataca accgggaaga gtqcaggtcc aatcgcacgc atgatcatcg gcgtcggact tact acga ca ttgaatcgcc gagcagtgg atgatcgggg gaccgggact gaggatgcgg gttgqqggtc catgaggtgc aattgggata ggaccgtcgt tatttgttgg gatgcggtgg ggtgttggtg acgggccatg atgagtacgt tgttgaggaa aggatgtgca tgcaggtttg gtgatgacag cggcqctctt agatccattt cttcgttccc tctacgaccq agtgtcgcga actgttcgcg tagcqcattt catgggtgca ggaacagttt atattggata atgcttgtcc agaagttccg tagtaaggca cattttatca ttgcgacggg caacgtggca cgatggattc tgagggattg atcaqctggc tactgtgaat cgatatgttg t ggga cgt ta tgggacggtq gttgggtgaa ggtgagtata tcaggagatg ggatacgctg tgagcaggcg ggctatggat tgctggcgag ggagatcaag cacgccggat aaaggcactt cqcct cqacg cttgcttgac gtggcgcggc tgctgctggg gtatgggaac gcccgaaacg aggcatttct tatcaaaaac gacttgtacg ggttgttgtt acaggtccct 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1872 <210> 111 <211> 1320 <212> DNA <213> Aspergillus niger <400> Ill 147 /282 atgagaacat ctactctttt gctcctctgg agcactgcag gagcaqcttt ggcttctccg tacccgcttc ggcaaacacg gctgcaatgg cacattcgg caacgcggaa atggcttcqt ccgctgttct tact aca a tc tacattgctg acccatcctt tcccaacctt ctgcccgccc cqcgttctgg gcggctgaag ggcgctaaaa accgagacca aacctcagtc ggatccgact aacccgctcg gataggatgg ccgactcgca tcgtggacga tgtctctacg gcgaagagaa agaaqtt cat ttgctgggga ctcaaatcga gatactacgg cgat cat ctc tccgccaatc tgaccat cat ctggcgctga cggagaatgg aggccqggct ttgatgccat tcgggtttgt gagaatacat acatgtcata ctgggggctc acgttgacga agtaqtcttc ggccatactc tcccgaaact ggcggaatgg gga cat tacc tcctaatctt gacggaacga tgattatcac caaatcgcct ttcaattatt tggtgcgcac cgatgactgt ctacacgccc actgggcagc gatggagttt tgcaacccaa ctccattccg cactaagctc tttcccgggt tgaaacgggc gccgcggatc tcggcgctga gcagcttttc atgaccgaag gagcatcagg cccaagctgt atgcacgata gqcgagatga ttccgcaccc gcacgcttcg caagattcgg tccggcactq aaggacgggc caagccatcg gatatgacgg gccgatgcag gcggaagtct aactaccccg gaaatggacc gtcttctcta acgaggtccc acgctcattc tagctgaacc gcgacaagct acttctacgc cccataaagg tcctgcagca gctccgaatg acatctctct agcctaaagt ccaattatlct tcagtatcct ctgttgaatt cgcggtacaa cttttattgc cgctcacaaa atqaacttgg ctgcct ttqc cctacgtaca tcgaacacat gaatacacag tgacccagtc tcgtctcttg gcgcctccgc agagcaggcg tctcgtcaag catgacctcc gctgcacgac cgaatacttc tcgcaqcttc ttttcccctg cgaggccttc ccattggtat gaaggagcag ccgtaacgcc ctgggccctc ccccaacqct atccgaaggc cggcatcaag qgctcggttc 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 tccgagttgg ctatcgcatt tgttgtcgag caggctgggt gggataatac atggcggtag <210> 112 <211> 1581 <212>~ DNA <213> Aspergillus niger <400> 112 atgcgttcct tctccgttgt cqctgccgcg tcactggcgc cagqctgctc gcccccgtct tgtgcccaag cctatctctc qctgcgacta cgggtgaggc ttattttgag cagctgctgg ggaacgtttt cccaqcggta ctggtggagt actgaatact gtggtcctct ttaaccctgg agaggtctct gccgatggct tctcttgqgc gtctctggcc ggccagcttc gagtaagtcg accatcacaa cccggagaag gggqtqgacc tgggtcaccg atgaggggta tctcaccaac 120 180 240 300 148 /282 gat act ctca cqctactggg acactggatc gataataqca agcggtgcct gccaccagtg caaggtatgg attgggaaga gctgttgagc gacaacgact gtcgaagccg gccaactacg tactggaccj ttcaccgaca gagcctttct ctcgtcagcg tacacgtacg tgggatatga cgcgactccg gaacccgtgc tatgcgaatg ctggtgtcta gcgactcttc agtccattct gccgcagcaa tgacggcttg cgcctgtgga cacagaactg atggaactgc attacgatga ttgtcacagg gcgcggcagt caaactggtt acgaatggag cctccgtggg tctggtggca cctcctactg gcagcgcgaa cccgcaacac gtgtgtcgag agattattcc agggtgtgag tgcqcaggag gccttatgag ggacatgacc tgcgcagaat gaccgagtct ggctatctat cagcaaggat caaggaacag ctttgccgct a tactct t cc gacccccggc caattcaacc cgtcgcctgt taaccctqtc ggacggtgcc gcaacgccaa gggtaaaaac gacgcggttg cactttccgq gggcgggttc atccagggtg gtgctcaatg tacttcgccg gctccctggg atcgcqcctg gacttttggc gtgtctctgg caggagctca gtcctgccca ttcttccagt cccgagggcg at act cccta ttcgacagct gaccgccaat cccgagggaa tgcccgctct tccgctacgg atctggacga cccggtggtc cattgctcgg ccgtcattct ccgaaacact agacggtaaa tcatggtcgg gaacgttctg aatacttcta tagccgagta aagaattgtt acggaccgta tctqtgatgc tcggacttga actactgcgc ataatgcctc gggaatggtt cctccactat acttccccga tgaacagctg acgggcaata cgct ggt tag acttgtatat cattgaacac tcagtatctc gctgcagttc tggctcatac ggcttaccat ccccattcag tgtcgacaaa tggtctggga cctctggcaa tgtcgagggt aaaggccctg aagctacggc gagccccatc cctctgcaac tgtgccccgg agttaacggc gacgggtgga tgacccctgg cacggcgaac ggaggattac 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1581 gaaggtggtt gataatgagg tgaagcagat taaggagtgg gtggaggagt attatgcttg a <210> 113 <211> 1275 <212> DNA <213> Aspergillus niger <400> 113 atgcagctcc tccagtccct cattgttgcc gtttgcttca gctacggcgt cctctcctta ccccatggcc cgtcaaacca gcacaaagca cgttccttca aggttgaacg ggtccgtcgt ggaaccggtg ctctgcatgg gcccgctgct ctccgcaaag cataccggaa gtacggaata gctcccagca gtttcaacat cgatctggca gactttaaac ccattacgac aacccatgct 120 180 240 149 /282 gctgctggqa gcgagattgc agagcctqat cagactggcg ctgtcagtgc tacttccgtc gagaacgatg t t tga cact g gqacacacgg ttcgatgtct aacattggcg tcgttcatcg accatcaaac cccgtcatga gacaaagaca tggcagttct ttgaacacct actgcct act tacccctgca acgatccccg gccttgtgct attttcctga tctcccaaga ccgagttcgt gttcttctga agtacaaccc cgtatggtga gcgccattgt aggacacgaa cggaggcgca ccgcctcgct agtaccagqg ccactcccaa cgatcgcgga atgcgcaagt acaccactct gtaacctgat ttggcggcat aggccttttt acta g ttcgcctgtt cttttgggtg ttcgaactcc cgactcgtac caaggagcaa ctccaacggc agacacgttc caaggctgac caacattgcc gtactccgtg caccggtacc tcccaactcg tcccagcttc caatttctcc tcaatccaac cgttgtcttc cttattggcg ttcgatacga tcgaccttca gcctctggcc gccttcggtg ctggtcgqgt ttcgccaatg ggagtgggcg aacatcagcg gcagacggag tcccttatgc gtctacgtga tcgcttqtcc aaqgttggca ggaaacacct gacatgcgcg gccagaagat atctcaatga agaagatgga ccgtcggaac tccccgacca tgggcttttc tcgcaccaag agtacgagtt tggactcatc agctgaagga tgctggatga gcaqtgccgg tcggcgagtc ccaacaccac cqctgcagat gcccctcqct cgtcatgaca aaccttgacq cggatacacc ggataccgtc ggtatcccag ctccatcaac tctggacgag cggcacgatc gaacggatac cattggaagc agacgtggtt tggttacatc gagcctggcc caccggacag tctgggcgat tggtgttgcc 360 420 480 540 600 660 720 780 840 900 9 1020 1080 1140 1200 1260 1275 <210> 114 <211> 1647 <212> DNA <213> Aspergillus niger <400> 114 atgcgcattg actccqcggc gctacatctg ttacaattac ccttggtcca agactccaat aaacccctaa ttagctctcc gttgcttcaa agggcccggc agctttacaa gattgcggag cgcgtcattg qcaqtaaagg tcaccttggc gacctcggtg attattatac tgtcgtcaat ttcgagtctc gccttgtcct tggtcacgat actcccccaa cgaggaataa ggagccggta gggtgtgagg cctcggacta ctcgtccaac gtcccagtcc tcacagtggc gagcaggtca ctgqgagaag acgctcqact cagtccttcc gttcccaagt tatggctccc ttgaaaggcq tcctgggcca agaaaccaaa aggcggagaa acqagtataa acatatactc ctgccgtgag cagctacacc tggttgctgt ccgttgcatt ggtcggtgct tqcaggtqat tctgttggac ccaccccact cacccttacc cggtaatgtc aatgggtctc atccaacctc tatcagtcgg 120 180 240 300 360 420 480 540 150 /282 ggaagctgtc cgttcgggac caagtctcaa ttagctggta aagcgggagc tgttgctgcc gtcatctaca catgttgcta aaaggcgaga accaatatca cacagtgaca cttttggagc tggtgggccg ccggaagaga tttgcgtacc acaacgagcg cctttggtat aggtggacgc tcgcgcagac gcgtggccga ttgccacatt ccgaggagga accgcaagat aagtttacaa gggtgacctz Ctcagacgac ta tcgcctac cacggatggt gggcccgggt gctcacccag aggccttctc ccgcttgttc tgccactaat ttacgaagat tgccttcatt gactgtcgag ccatcagatc gctcgttgcc cgatgaaccc attacttcgc tggaacagct Iagctaa agcggaactc taggaaaccc qatgctgccc gttgatgcga gacccgaaca atcaatgacg ttccgtgtca ggatctgact atggactacg gctgtgaacc catgggttca cggcatggta gaagcggaca tqcgatacgg cactccattg cagtcctgga tagtagaqac at t gtgt aat acgggtccgg acaactgcgt attacgtgtc acatgctcgg ccgaggqatc act acacgta tcccgqgtgq tgtttggtgg tggccaatgt cgacttacgc aacccccgat qaagttgaat cat ccaca cc gctgggtggc tactct ga cc gcgatttgct cgttctcaca Ctcgccgaac tgaggagctt cattccgttt tggcattgcc ggttgctggc gaacttgact caagtccttt ggaaccgaag gagcgtcctg 3tccatacga 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1647 cgtgatctgt acaccgactt gacggacgca acgggagcag caatggtatg gcgtgggagt gacggattcc taccatggcc tggggagccc cgcagaggca gcgactatga agggtatcaa acccgtgtta ggaacaccaa cggaacggtc acgcgttgca aaatccagaa ctttcagtct atcagccctg ctgcttttga ggtaatacta gcatcggtgc cagggaccca ttaatctatt <210> 115 <211> 480 <212> PRT <213> Asperilius niger <400> 115 Met His Leu Pro Gin Arg Leu 1 5 Val Thr Ala 10 Ala Cys Leu Cys Ala Ser Ala Thr Ala Phe Ile Pro Tyr Thr Ile 25 Ile Ser Ala Arg Asp Ser Leu Ala Arg 40 Lys Leu Asp Thr Ser Asp Asp Val Pro Lys Arg Phe Leu Pro Pro Ser Asp Ala Leu Ala Asp Asp Ser Thr Ser Ser Ala Ser Asp Glu 151 /282 Ser Leu Ser Leu Asn Lys Arg Ile Pro Val Arg Arg Asp Asn Phe Lys Ile Val Val1Ala Glu Thr Pro Trp Ser Asn Leu Asp Gin Gly Ser Asp 115 Asp 100 Gly Ser Asp Ile Tyr Ile Ser Val Thr Ala Ala Val Asn Ile 110 Gly Gly Ser Giu Lys Ser Met Tyr 120 Met Leu Leu Asp Asp Thr 130 Trp Val Phe Gly Ser 135 Asn Cys Thr Ser Th r 140 Pro Cys Thr Met His 145 Asn Thr Phe Gly Ser 150 Asp Asp Ser Ser Th r 155 Leu Giu Met Thr Se r 160 Glu Glu Trp Ser Gly Tyr Giy Thr Ser Val Ser Giy Leu Leu 175 Gly Lys Asp Lys Leu Thr Ilie Ala 180 Vai Thr Val Arg Met Thr Phe 190 Pro Met Asp Gly Leu Ala 195 Ser Asn Ala Ser Asp 200 Asn Phe Giu Ser Tyr 205 Gly Ilie 210 Leu Gly Leu Gly Arg 215 Thr Asn Asp Ser Ser Tyr Asp Asn Pro 220 Phe Lys Ser Asn Ile Thr 225 Phe Met Asp Ala Ala Giu Ser Asn Val Gly Phe Ala Leu 245 Ser Arg Ser Pro Lys Asp Gly Thr Val Ser 255 Phe Gly Thr Asp Thr Val 275 Thr 260 Asp Lys Asp Lys T yr 265 Thr Gly Asp Ile Thr Tyr Thr 270 Asp Asp Val Gly Ser Asp Ser Tyr 280 Trp Arg Ile Pro Val1 285 Tyr Vai Gly Gly Thr Ser Cys Asp Phe Ser Asn Lys Ser Ala Ile Ile 152 /282 Asp 305 Thr Gly Thr Ser Ala Met Leu Pro Ser Ser Asp Ser Lys 315 Leu His Ser Leu Ile 325 Pro Gly Ala Lys Ser Gly Ser Tyr His Ile 335 Ile Pro Cys Asn Tyr Thr 355 Thr Thr Thr Lys Gin Val Ala Phe Ser Gly Val 350 Ser Gly Ser Ile Ser Pro Lys Asp 360 Tyr Val Gly Ala Thr 365 Gly Cys 370 Val Ser Asn Ilie Ser Tyr Asp Leu Gly Asp Asp Ilie Trp 385 Tyr Leu Leu Gly Asp Asp Giu Leu Arg 405 Phe Leo Lys Asn Tyr Ala Val Phe Val Gly Phe Ala Glu 410 Arg Ser Ser Asn Thr Thr 415 Ser Ala Ser Thr Thr Thr 435 Ser Thr Ser Ser Thr Ser Ser Thr Ser Gly Ser 430 Ser Ser Ser Gly Ser Ser Thr Thr Thr Ser Ser Al a 445 Ser Ser 450 Ser Asp Ala Giu Ser 455 Gly Ser Ser Met Ile Pro Ala Pro Gin 465 Tyr Phe Phe Ser Leu Ala Ile Ala Phe Met Leu Trp <210> 116 <211> 1099 <212> PRT <213> Aspergilius niger <400> 116 Met Leu Arg Gly Leu Arg Asp Val Val Leu 1 5 10 Leo Gin Phe Ala le Pro Leu Phe Leo Leu Leu His Phe Arg Leu 25 Ser Leu Arg Gly Val Ilie Thr 153 /282 Gly Phe Giy Ser Lys Ser His Phe 40 Gin Arg Pro Leu Ser Lys Met Ser Ser Thr Gin Lys Ser His Lys Leu Leu Gin Phe Lys Pro Giu 00 Ser Pro Ser Giu Phe Aia Gin Tyr Giu Ser Giu Arg Thr Giy Arg Vai Val Val Asp Gin Lys Gly Lys Vai Thr Giy Tyr Phe Val Leu Ala Thr 100 Giu Ile Leu Asp Asp Ser Gly Aia Pro 105 Arg Asn Tyr Arg Tyr 125 His Thr Leu 110 Lys Giy Phe Giu His Leu 115 Cys The Met Gly Ser 120 Leu Asp 130 Lys Leu Ala Thr Vai Tyr Ser Ser Thr Asn Aia Trp Thr 140 Ala Giy Trp Giu Giy Aila 145 Thr Asp His Thr Ala 150 Tyr Thr Leu Asp Phe Ala Gin Ile Leu 165 Pro Val Tyr Leu His Val Ile Ala Pro Thr 175 Leu Thr Asp Giy Asp Asp 195 Gly Cys Tyr Thr Val His His Ile Asp Gly Ala 190 Val Gin Asn Ala Giy Val Vai Tyr 200 Ser Giu Met Gin Gly 205 Asn Ser 210 Ala Giu Leu Ile Asp 215 Leu Thr Ala Arg Arg 220 Leu Thr Tyr Pro His 225 Gly Val Gly Phe Tyr Giu Thr Giy Met Met Giu Gin Leu 240 Arg Val Leu Thr Al a 245 Asp Arg Ile Arg Phe His Arg Giu Met Tyr 255 Gin Pro Lys Leu Cys Leu Ile Ile 265 Thr Gly Giu Vai Asp His Gin 270 154 /282 Asn Met Len 275 Gin Thr Len Asp Lys 280 Phe Giu Asp Thr Ile 285 Leu Asp Val Ilie Pro 290 Ser Pro Asp Ser Phe Lys Arg Pro Trp, 300 Val Asp Ser Lys Ala Pro Pro Len Gin 310 Lys Ser Ile Val Gin 315 Thr Val Gin Phe Gin Gin Asp Gin Asp Cys Thr Asp 340 Phe Gly Giu Ile Ile Arg Phe Leu Gly Pro 335 Tyr Len Ala 355 Pro Val Gin Thr Ser Ser Ala Ser 360 Gly Ala Vai Asn Val 345 Len Leu Asp Asn Ile 365 Ala Len Len 350 Len Val Gin Gly Lys Gin 370 Gin Leu Ala Ser Vai Tyr Tyr Ala Thr Glu Asp His 380 Gin Thr Gin Lys Pro Leu Ile Giu Ile Arg Ph e 390 Thr Len Thr Ser Val1 395 400 Met Gin 415 Ala Lys Val Gin Arg Phe Phe Gin Len Lys Asp Aia Lys Asp Len Arg Thr Trp 435 Asp 420 Met Arg Tyr Ile Lys 425 Gin Cys Ile Asp Arg Gin Arg 430 Phe Ala Gin Lys Phe Ser Thr Ser Ser Ala Ser Ser 445 Tyr Vai 450 Ile Ser Asp Phe Phe Giy Lys Arg Gly Ser Thr Met Len 465 Asp Vai Ala Thr Len 470 Gin Gin Tyr Asp Val1 475 Len Gin Lys Trp Gin Gin Gin Trp Ser Phe Ile Lys Trp Ile Ser Asp Ala Asn 495 His Val Thr Ile 500 Len Giy Val Pro Ser 505 Vai Lys Met Ser Asp Thr Len 510 155 /282 Lys Lys Giu 515 Glu Giu Ala Arg Val Ala Giu Gin Lys 520 Lys 525 Arg Leu Gly Asp Giu 530 Gly Leu Lys Lys Leu 535 Ala Asp Lys Leu Lys Ala Lys Ala Giu 545 Asn Asp Lys Giu Pro Lys Giu Met Giu Arg Phe Gin Pro Gly Ile Glu Ser 565 Ile His Phe Val Asp 570 Thr Thr Thr Ala Arg Ser 575 Gly Ala Ala Val Asp Ala 595 Leu 580 Asp Ala Gly Arg Ser His Lys Ala Gin Lys Leu 590 Asp Gly Ser Asp Leu Pro Leu Phe Ile His Phe Giu His Ilie Pro 610 Ser Ser Phe Val Gin 615 Leu Ser Leu Leu Ser Ala Gin Ala Val Pro Val Gin Leu 625 Phe Asn Leu Pro Val 645 Arg 630 Pro Leu Leu Ser Tyr Thr Glu Aia Ph e 640 Asn Arg Asn Gly Giu 650 Thr Ile Asn Phe Giu Gin 655 Vai Val Val Ala Arg Ser 675 Glu 660 Leu Glu Arg Asp Val Gly Tyr Ser Met Giu Gly 670 Phe Gin Val Leu Gly Asn Ser Met Leu Arg Ile Ser 685 Giu Leu 690 Giu Lys Tyr His Thr 695 Ala Ilie Ala Trp Ile Gin Giu Leu '700 Ala Ile Thr Ser Ser Trp 705 Asn Ser Ile Phe Asp 710 Val Giu Arg Leu Arg 720 Leu Leu Ser Asp Pro Asp Ser Lys Arg 730 Ser Giy Asp Asp Met Leu 735 Ala Ala Val His 740 Val Met Val His Ala Ala Glu Ser Ile Val Arg 750 156 /282 Ala Arg Ser 755 Thr Leu Val Lys Al a 760 Arg Tyr Leu Lys Ile Lys Lys Gin Leu 770 Ala Glu Glu Pro Ser Val Val Ala Met Glu Glu Ile Arg 785 Asp Ala Leu Phe Phe Glu Asn Met Val Leu Val Ile Al a 800 Asp Leu Glu Lys Le u 805 Gin Asn Pro Val Ser 810 Aia Trp Lys Pro Phe Ala 815 Giu Arg Leu Pro Leu Leu 835 Ala Giy Ala Pro Gin Pro Ile Thr Thr Arg Arg 830 Ser Tyr Val Ser Glu Ala Glv Gin 840 Lvs Leu Gly Gly Val Pro 850 Met Pro Thr Ile Ser Ser Phe Ala Tyr Ala Thr Ala Arg 860 Ala Leu Met Val Ala Gly 865 Leu Asp Ser Tyr Asp 870 Asp Pro Arg Leu Pro 875 Ile Ala Tyr Met Ala Val Glu Gly Leu Trp Val Ala Val Arg 895 Gly Lys Gly Gly Phe Val 915 Leu 900 Ala Tyr Gly Thr Phe Ala Tyr Asn Ile Asp Thr 910 His Lys Ala Asn Phe Asp Val T yr 920 Arg Ser Pro Asn Phe Asp 930 Ser Ser Lys Gln Val Glu Asp His Ser Gly Ala Met Pro 945 Phe Asp Pro Leu Met 950 Leu Glu Gly Ser Ile Ser Ser Ile Val 955 Ser Phe Ala Asn Gin Ser Thr Ile Ser Ala Ala Ser Gly Ser 975 Phe Ile Arg Gin 980 Val Ile Arg Arg Leu 985 Pro Ser Asp Tyr Lys Glu Arg 990 157/I282 Val Leu Lys Gin Val Arg Ala Thr Ser Val Asp Asp Val Lys Gly Ala 1000 1005 Leu Lys 1010 Ile Val 1025 Gly Leu 1040 Glu Phe 1055 Glu Glu 1070 Asp Glu 1085 Asp lie lie Leu Val Thr Cys Ala Pro 1015 Thr 1030 Leu Phe Asn Pro Val Leu Glu Glu Gin Ala Ser Gly Phe Thr Pro Ala Val Glu Asp Asp Tyr Ser Asp Asp Asp Asp Asp Ser Asp 1045 Gly 1060 Asp 1075 Glu 1090 Ser 1020 Thr 1035 Gin 1050 Asp 1065 Thr 1080 Asp 1095 Thr Ala Asn Ile Lys Glu Pro Leu Lys Asp Glu Asp Gly Ser Glu Glu Asp Asp Leu Lys Val Gly Asp Glu Tyr Glu Asp Met Glu Asp <210> 117 <211> 726 <212> PRT <213> Aspergillus niger <400> 117 Met Gly Ala Leu Gin Trp Leu Ser Ile Thr Ala Ala Ala Ala Ser Ala Val Ser Ala Thr Pro Glu Gin Ile Gly Ala Pro Arg Arg Thr Ser Thr Ser Glu Val Ile Pro Asn Pro Ser Gly Asp Thr Gly Leu Gin Trp Ser Phe Asp Thr Ser Glu Ser Thr Trp Trp Ser Leu Ile Leu Gin Ser Gly Lys Thr Thr Thr Leu Thr Asp Asp Ser Asp 158/282 Giu Glu Ile Ile Leu Gly Ser Asp Asn Ser Thr Leo Leu Tyr Ile Asn Ser Thr Asn 100 Ala Gin Vai Pro Gly 105 Gly Val Giu Leo Trp Ile Ala 110 Leo Ser Ala Asp Ser Ser 115 Asp Phe Ala Asn Tyr Lys Ala Ala Ser 125 Gly Phe 130 Leo Gly Ile Lys Thr Val Thr Asp Gly Asp Val His Ile Leo Arg Gly Lys 150 Ser Tyr Pro Asn Thr Ala Tyr Asn Gin Leo Ala Glu Tyr Pro Ser Thr Arg Ile Tyr Asp Ser Ile 175 Phe Val Arg Phe Ser Gly 195 Trp Asp Thr Tyr Thr Thr Ala Ser His Ala Val 190 Asn Val Gin Thr Leo Gin Ser Ser 200 Thr Ser Asp Asp Tyr Thr 210 Ser Ser Gly Gly Leo 215 Thr Asn Leo Val Pro Val Lys Gly Glu Ser Pro Phe Pro Phe Gly Gly As n 235 Asp Asp Tyr Asp Leo 240 Ser Pro Asp Gly Trp Val Thr Phe Lys 250 Ser Lys Ala Pro Glu Leo 255 Pro Leo Ala Gly Ser Ala 275 As n 260 Asn Thr Ala Ala Tyr 265 Val Tyr Leo Val Pro His Asp 270 Pro Ala Thr Thr Ala Phe Ala Asn Gly Pro Asp Pro Glu 290 Gly Val Glu Giy Ser Asn Asn Pro Val Phe Ser Pro Asp 300 Asn Thr Tyr Gbu Ser Ser 305 Asp Lys Ie Aia T yr 310 Phe Gin Met Aia 159 /282 Asp Arg Asn Val Leu 325 Tyr Val Tyr Ser Ala Asp Asp Thr Ile Thr 335 Pro Leu Ala Asp Trp Asp Arg Ser Pro Ser Ser Val 345 Thr Trp Val 350 Arg Thr Arg Asp Gly Asp 355 Asn Leu Vai Val Ser Gin Asp Leu Gly 365 Leu Phe 370 Ala Ile Pro Gly Asp 375 Ala Gly Asp Asp Lys Pro Thr Asn Ph e 385 Thr Asp Gly Gly Val Ser Ala Gin Val Leu Ser Asn Thr Leu Leu Val Thr 405 Ser Ser Ala Phe Thr Ser Trp Ser Val Tyr 415 Thr Ala Ser Giu Ile Asp 435 Asp Glu Gly Val Ile 425 Asn Thr Leu Ala Ser Ala Asn 430 Phe Giu Glu Pro Glu Leu Ser Leu Ser Ser Ser Phe Tyr 450 Phe Asp Gly Asn Trp 455 Thr Thr Leu Gin Gly Trp Ile Thr Tyr 460 Leu Ala Phe Leu Ile Pro 465 Gin Asp Phe Asp Ser Lys Lys Tyr His Gly Gly Pro Giu 485 Asp Ala Trp Ala Asp Glu Trp Asn Leu 490 Lys Trp 495 His Ser Lys Pro Thr Gly 515 Val1 500 Phe Ala Asp Gin Gly 505 Tyr Val Val Vai Gin Pro Asn 510 Ala Ile Gin Ser Thr Gly Phe Gin Gin Leu Thr Asp 525 Leu Asn 530 Trp Thr Gly Ala Tyr Asp Asp Leu Thr 540 Lys Ala Trp Gin Tyr 545 Val His Asp Thr T yr 550 Asp Phe Ile Asp Thr Asp Asn Gly Val 555 160/282 Ala Gly Pro Ser Gly Ala Phe Met Ile 570 Thr Trp Ile Gin Gly Asp 575 Asp Phe Gly Ilie Gly Asp 595 Arg 580 Lys Phe Lys Aia Leu 585 Vai Ser His Asp Gly Pro Phe 590 Val Glu His Ala Trp Val Glu Asp Giu Leu Trp Giu Phe 610 Asn Gly Thr Phe Gin Aia Arg Asp Aila 620 Phe His Asn Thr Asp 625 Pro Ser Gly Pro Se r 630 Arg Vai Leu Aia Ser Thr Pro Gin Val Ile His Ser Asp 645 Lys Asp Tyr Arg Pro Val Ala Asn Gly Ile 655 Gly Leu Phe Asn Phe Pro 675 Asn 66ro0 Thr Leu Gin Giu Ar g 665 Giy Val Pro Ser Arg Phe Leu 670 Asn Ser Leu Asp Giu Asp His Trp 680 Vai Thr Gly Gin Vai Trp 690 Tyr Gin Gin Vai Ser Asn Pro Asp 710 Gly Trp Ile Asn Arg Tyr Ser Gly Val 700 Asp Thr Vai Asn Pro Gly 705 Gly Ala Ile Ala Leu Giu 715 Val Val Asp Leu Asn Pro 725 <210> 118 <211> 564 <212> PRT <213> Aspergilius niger <400> 118 Met Thr Arg Gin Thr Ser Leu Val Pro Arg Leu Leu Thr Leu Ala Ser Leu Ala Ala Leu Ser Gin Ala Glu Leu 25 Gly Lys Ile Gin Trp Lys Gly 161 /282 00 Ser Cys Asn Leu Thr Thr Tyr Ala Leu Ilie Cys Gi y Thr Leu Asp Val Pro Tyr Asp Tyr Thr Glu Ser Asn Ser Ser Lys Thr Leu Thr Leu Asp Ilie Ala Lys Trp Pro 70 Ala Thr Lys Lys Pro Val Ser Glu Pro 00 Ile Phe Asn Phe Gly Gly Pro Gly Val Ser Phe Giu Gly Leu Gly Leu Tyr Gly Ile Ala Phe 115 Giu 100 Glu Phe Gin Ala Ilie 105 Leu Gly Gly His Asn Asp Leu 110 Phe Ser Cys Asn Asn Arg Gly Gly Asn Thr Ile Tyr Ser 130 Asp Asp Ala Thr Giu Leu Val Ala Gin Ala Pro Asn Asp 145 Ala Gly Arg Ala Ser Asn Ilie Ala Gin 165 Thr Ala Leu Gly Giu 155 Ile Trp Ala Gin Ala Cys Tyr Ala Thr 170 Asn Asn Gin Thr Gly Ser 175 Leu Ilie Gly Ala Leu Ser 195 Thr 180 Ser Phe Ala Ala Asp Ile Met Gin Val Ala Asp 190 Phe Ser Tyr Gly Lys Asp Ser Val Asn Tyr Trp Gly 205 Gly Thr 210 Thr Ile Gly Ala Leu Ala Ala Met Ph e 220 Pro Asp Arg Met Gly 225 Asn Val Ala Leu Asp 230 Gly Val Asp Asn Pro 235 Arg Giu Ala Leu Tyr 240 Gly Tyr Asn Ala Gin 245 Ala Val Val Asp Asp Lys Val Phe Giu Gly 255 Phe Cys Thr Cys Met Ala Ala Pro 265 Asp Leu Cys Pro Ile Ala Lys 270 162/282 Giu Tyr Thr 275 Ser Ala Ala Asn Leu 280 Giu Ala Ala Ile Leu Met Leu Glu Asn 290 Leu Lys Tyr Asn Ile Ala Ile Pro Thr Gly Gly Ile Val1 305 Thr Trp Ser Asp Val1 310 Lys Ser Thr Ile Glu Ala Met Tyr Leu 320 Pro Ser Ser Trp Leu Thr Ser Glu Leu Tyr Tyr Val Gin Thr 335 Arg Asn Thr Thr 340 Ile Leu Gly Asn Ser Glu Val Tyr Asp 345 Thr Ser Ala Ser Asp 365 Thr Ilie Lys 350 Giu Val Giy Ser Tyr Giy 355 Gin Ser Ala Ser Leu 360 Thr Ala 370 Ile Thr Cys Ser Lys His Arg Ser Thr Ile Lys Glu Leu Pro Tyr Val Lys 390 Ala Arg Gin Ala Thr Lys Ile Gly Asp Gly Ser Asp Asp Met Arg Cys Gin Trp Asn Pro Lys Met 415 Phe Ala Lys Pro Val Leu 435 Giu 420 Arg Tyr Ser Gly Asp 425 Phe Glu Val Lys Thr Ala Asn 430 Pro Leu Pro Ile Leu Ser Asn Tyr Asp Pro Ala Th r 445 Ala Ala 450 Lys Asn Leu Thr Thr Phe Glu Gly Val Leu Leu Giu Gin 465 Asn Gly Tyr Gly Thr Thr Leu Ser Pro Ser Leu Cys Ala Lys Ala Val Arg 485 Ala Tyr Phe Thr Asn 490 Giy Thr Leu Pro Ala Asp 495 Gly Thr Ile Gin Val Asp Val Leu Phe Thr Asn Leu Thr Tyr 510 163/282 Lys Asp Val 515 Asp Ala Thr 530 Trp Pro Lys Ser Gin Arg Ser Val Giu 525 Ser Arg Asp Ile Leu Lys Al a 535 Leu Met Ser Val Asp Lys Met Ser Arg Arg Arg Met Cys Ile 545 550 Tyr Leu Tyr Thr Ser Ala Ser Trp Pro Glu Leu Pro <210> 119 <211> 526 <212> PRT <213> Aspergilius niger <400> 119 Met 1 Tyr Tyr Ser Trp Val Ala Ala Leu 10 Val Ala Ala Leu Pro Val Ser Arg Ala Gly Tyr Leu Gin Phe Val Ala Pro Pro 25 Thr Asp LeuTile Pro Thr Lys Thr Gly Ile Asp Ile Pro Val Tyr Lys Gin Val Pro Cys Giu Thr Asp Pro Ser Val Lys Ser Phe Ser 55 Gly Tyr Val Asp Val Giu His Glu His Ile Phe Phe Trp Phe Glu Ala Arg Asn Asp Pro Thr Giu Pro Leu Thr Val Ile Asn Gly Gly Met Ser Asp Pro Gly Gly Pro Cys 115 Pro 100 Gly Ser Ser Ser Ile Gly Leu Phe Gin Giu His 110 Asn Pro Tyr Gly Ilie Asp Ala As n 120 Gly Ser Val Tyr Ser Trp 130 Asn Asn Ala Ser Met Leu Tyr Ile Gin Pro Val Gin Thr Gly Phe Ser Tyr Ser Ile Pro Val Pro Gly Tyr Val Asp Ser Ser 164/I282 145 Thr Asp Asn Gly Met Gly Ala Phe Gin Tyr Ser Arg Giu Thr 175 Phe His Phe Thr 180 Thr Glu Ser Tyr Gly 185 Gly His Tyr Gly Pro Val Phe 190 Gly Ala Lys Asn Giu Tyr 195 Ile Giu Giu Gin Ala His Leu Gin Pro 205 Lys Ile 210 Gin Leu Gly Ser Val1 215 Met Ile Gly Asn Gi y 220 Trp Tyr Asp Pro Ile 225 Ile Gin Tyr Gin Tyr Tyr Asn Phe Val Tyr Pro Gly Asn 240 Thr Tyr Asp Tyr Leu 245 Pro Phe Asn Lys Ile Ser Ser Leu Met Tyr 255 Asn Asn Leu Ala Ala Arg 275 Tyr 260 Gly Pro Gly Asn Leu Asp Gin Leu Tyr Asp Cys 270 Asp Phe Cys Gly Ile Asp Giu Cys Ser Thr Ala Asp 285 Ala Asn 290 Giu Val Giu Asn Val1 295 Tyr Asp Ile Tyr Gly Arg Asp Giu Tyr 305 Asp Phe Arg Giu Thr Pro Asp Pro Pro Tyr Giu Phe Val Asp Tyr Leu Asn 325 Lys Ala Ser Val Gin 330 Ala Ala Ile Gly Ala Tyr 335 Ile Asn Tyr Giu Ser Asn Asn Val Gly Leu Ala Phe Ser Ser 350 Val Gly Lys Thr Giy Asp Asp Gly Arg Leu Met 360 Asn Thr Ile Gin Asp 365 Leu Leu 370 Lys Gin Gly Val Th r 375 Val Vai Met Tyr Gly Asp Ala Asp Tyr Asn Cys Asn Trp Leu Gly Gly Giu Ala Val Ser Leu Gin Val Lys 165/I282 385 390 400 Ser Asp 415 Ala Ala Asn Phe Ser Ala Gly Tyr Thr 410 Asn Ile Val Thr Gly Val Thr Arg Val Tyr 435 His 420 Gly Gin Vai Arg Ala Gly Gin Phe Ala Phe Vai 430 Pro Leu Leu Giu Ser Gly His Val Pro Phe Tyr Aia Leu 450 Gly Lys 465 Giu Met Phe Giu Ilie Pro Ile Ser 470 Arg 455 Vai Ile Giy Giy Lys 460 Asp Val Ala Thr Ser Ser Leu Gin Vai Gly Thr Pro Ser Tyr Tyr Arg Giu 485 Gly Asn Ser Thr Ile 490 Gin Trp Giu Vai Leu Asp 495 Ser Leu Ala Thr 500 Tyr Asn Thr Thr Th r 505 Asn Ala Pro Asn Pro Vai Ser 510 Arg Arg Leu 515 Lys Arq Met Gly Ala Leu Arg Phe Gin Met 525 <210> 120 <211> 1156 (212> PRT <213> Aspergilius niger <400> 120 Met 1 Ser Cys Val Trp Leu His Ilie His 5 Arg Ser Leu Leu Ser Vai Ala Thr Asn As n Ser Val Ala Arg Ala Ala Ser Thr Ser Ala Ala Pro Pro Pro Pro Ser Ser Pro Pro Pro Gly Ser Asn Thr Tyr Ser Pro Leu Tyr Arg Pro Ilie Thr Asn 55 Pro Ilie Gly Phe Thr Leu Ser Pro Ala Ser Leu Val Ser Asn Pro Lys Phe Pro Ala Tyr Arg Arg 166 /282 Ser Arg His Phe Ser Leu Cys Pro Ala Al a 90 Ala Thr Pro Gly Val Thr Thr Ser Ile Pro Gly Gln Ala Val Arg Ser Leu Ser Ser Leu 110 Thr Asp Gin Ilie Ile His 115 Ser Thr Arg Pro Ala Ilie Arg Ile Met Asp 130 Leu Asn Gly Asp Al a 135 Gly Ala Lys Arg Lys 140 Arg Ser Ser Ile Thr 145 Thr Pro Ala Glu Arg 150 Asp Pro Val Lys His Ser Thr Pro Ala 170 Arg Pro Giu Ser Ala Leu Thr Pro Asn Gly Thr Val Tyr Asp 175 Val C-lu Asp Gin Ala Asp 195 Asp 180 Glu Asp Ala Ser Ar g 185 Leu Leu Pro Val Gly Pro Ala 190 Val Val Lys Ser Pro Glu Trp Ala Thr Ile Glu Ser Val 210 Val Ser Ile His Cys Gin Thr Cys Phe Asp Thr Giu Ser Met Ser Ser Gin 230 Ala Thr Gly Phe Val1 235 Val Asp Ala Glu Giy Tyr Ile Leu Asn Arg His Vai Val1 250 Cys Pro Gly Pro Phe Trp 255 Gly Tyr Cys Ile 260 Phe Asp Asn His Glu Cys Asp Val Arg Pro Val 270 Tyr Arg Asp 275 Pro Val His Asp Gly Ile Leu Lys Phe Asp Pro Lys 285 Ala Ile 290 Arg Tyr Met Lys Le u 295 Arg Glu Leu Lys Gin Pro Asp Ala Ala 305 Lys Val Giy Ser Ile Arg Val Val Asn Asp Ala Gly Giu 320 167/I282 Lys Leu Ser Ile Leu Ser Gly Val Ile 325 Ser Arg 330 Leu Asp Arg Asn Ala 335 Pro Giu Tyr Gly 340 Asp Gly Tyr Ser Asp 345 Phe Asn Thr Asn Tyr Ile Gin 350 Val Val Asn 00 Ala Ala Ala 355 Ala Ala Ser Gly Ci y 360 Ser Ser Gly Ser Ilie Asp 370 Gly His Ala Ilie Leu Gin Ala Gly Arg Ala Asp Gly Ala Thr Asp Tyr Leu Pro Leu Asp Arg 395 Pro Leu Arg Ala Giu Cys Ile Arg Arg 405 Gly Giu Pro Val Thr 410 Arg Giy Thr Ile Gin Thr 415 Gin Trp lie Pro Glu Trp 435 Lys Pro Phe Asp Cys Arg Arg Leu Gly Leu Thr 430 Giu Thr Ser Giu Ala Thr Val Lys Ala Ala Pro Thr 445 Met Leu 450 Val Ala Giu Ile Leu Pro Giu Gly Ala Asp Gly Lys Leu 465 Giu Giu Giy Asp Val1 470 Leu Leu Gin Val Gly Vai Leu Leu Gin Phe Ile Arg Leu 485 Asp Asp Ile Leu Ser Ser Val Gly Gin Thr 495 Val Arg Leu Gin Val Gly 515 Val Gin Arg Gly Gin Asn Val Glii Ile Giu Cys 510 Val Thr Val Asp Leu His Ala Ile 520 Thr Pro Asp Arg Ala Gly 530 Gly Thr Phe His As n 535 Leu Ser Tyr Gin Ser Arg Leu Tyr Al a 545 Ile Ala Thr Arg Gly 550 Val Tyr Val Cys Giu Ala Ala Gly Ser 555 168 /282 Lys Leu Glu Asn Leu Ser Gly Trp Ile 570 Ile Asp Ser Val Asp Lys 575 Arg Pro Thr Pro Asp Arg 595 Arg 580 Asn Leu Asp Glu Val Glu Val Met Arg Thr Ile 590 Arg Asp Leu Ser Arg Val Val Ile 600 Ser Tyr Arg His His Thr 610 Arg Gly Thr Ser Val Tyr Ile Asp His Trp His Pro Met Arg Leu Ala Val Arg Asn Asp Asp 630 Pro Ile Pro Ala Leu 650 Thr 635 Gly Leu Trp Asp Ser Asp Leu Ala Asp 645 Pro Pro Val Pro Arg Lys 655 Ala Asp Phe Ile Val Arg 675 Gin Leu Asp Gly Ser Gin Pro Ala Ala Ala Asp 670 Leu Lys Leu Ser Phe Val Arg Val 680 Ser Cys Thr Met Asp Gly 690 Tyr Pro Gin Ala Lys Thr Gly Phe Gly 700 Leu Val Val Asp Ala Glu Lys Gly Leu 705 Leu Cys Asp Ile Asn 725 Val 710 Val Val Ser Arg Ile Val Pro Tyr Val Thr Val Ala Ser Ile Ile Val Asn Ala 735 Lys Val Val Asp Pro Ser 755 Phe 740 Leu His Pro Leu Asn Tyr Ser Ile Ile Gin Tyr 750 Leu Ala Thr Leu Val Gin Ala Pro 760 Val Gin Ser Ala Asp Tyr 770 Ile Lys Gin Gly Asp Thr Ile Phe Val 780 Gly Phe Asn Gin Asn 785 Phe Arg Ile Val Val 790 Ala Lys Thr Ala Thr Asp Ile Thr 169/282 Val Ser Ile Pro Al a 805 Asn Ala Ser Ala Pro 810 Arg Tyr Arg Ala Ile Asn 815 Leu Asp Ala Ile 820 Thr Val Asp Thr Leu Ser Gly Gin Cys Ser Asn 830 Trp Leu Asn Gly Val Leu 835 Ile Gly Giu Asp Gly 840 Val Val Gin Ala Tyr Leu 850 Leu Gly 865 Gly Giu Arg Thr Phe Ala Thr Pro 870 Asn Ser His Lys Val Giu Tyr His Ser Leu Leu Pro Val1 875 Leu Ser Lys Val Gin 880 Gin Gly Giu Met Pro 885 Glu Leu Ara Ile Leu 890 Asn Met Giu Ser Tyr Val 895 Val Gin Met Giu Lys Val 915 Gin Ala Arg Ile Gly Val Ser Glu Giu Trp Ile 910 Phe Met Val Thr Gin Ala Asn Ser Arg His Gin Arg Lys 930 Val Asp Cys Pro Pro 935 Pro Gly Phe Asn Ala Ala Asp Thr Phe 945 Giu Glu Gly Asp Ile Leu Thr Leu Gly Gin Leu Ile Arg Val Ser Glu Asp Ile Met Tyr Lys Asp Thr Leu Giu Ala 975 Leu Ile Val Arg 980 Asn Gly Gin Giu Met 985 Arg Ile Gin Val Pro Thr Val 990 Pro Thr Glu 995 Asp Leu Giu Thr Asp Arg Ala Val Val Phe Cys Gly Ala 1000 1005 Val Leu Gin Lys Pro His His Ala Val Arg Gin Gin Ilie Ser Lys 1010 1015 1020 Leu His Ser Giu Val Tyr Val Ser Ala Arg Ser Arg Gly Ser Pro 1025 1030 1035 170 /282 Ser Tyr 1040 Asn Gly 1055 Ser Lys 1070 Phe Asp 1085 Tyr Phe 1100 Gly Trp 1115 Ile Ala 1130 Gly Phe 1145 Gin Tyr Gly Leu Val Pro Thr Pro Ile Pro Asp Asn Asn Val Pro Trp Pro Met Ser Glu Arg Thr Val Ser Pro Asp Ala Ala Asp Gly Val Ser Ala 1045 Asn 1060 Thr 1075 Val 1090 Tyr 1105 His 1120 Asn 1135 Asp 1150 Pro Thr Asn Phe Leu Asp Arg Phe Tyr Phe Arg Leu Val Thr Val Lys Ile Lys Asp Gin Asp Lys Asp Lys Leu Asn Pro Asp Ile Glu Pro Asp Ile 1050 Ser 1065 Arg 1080 Lys 1095 Ser 1110 Tyr 1125 Ala 1140 Thr Ala Val Glu Glu Val Ala Val Thr Asn Asp His Gin Pro Ser Lys Asp Gly Met Asp Glu Leu Glu 1155 <210> 121 <211> 536 <212> PRT <213> Aspergillus niger <400> 121 Arg Val Leu Pro Ala Ala Met Leu Gly Ala Ala Thr Ala Ala Val Pro Pro Ala Asp His Gin Gin Val Leu Gly Asn Gly Ala Lys His Gly Asp Gly Phe Ala Ala Glu Val Pro Ala Asp His Ser Ser Lys Pro Leu His Ala Gln Glu Glu Leu Lys Ser Leu Ser Asp Ala Arg Lys Leu Trp Asp Glu Val Ala Phe Phe Pro Glu Ser 171/282 Met Asp Gin Asn Leu Phe Ser Leu Lys Lys His Asn Arg Arg Pro Asp Ser His 100 Trp Asp His Ile Val1 105 Asp Gly Lys Leu Glu Ala Tyr 110 Ile Asp Pro Asp Leu Arg 115 Val Lys Lys Thr Pro Gly Ser Leu Gly Val 130 His Leu 145 Lys Gin Tyr Thr Phe Tyr Trp The 150 Tyr Leu Asp Asp Asn 140 Glu Asn Asp Lys Phe Glu Ser Arg Asp Pro Glu Asn Pro Val Val Leu Leu Asn Gly Giy Gly Cys Ser Ser Leu Thr 175 Gly Leu Phe Pro Val Tyr 195 Met 180 Giu Leu Gly Pro Ser 185 Ser Ile Asn Lys Lys Ilie Gin 190 Val Ile Phe Asn Asp Tyr Ala Asn Ser Asn Ala Leu Asp 210 Gin Pro Val Asn Gly Tyr Ser Tyr Ser 220 Asn Ser Ala Val Ser 225 Asp Thr Vai Ala Al a 230 Gly Lys Asp Val Ala Leu Leu Thr Phe Phe Lys Gin Pro Glu Tyr Ala Gin Asp Phe His Ile Ala 255 Gly Giu Ser Leu Ser His 275 Tyr 260 Ala Gly His Tyr Ilie 265 Pro Val Phe Ala Ser Glu Ile 270 Leu Ile Gly Lys Lys Arg Asn Asn Leu Gin Ser Asn Gly 290 Leu Thr Asp Gly Thr Gin Tyr Giu Tyr 300 Tyr Arg Pro Met Al a 305 Cys Gly Asp Gly Gly 310 Tyr Pro Ala Val Asp Glu Ser Ser 172/282 Gin Ser Met Asp Asn 325 Ala Leu Pro Arg Gin Ser Met Ile Glu Ser 335 Cys Tyr Ser Ser 340 Glu Ser Ala Trp Val1 345 Cys Val Pro Ala Ser Ile Tyr 350 Gin Asn Val Cys Asn Asn 355 Ala Leo Leo Ala Pro 360 Tyr Gin Arg Thr Tyr Asp 370 Val Arg Gly Lys Glu Asp Ser Ser Leu Cys Tyr Ser Met Gly Tyr Val Asp Tyr Leo Asn Lys 395 Pro Giu Val Ilie Glu 400 Ala Val Gly Ala Glu 405 Val Asn Gly Tyr Asp 410 Ser Cys Asn Phe Asp Ile 415 Asn Arg Asn Leu Val Pro 435 Leu Phe His Gly Trp Met Lys Pro Tyr His Arq 430 Tyr Ala Gly Gly Leo Leo Giu ile Pro Val Leu Ile 445 Asp Ala 450 Asp Phe Ile Cys As n 455 Trp Leo Gly Asn Lys Ala Trp Thr 460 Ser Ala Glu Leu Glu Al a 465 Leo Gbu Trp Pro Gly 470 Gin Ala Gbu Tyr Glu 480 Gly Gin 495 Asp Leo Val Ile Asp Asn Gbu His Gly Lys Lys Ile Val Lys Ser His Met Val 515 His 500 Gly Asn Phe Thr Phe 505 Met Arg Leo Tyr Gly Gly Gly 510 Phe Phe Asn Pro Met Asp Gin Pro 520 Glu Ser Ser Leo Arg Trp Leo Gly Gly Glu 530 <210> 122 <211> 279 <212> PRT Trp Phe 535 173 /282 <213> Aspergillus niger <400> 122 Met 1 Lys Phe Thr Asn Tyr Leu Leu Thr Thr 10 Ala Thr Leu Ala Ser Ser Val Leu Ala Ala Pro Ala Pro Arg Thr Gly Leu Giu Asp Arg Leu Arg ile Pro Leu Ala Arg Ser Leu Gin Arg Gin Ser His Pro Leu Ala Asp Thr Ser Thr Lys Giu Ser Arg Leu Leu Giu Ala Asp Giu Asn Thr Thr His Val Thr Ser Ser Asn Trp Gly Ala Val Arg Gi u s0 Gin Pro Pro Pro Gin Gly Thr Tyr Ser Ala 90 Val Ser Ala Thr Phe Arg Val Pro Giu Ala Trp Vai 115 Thr Ala Gin Gly Gly 105 Ser Gly Thr Gin Ala Gly Ser 110 Ile Leu Gin Giy Ile Asp Gly Thr Tyr Ser Asn Al a 125 Thr Gly 130 Val Asp The Tyr Val 135 Giu Asn Gly Gin Tyr Asn Asp Ala Trp 145 Tyr Giu Trp Tyr Asp Tyr Ala Tyr Phe Asp Leu Asp Ser Thr Gly Asp Thr Ile Val Ala Lys 165 Giu Ala Ilie Ser Pro Ser 175 Gin Gly Val Gin Thr Ile 195 Thr Ile Giu Asn Ilie 185 Ser Thr Gly Lys Lys Ala Thr 190 Giy Gin Asn Arg Ala Pro Ala Ala 200 Thr Ala Thr Leu Ala Asp 210 Trp Ile Val Gin Asp 215 Phe Gin Ser Gly Ser Met Val Asp 174 /282 Leu Ala Gly 225 Phe Gly Giu 230 Ile Ser Phe Trp Va Gi Al Gn Val Gln Ala Gln Gly Gly Ser Thr Trp 245 Gly Vai Asp Asp Ala 250 Thr Ile Val Glu Leu Lys 255 00 Gin Gly Asn Phe Thr Val 275 Giu 260 Val Leu Thr Asp Vai 265 Giu Val Gin Ser Asp Ser Ala 270 Lys Tyr Thr Ser <210> 123 <211> 573 <212> PRT <213>' Aspergilius niger <400> 123 Met I Ile Tyr Val Asn Tyr Ile Leu Gly 5 Leu Leu Ser Leu Leu Ala Val Ala Ile Pro Asp Thr Ala Pro Asp Tyr Val Val Asp Gin Leu Asn Ser Phe Thr Pro Gly Trp Thr Lys Ala Ala Pro Pro Pro Met Lys Phe Trp Leu Ser His His Glu Tyr Lys Ala Asp Phe Giu Lys Val Ile Asp Ilie Ser Thr Pro Gly Arg Asp Tyr Gly Arg His Met Lys Arg Asn Asp Val Met Aia Phe 90 Met Arg Pro Ser Asp Gin Val Ser Lys Asn Ala Ilie 115 Ilie 100 Ile Phe Ser Trp Giu Ser Glu His Val Pro Pro 110 Val Pro Leu Giu Asp Arg Gly Trp Val Ala Phe Thr 125 Ala Gin 130 Ala Gin Ser Met Met 135 Lys Thr Asp Phe Asn Phe His His Leu Giu Thr Asn Thr Thr Gin Ile Arg Thr Leu Lys Tyr Ser Val Pro 175/282 145 Glu Gin Val Asp His Leu Gin Met lle 170 Gin Pro Thr Thr Arg Phe 175 (N) 0 (N 00 0q 0D Gly Arg Pro Val Asn Ile 195 Lys 180 Thr Gin Thr Ser Leu 185 Pro Ser Leu Met Pro Val Ser 190 Val Thr Pro Asp Glu Ile Ser Asp Cys Leu Thr Ile Cys 210 Leu Arg Gin Leu Gly Leu Pro Ser Lys Ala Ser Pro Asp 225 Ser Arg Asn Val Leu 230 Gly Ile Ser Gly Tyr 235 Leu Asp Gin Tyr Ala 240 Arg Tyr Ser Asp Asp Glu Phe Leu Val Tyr Ser Pro Asn Ser 255 Val Asp Ala Gin Asn Ser 275 Asp 260 Phe Ser Val Val Ile Asn Gly Gly Gin Asn Pro 270 Ile Gin Tyr Gin Glu Gly Ser Thr 280 Glu Ala Ser Leu Asp 285 Ala Leu 290 Ser Met Ala Phe Ala Asn Ala Thr Tyr Thr Thr Ala Arg Ala Pro Ser Pro 310 Tyr Leu Glu Gin Gin Tyr Leu Val Gly 320 Leu Pro Asp Glu Asp 325 Leu Pro Ala Val Leu 330 Ser Thr Ser Tyr Gly Glu 335 Asp Glu Gin Phe Ala Gin 355 Leu Pro Glu Glu Thr Glu Ala Thr Cys Asn Leu 350 Ser Ser Gly Leu Gly Ala Arg Gly 360 Val Ser Val Ile Phe 365 Asp Ser 370 Gly Val Gly Gly Ser 375 Cys Val Ser Asn Asp 380 Gly Ser Gin Arg Thr Arg Phe Gin Pro Ile Phe Pro Ala Ser Cys Pro Phe Val Thr Ser 176/282 385 Val Gly Gly Thr Gi u 405 Gly Val Gly Pro Giu 410 Lys Ala Val Asp Phe Ser 415 Ser Gly Gly Phe Ser Glu Arg Phe 420 Ala Tyr Leu Ala Arg Arg Pro Ser Tyr Gin Asn Ala 430 Asp Gly Leu Ser Val Glu 435 Leu Gly Asp Lys Tyr Asn 450 Pro Asp Gly Arg Gi y 455 Ile Pro Asp Val Se r 460 Ala Gin Ala Ser Tyr Val Ile Arg His Gly Gin Trp Gin Thr Ala Giy Ser Ala Ala Ala Pro 485 Val Phe Ala Ala Val1 490 Ile Ser Arg Leu Asn Ala 495 Ala Arg Leu Leu Tyr Ser 515 Giu 500 Gin Gly Lys Pro Leu Gly Phe Leu Asn Pro Trp 510 Asp Gly Gly Leu Asp Gin Gin Phe Thr Asp Ile Ser Val 530 Gly Cys Asp Gly Asn Gly Gly Ala Le u 540 Val Pro Tyr Ala Ser 545 Trp Asn Ala Thr Lys 550 Gly Trp Asp Pro Thr Giy Leu Gly Pro Leu Tyr Gin Th r 565 Leu Glu Gin Leu Gin Ser Ala <210> 124 <211> 585 <212> PRT <213> Aspergillus niger <400> 124 Met Arg Ser Ser Gly Leu Tyr Thr Ala Leu Cys Ser Leu Ala Ala Ser Thr Asn Ala Ile Val His Giu L~s Leu Ala Ala Val Pro Ser Gly 177 /282 Trp His His Val Giu Asp Ala Giy Ser Asp His Gin Ile Ser Leu Ser 40 Leu Asp Gin Leu Giu Ser Lys Leu Lys Ile Ala Leu Ala Arg Lys Asn 55 Leu Ser Thr Pro Giu Ser Gin Tyr Gly Gin Trp Leu Asp Giu Asp Vai Asp Thr Leu Phe Pro Val Ser Asp Lys Ala Vai Ile Asn Trp Leu Leu Val Asn 115 Arg 100 Ser Ala Asn Ilie Thr 105 His Ile Ser Arg Gin Giy Ser 110 Leu Leu Asn Phe Ala Thr Thr Asp Lys Val Asn Ala Thr 130 Phe Ala Tyr Tyr Gin 135 Ser Gly Ser Ser Gin 140 Arg Leu Arg Thr Giu Tyr Ser Ile Asp Asp Leu Val Asp 155 Ser Ile Asp Leu Ser Pro Thr Thr Phe 165 Phe Gly Lys Giu Thr Thr Ala Gly Leu Asn 175 Gin Arg Ala Ser Ser Cys 195 Gin 180 Lys Ile Asp Thr His 185 Val Ala Lys Arg Ser Asn Ser 190 Giu Met Tyr Ala Asp Val Ile Leu Ser Cys Leu Asn Phe 210 Gly Asn Tyr Thr Pro 215 Ser Ala Ser Ser Gly 220 Ser Lys Leu Gly Phe 225 Gly Ser Phe Leu Giu Ser Ala Ser Ser Asp Leu Ala Phe Giu Lys Leu Phe 245 Asn Leu Pro Ser Ser Phe Ser Val Giu Leu 255 Val Asn Gly Val Asn Asp Gin Asn 265 Gin Ser Thr Ala Ser Leu Thr 270 178/282 Glu Ala Asp 275 Leu Asp Val Giu Le u 280 Leu Val Gly Val Hi Pr Le His Pro Leu Pro Val 290 Thr Giu Phe Ilie Ser Gly Glu Pro Ala Asp Asn Glu Asn 305 Glu Pro Tyr Leu Gin 310 Tyr Tyr Giu Tyr Leu 315 Leu Ser Lys Pro Ser Ala Leu Pro Val Ilie Ser Asn Tyr Gly Asp Asp Glu Gin 335 Thr Val Pro Vai Gly Leu 355 Giu 340 Tyr Tyr Ala Lys Val Cys Asn Leu Ile Gly Leu 350 Asp Glu Gly Arg Gly Ile Ser Val 360 Leu Giu Ser Ser Gly 365 Ilie Gly 370 Ser Gly Cys Arg Thr 375 Thr Asp Gly Thr Asn Arg Thr Gin 380 Thr Ala Val Gly Ph e Gi y Asn 385 Pro Ile Phe Pro Thr Cys Pro Tyr 400 Gly Gly 415 Thr Met Ser Tyr Al a 405 Pro Gli Ile Ala Trp 410 Glu Ala Ser Ser Phe Ser Asn Asn Tyr Leu 435 Phe Glu Arg Ala Trp 425 Phe Gin Lys Glu Ala Val Gin 430 Tyr Tyr Ser Ala His His Ile Asn Giu Thr Lys Gin 445 Gin Phe 450 Ala Asn Phe Ser Arg Gly Phe Pro Asp 460 Val Ala Ala His Ser 465 Phe Giv Pro Ser Tyr 470 Giu Val Ilie Phe Giy Ala Arg Tyr Gly 480 Ser Gly Gly Thr Ala Ala Cys Pro Phe Ser Ala Leu Val Gly 495 Met Leu Asn Asp 500 Ala Arg Leu Arg Ala 505 Gly Lys Ser Thr Leu Gly Phe 510 179 /282 Leu Asn Pro 515 Leu Leu Tyr Ser Lys 520 Gly Tyr Arq Ala Leu 525 Thr Asp Val Thr Gly 530 Gly Gin Ser Ile Gi y 535 Cys Asn Gly Ile Pro Gin Asn Asp 00 Giu 545 Thr Val Ala Gly Gly Ile Ile Pro Ala His Trp Asn Ala 560 Thr Val Gly Trp Asp 565 Pro Vai Thr Gly Leu 570 Gly Leu Pro Asp Phe Giu 575 Lys Leu Arg Leu Val Leu Ser <210> 125 <211> 265 <212> PRT <213> Aspergillus niger <400> 125 Met 1 Lys Thr Thr Ala Leu Leu Thr Ala 5 Gly 10 Leu Leu Ala Thr Thr Ala Met Ala Ala Ser Thr Asn Pro Leu Thr Ala Lys Arg 25 Gin Ala Ala Arg Ala Lys Arg Thr Asn Glu Arg Gin Ser Asn Pro Phe Lys Pro Val Leu Ala Leu Asn Gly Lys Asn Val Glu Tyr Ser Ser Asn Trp Ala Val Thr Ala Glu Gly Ala Val Leu Ile Gly Thr Gly Tyr Phe Val Val Pro Thr Pro Ser Val Pro Gly Gly Ser Ser Arg Giu Giu Tyr Cys Thr Ala Ile 115 Al a 100 Ser Ala Trp Val Ile Asp Gly Asp Thr Cys Asp 110 Gly Ser Glu Leu Gin Thr Gly Asp Phe Cys Val 180/282 00 00 Val Ser 130 Phe Asp Ala Trp Tyr 135 Glu Trp Tyr Pro Asp 140 Tyr Ala Tyr Asp Phe 145 Ser Gly Ile Ser Ser Ala Gly Asp Ile Lys Val Thr Asp Ala Ser Ser Asp 165 Thr Thr Gly Thr Al a 170 Thr Ile Glu Asn Val Ser 175 Thr Gly Thr Leu Cys Giu 195 Val Thr His Ser Thr Gly Gly Val Asp Gly Asp 190 Giu Glu Asp Tyr Asn Ala Glu Ile Val Glu Asp Asp Ser 210 Leu Val Pro Phe Asp Phe Gly Thr Val Thr Phe Thr 220 Pro Glu Asp Ala Ser Cys 225 Ser Ala Thr Lys Gly Ser Ser Val Gly 235 Th r 240 Ile Ile Asp Ile Giu 245 Gin Asn Glu Val Thr Ser Val Ser Val Ser 255 Ser Ser Giu Vai Val Lys Tyr <210> 126 <211> 580 <212> PRT <213> Aspergilius niger <400> 126 Met 1 Val Ala Phe Arg Ile Ser Ala Phe Ala Leu Ala Ala Pro Ala Leu Ala Trp, Lys Leu Val Val Leu Glu Val Lys Ser Val Pro Ser Asp Ser Leu Ser Val Giu Ala Ala Asp Thr Ser Ser Thr Val Ala Leu Ala Arg Gin Asn Leu Asp Gin Leu 55 Gi u Glu Lys Leu Leu 181 /282 Ala Val Ser Thr Pro Gly 70 Lys Asp Thr Tyr Gly Gin Phe Leu Asp Asp Ala Ala Asp Asp Asp Ile Asn Gin Phe Pro Leu Val Val Ala Trp Leu Leu Leu Asn 115 Lys Ala Gly Val Gin Ilie His Lys Glu Gly Gly 110 Leu Leu Asn Phe Ala Thr Thr Val 120 Gly Thr Ala Asn Thr Thr 130 Phe Ser Vai Tyr Ser Gly Ser Thr Lys Leu Arg Thr Thr 145 Gin Tyr Ser Vai Pro 150 Asp Giu Leu Thr Giy 155 Ser Ile Asp Leu Ile 160 Ser Pro Thr Val Phe Gly Lys Ser Ala Ala Arg Ser Ala Ala 175 Vai Arg Ala Asn Val Cys 195 Gin Thr Thr Lys Thr Ser Arg Lys Lys Ser Ser 190 Gin Tyr Ser Giu Tyr Ile Thr Asp Cys Leu Lys Ilie Asp 210 Tyr Thr Pro Giu Ser Ser Gly Ser Val Gly Phe Gly Ser 225 Phe Leu Asn Giu Ala Leu Tyr Ser Leu Asp Leu Phe Th r 240 Gin Tyr Phe Asp Ile 245 Pro Gin Gin Ser Ph e 250 Thr Val Giu Thr Ile Asn 255 Gly Gly Ile Asp Val Gin 275 Asn 260 Asn Gin Giu Asn Asp 265 Pro Asp Gly Giu Ala Asp Leu 270 Val Thr Glu Asn Ile Val Gly Ser His Pro Leu Pro 285 Tyr Ilie 290 Thr Gly Gly Ser Pro Phe Ile Pro Val Giu Thr Thr 182/I282 Th r 305 Asp Glu Asn Glu Tyr Leu Gin Tyr Tyr Glu Tyr Leu 315 Ser Asn Ser Tyr Leu Lys Thr Asn Asp Glu 325 Leu Pro Leu Val Gly Asp 335 Asp Giu Asp Ile Gly Leu 355 Val Pro Ile Ala T yr 345 Ala Thr Arg Val Cys Asn Leu 350 Ser Ser Gly Met Giy Thr Arg Ile Ser Ile Leu Asp Ser 370 Gly Val Gly Gly Al a 375 Cys Met Ser Asn Asp 380 Gly Thr Asp Lys Th r 385 Glu Phe Thr Pro Phe Pro Gly Thr Pro Tyr Ile Thr Val Gly Gly Thr Gin 405 Asp Val Pro Giu Val 410 Ala Trp Val Asp Ser Ser 415 Gly Giy Phe Val Glu Thr 435 Asn Tyr Phe Ser Pro Ser Tyr Gin Ser Asp Gin 430 Lys Lys Tyr Tyr Leu Asp Lys Ile Ser Ala Ser Thr 445 Tyr Glu 450 Gin Tyr Thr Asn Phe 455 Ser Gly Arg Ala Pro Asp Val Ser Al a 465 The Ala Gly Ser Tyr Tyr Glu Thr Ile Asp Gly Gin Gly Leu Val Ala Gi y 485 Thr Ser Gly Ala Ser 490 Pro Val Phe Ala Gly Ile 495 Val Ala Leu Gly The Leu 515 Asn Asp Ala Arg Arg Ala Asn Lys Thr Ser Leu 510 Ser Leu Asn Asn Pro Trp Leu Ser Ser Gly Tyr Lys 525 Asp Ile 530 Thr Ser Gly Giu Al a 535 Val Gly Cys Gin Asp Val Glu Gly 183 /282 Ala Gly Val Ile Pro Trp Ala 545 550 Ser Trp Asn Al a 555 Thr Thr Gly Trp Asp 560 Pro Ala Thr Gly Leu Gly Thr Pro Asn Phe 565 570 Ala Lys Leu Lys Glu Ala 575 Val Leu Ala Leu 580 <210> 127 <211> 631 <212> PRT <213> Aspergillus niger <400> 127 Met 1 His Gly Leu Arg 5 Leu Val Cys Ser Gly Thr Leu Pro Leu Val Ile Leu Ala Asp Leu Asp Tyr Pro Ala Ala Ser His Thr Thr Ser Ala Ala Val Val Asn Ser Ser Leu Arg Leu Thr 40 Ser Asn Ser Glu T yr Val His Val Asp Thr Asn Arg Ser Val Ala Val Ala Glu Glu His Tyr Thr Asp Thr Ala Arg Leu Val Gin Asn Ile Val Pro Gly Ser Phe Arg Leu Ile Asp Asp His Phe Gly Asp Asn Gly Val Ala His Val Tyr Phe 100 Arg Gin Thr Leu Gly Ile Asp Ile Asp Asn Ala 110 Asp Phe Asn 115 Val Asn Ile Gly Asp Gly Leu Val Ser Phe Gly His Ser 130 Phe Phe Thr Gly Al a 135 Leu Pro Ser Ser His Leu Asp Asn Thr 140 Ala Arq Asp Ala Ile Asn 145 Val Leu Ser Pro Ala Ala Leu Arg Gly 155 Gin Leu Pro Leu Thr Ile Asp Asn Val Ser Thr Giu Ala Ala Giu Gly 184 /282 Arg Asn Glu Lys Ala Lys 195 Tyr 180 Ile Phe Arg Giu Al a 185 Val Gly Ala Val Ser Asp Pro 190 Leu Ala Leu Leu Val Tyr Leu Lys Pro Glu Gly Thr 205 Thr Trp 210 Ile Asp 225 Arg Ile Giu Thr Ala Giu Thr Thr 230 Met Tyr Glu His Leu Leu Thr Tyr Thr Val His Gly Val1 235 Val Asp Tyr Val Al a 240 Asp Ala Thr Tyr Val Tyr Pro Trp Thr Asn Asp Pro Ala Glu 255 Gly His Arg Tyr Thr Trp 275 Thr 260 Ile Val Thr Asp Trp Asp Leu Ser Ala Ser Ala 270 Thr Arg Gly Ile Ser Asp Gly Arg 280 Asp Asn Tyr Thr Thr 285 Asn Asn 290 Ala Ile Ala His Trp 295 Asn Pro Thr Gly Gly Ser Tyr Leu Asn Leu Arg Pro Asp Pro Asn Leu Asn 315 Phe Gin Trp Pro Ser Pro Asn Met Ser 325 Pro Pro Arg Ser Ile Asn Ala Ser Ile Val 335 Gin Leu Phe Gly Phe Thr 355 Tyr 340 Thr Ala Asn Ala His Asp Leu Leu Tyr Thr Leu 350 Ser Ala His Glu Ser Ala Gly Phe Gin Trp Asn Asn 365 Gly Gly 370 Arg Asp Lys Asp Val Ile Leu Asn Ala Gin Asp Gly 380 Asp Gly Ile Pro Se r Gi y 400 Phe Ser Asn Ala Asn 390 Phe Ala Thr Pro Pro 395 Arg Met Arg Met Tyr Ile Trp Ile Glu Ser Thr Pro Ser Arq Asp Gly 185/I282 405 Ser Phe Asp Al a 420 Gly Ile Val Ilie His Glu Tyr Thr His 425 Asn Ala Gly Cys Leu Gly Val Ser 430 Ser Ala Leu Asn Arg Leu 435 Thr Gly Gly Ser Glu Ser 450 Ilie Arg 465 Gly Gly Met Gly Ile Lys Pro Asn 470 Gly Trp Gly Asp Ph e 460 Met Ala Thr Ala Asp Thr Arg Thr Ser Tyr Thr Met Ala Trp Ala Asp Asp Lys Cys Gly Val1 490 Arg Asp Tyr Pro Tyr Ser 495 Thr Ser Phe Asn Gly Val 515 Thr 500 Glu Asn Pro Leu Asn 505 Tyr Thr Ser Val Asn Thr Met 510 Leu Tyr Glu His Ala Ile Gly Val Trp Ala Thr Val Leu 530 Trp Asn Leu Ile Lys Tyr Gly Lys Asn 540 Asp Gly Ser Arg Val Phe Arg Asn Gly 550 Val Pro Thr Asp Gi y 555 Lys Tyr Leu Met Lys Leu Val Val Asp 565 Gly Met Ala Leu Pro Cys Asn Pro Asn Phe 575 Val. Gin Ala Gly Lys Asn 595 Ar g 580 Asp Ala Ile Leu Asp 585 Ala Asp Ile Val.Leu Thr Gly 590 Arg Gly Leu Arg Cys Giu Ile Trp 600 Arg Gly Phe Ala Gly Gin 610 Gly Ala Ala His Ser 615 Ser Leu Asn Trp Arg Arg Gly Ser Thr 625 Leu Leu Pro Thr Gly Cys 630 <210> 128 186/I282 <211> <212> <213> 394 PRT Aspergilius niger <400> 128 Val Val Phe Ser Lys Thr Ala Ala Leu 10 Val Leu Gly Leu Ser Ser Ala Val Ser Gin Ile Ala Ala Pro Ala Pro Th r Arg Lys Gly Phe Thr Ile Asn Arg Pro Ala Asn Lys Thr Arg Thr Ile Asn Leu Pro Gly Met Tyr Ala Arg Ser Leu Lys Phe Gly Giy Thr Vai Pro Gin Ser Val1 Lys Giu Ala Ala Lys Gly Ser Ala Thr Thr Pro Gin Asn Asn Asp Glu Giu Tyr Leu Thr Pro Val Thr 90 Val Gly Lys Ser Thr Leu His Leu Asp Giu Leu Pro 115 Asp Thr Gly Ser Asp Leu Trp Vai Phe Ser Asp 110 Thr Pro Ser Ser Ser Glu Gin Gly His Asp Leu Ser Ser 130 Ala Thr Lys Leu Gly Tyr Thr Trp Asp 140 Ile Ser Tyr Gly Asp 145 Giy Ser Ser Ala Gly Asp Val Tyr Arg 155 Asp Thr Vai Thr Gly Gly Val Thr Asn Lys Gin Ala Giu Ala Ala Ser Lys Ile 175 Ser Ser Giu Ala Phe Ser 195 Phe Asp Thr 210 Ph e 180 Val Gin Asn Thr Asn Asp Gly Leu Leu Gly Leu 190 Thr Thr Phe Ser Ile Asn Thr Val1 200 Gin Pro Lys Ala Gin 205 Val Lys Ser Gin Leu Asp Ser Pro 215 Leu 220 Phe Ala Val Gin 187 /282 Leu Lys His Asp Ala 225 Ser Lys Tyr Thr Gly 245 Pro 230 Gly Val Tyr Asp Phe 235 Gly Tyr Ile Asp Asp 240 Ser Ile Thr Tyr Asp Ala Asp Ser Ser Gin 255 kn V 00 CIA O 0D rsl Gly Tyr Trp Ser Ser Ser 275 Gly Phe Ser Thr Asp 260 Ser Gly Phe Ser Ala Gly 265 Tyr Ser Ile Gly Asp Gly Ser 270 Thr Thr Leu Ile Ala Asp Thr Ile Leu 290 Leu Asp Asp Glu Ile 295 Val Ser Ala Tyr Tyr 300 Glu Gin Val Ser Gly 305 Ala Gin Glu Ser Glu Ala Gly Gly Val Phe Ser Cys Thr Asn Pro Pro Asp 325 Phe Thr Val Val Gly Asp Tyr Lys Ala Val 335 Val Pro Gly Thr Cys Phe 355 Tyr Ile Asn Tyr Pro Ile Ser Thr Gly Ser Ser 350 Leu Ser Ile Gly Gly Ile Gin Ser 360 Asn Ser Gly Leu Gly 365 Leu Gly 370 Asp Val Phe Leu Ser Gin Tyr Val Val 380 Phe Asn Ser Glu Pro Lys Leu Gly Phe 390 Ala Ala Gin Ala <210> 129 <211> 398 <212> PRT <213> Aspergillus niger <400> 129 Met Lys Ser Ala Ser Leu Leu Thr Ala Ser 1 5 10 Val Leu Leu Gly Cys Ala Ser Ala Glu Val His Lys Leu Lys Leu 25 Asn Lys Val Pro Leu Glu Glu 188/282 Gin Leu Tyr Thr His Asn Ile Asp Ala His Val Arg Ala Leu Gly Gin Lys Tyr Met Gly Ile Arg Pro 55 Ser lie His Lys Glu Leu Val Glu Glu Pro Ile Asn Asp Ser Arg His Asp Leu Val Asp Asn Phe Leu Asn Ala Gin Tyr Phe Ser Glu Ile Leu Gly Thr Pro Pro Gin Lys Phe Lys Ser Ser Glu 115 Val 100 Val Leu Asp Thr Gly 105 Cys Ser Ser Asn Leu Tyr Leu His Asn 125 Trp Val Pro 110 Lys Tyr Asp Cys Ser Ser Ile Ala 120 Ser Ser 130 Ala Ser Ser Thr His Lys Asn Gly Glu Phe Ala Ile Tyr Gly Ser Gly Leu Ser Gly Phe Ser Gin Asp Thr Lys Ile Gly Asp Leu 165 Lys Val Lys Gly Gin 170 Asp Phe Ala Glu Ala Thr 175 Asn Glu Pro Gly Leu Gly 195 Leu Ala Phe Ala Gly Arg Phe Asp Gly Ile Leu 190 Pro Pro Phe Tyr Asp Thr Ile Ser 200 Val Asn Lys Ile Tyr Asn 210 Met Leu Asp Gin Gly 215 Leu Leu Asp Glu Val Phe Ala Phe Tyr 225 Leu Gly Asp Thr Asn 230 Lys Glu Gly Asp Glu 235 Ser Val Ala Thr Gly Gly Val Asp Asp His Tyr Thr Glu Leu Ile Lys Ile Pro 255 Leu Arg Arg Lys 260 Ala Tyr Trp Glu Val 265 Glu Leu Asp Ala Ile Ala Leu 270 189/282 Giy Asp Asp 275 Val Ala Giu Met Giu Asn Thr Gly 280 Pro Ala Asp Leu Val V1 Leu Asp Thr Gly Thr Ser Leu 290 Ala Gin Ile Gly 305 Cys Asp Lys Arg Ile Ala Ala Lys 310 Al a 300 Giu Met Ile Asn Lys Gly Trp Thr Gin Tyr Thr Val Ser 325 Ser Leu Pro Asp Thr Phe Thr Leu Ala Gly 335 His Asn Phe Thr 340 Ile Ser Ser Tyr Asp Tyr Thr Leu Giu 345 Val Gin Gly 350 Pro Val Gly Ser Cys Val 355 Ser Ala Phe Met Gly 360 Met Asp Phe Pro Pro Leu 370 Ala Ile Leu Gly Ala Phe Leu Arg Lys 380 Trp Tyr Ser Val Asp Leu Gly Asn S er 390 Ala Val Gly Leu Lys Ala Lys <210> <211> <212> 130 393 PRT <213> Aspergilius niger <400> 130 Met 1 Arg Lys Tyr Arg 5 Phe His Pro Thr Pro Giy Pro Tyr Thr Leu Ser Ser Ser Gly Gly Arg Ile Gin Gin Thr Gly Pro Tyr Thr Giu Lys Pro Ile Ser Thr Thr Ala His Ilie Arg Gin Leu Val Arg Lys Ser Asp Giu Val Gly Giu Pro Ala Giu Asp Val1Gin Asn Asp Ser Met Tyr Leu Ala Thr Giy Ilie Gly Thr Pro Ala Gin Asn Leu 190/282 Leu Asp Phe Asp Gly Ser Ala Asp Leu Trp Val Trp Ser Asn Lys Leu Pro Ser Thr 100 Leu Leu Ser Giu Asn Lys Thr His Ala 105 Ile Phe Asp 110 Ser Ser Lys 115 Ser Ser Thr Phe Thr Leu Giu Gly Giu Ser Trp Gin 125 Vai Gly Thr Asp Ile Ser 130 Tyr Gly Asp Gly Ser Aia Ser Gly Asp 145 Vai Asn Ile Gly Gi y 150 Val Vai Vai Lys Gin Ala Vai Giu Ala Giu Lys Met Ser 165 Ser Thr Phe Ala Gly Glu Gly Asp Giy Leu 175 Leu Giy Leu Lys Thr Pro 195 Phe Ser Asn Ile Asn 185 Thr Val Gin Pro Lys Ser Val 190 Pro Lys Ser Val Glu Asn Met Leu Gin Asp Asp Ile 205 Ala Giu 210 Leu Phe Thr Ala Leu Asp Thr Trp Arg Asp Thr Asp Asp 220 Asp Leu Val Lys Thr Ser Phe Tyr Thr Ph e 230 Gly Phe Ile Asp Ala Gly Giu Giu Tyr Tyr Thr Pro Asp Asn Ser Gin Gly Phe 255 Trp Leu Phe Arg Ser Giy 275 Asn 260 Ser Thr Ser Ala Thr 265 Val Asn Gly Lys Thr Ile Asn 270 Leu Ala Leu Asn Thr Ala Ilie Asp Thr Gly Thr Val Asp 290 Asp Asp Thr Cys Ala Ile Tyr Ser Ala Ile Asp Gly Ala 300 Pro Thr Asp Thr Ala Tyr 305 Tyr Asp Gin Glu Val1 310 Gin Gly Trp Ile 191 /282 Gin Asp Lys Leu Pro 325 Thr Val Ser Phe Ala Val Gly Glu Lys 330 Gin Phe 335 Val Val Gin Val Tyr Giy 355 Glu Asp Leu Ala Ser Glu Ala Lys Thr Gly Tyr 350 Asp Ile Leu Gly Ile Gin Ser Giy Asp Met Thr 00 Gly Asp 370 Thr Phe Leu Lys Ile Tyr Ala Val Ser 380 Ala Leu Leu Leu Ala 385 Leu Arg Gly Asp Ile 390 Glu Ala His <210> 131 <211> 282 <212> PRT <213> Aspergilius niger <400> 131 Met 1 Lys Phe Ser Thr Ile Leu Thr Gly 5 Leu Phe Ala Thr Ala Ala Leu Ala Ala Ala Ala Gly Leu Thr Giu Lys Arg Ala Arg Lys Glu Ala Arg Gly Ser Asp Lys Arg His Ser Asn Pro Pro Tyr Ile Lys Giu Ile Leu Lys Leu Gly Thr Ser Asn Glu Asp Tyr Ser Ser As n Trp Ala Gly Ala Leu Ile Gly Asp Gly Tyr Thr Lys Val Gly Giu Phe Thr Val1Pro Ser Val Ser Gly Ser Ser Ser Ser Ser Gly Tyr Giy Glu Tyr Cys 115 Gly Tyr Gly Tyr Lys Asn Lys Arg Gin Ser Glu 110 Thr Cys Giu Ala Ser Ala Trp Val1 120 Giy Ile Asp Giy Thr Ala Ile Leu Gin Thr Gly Val Asp Phe Cys Tyr Giu Asp Gly Gin 192/I282 Thr 145 Ser Tyr Asp Ala Tyr Glu Trp Tyr Asp Tyr Ala Tyr Asp 160 Phe Asn Asp Ile Thr 165 Ile Ser Glu Gly Asp 170 Thr Ile Lys Val Thr Val 175 Glu Ala Thr Thr Gly Gin 195 Lys Ser Ser Gly Ala Thr Val Glu Asn Leu Thr 190 Glu Gly Asp Ser Val Thr His Thr 200 Phe Ser Gly Asn Leu Cys 210 Glu Thr Asn Ala Trp Ile Val Glu Asp 220 Phe Glu Ser Gly Asp 225 Ser Leu Val Ala Ala Asp Phe Gly Val Thr Phe Thr Asn 240 Ala Glu Ala Thr Ser 245 Asp Gly Ser Thr Gly Pro Ser Asp Ala Thr 255 Val Met Asp Glu Gin Asp Gly Val Leu Thr Glu Thr Ser Val 270 Ser Gly Asp 275 Ser Val Thr Val Thr Tyr Val 280 <210> 132 <211> 273 <212> PRT <213> Aspergillus niger <400> 132 Met Gly Asp Tyr Gly Pro Gly Val Ser Leu Thr Ala Gin Leu Pro Gly Asn Pro Val Ser Glu Thr Gin Asp Glu Ile Ser Val Leu Val Thr Gly Phe Gly Pro Phe Leu Ile Ala Ser Ser Leu Pro 55 Lys Ser Asn Leu Val Asn Ala Ser Tyr Pro Ser Phe Thr Phe Ser Pro Ala Ser 193/282 Ser Pro Asp Gly Ser Asp Ser Pro Ilie Pro Al a 70 Vai Pro Arg Arg Val Ser Ile Asn Val Arg Thr Thr Val1 Val Ala Tyr Ser Len Pro Val Ile Len Ile Vai Ile 115 Asp Tyr Ala Lys His Gly Giy Arg Arg Pro Asp 110 Tyr Ser Val His Ilie Gly Ilie Ala 120 Ala Met Arg Asn Gin Thr 130 Gin Ala His Arg Gly Tyr Len Met Asp Ile Lys Gly Arg 145 Ser Gly Tyr Gin Asp 150 Gly Giiu Lys Len T rp 155 Arg Gili Len Asp Pro Leu Val Leu Aia Gly Pro Ser Gly His Ala Ser Gin Lys 175 Lys His Leu Lys Thr Phe 195 Pro Arg Pro Pro Gin Asp Phe Len Ala Ala Trp 190 Thr Asp Ala Cys Pro Pro Gin Thr 200 Asp Ala Arg Ile Gly Arg 210 Tyr Len Cys Giu Ile Len Tyr Thr Len Ala Len Ala Tyr 225 Ser Gin Ala Gly Gin Cys Len Asp Gin 245 Arg Asn Val Thr Phe His Val Pro Ala 240 Asp Ilie Gin Thr Gi y 250 Lys Giu Val Ala Val Ala 255 Len Ile Lys Len Val Thr Ser Ser Gin Gin Gin His Ser Val 270 Pro <210> 133 <211> 542 194 /282 <212> PRT <213> Aspergillus niger <400> 133 Met 1 Gly Ser Arg Gin 5 Gly Lys Ala Pro Phe Gly Trp Gly Thr 10 Gin Ser Leu Ala His Asn Leu Asn Phe Gly Ile Asn Pro Leu Gly Leu His Asn Gin Gin Ala Leu Glu Ser Leu Ile Ser Ser Ala Met Ala Thr Glu Tyr Ala Thr Ile Pro Ile Asp His Asn Ala Ser Ala Gly Thr Tyr Gin Asn Arg Trp Val Ser Asp Phe Tyr Gin Pro Asn Pro Ile Phe Tyr Asp Thr Gly Ser Asp Gly Gly Ser Ile Ala Gin Ser Ile Glu Phe 115 Leu Thr Ser Thr Ser Phe Phe Arg Glu Phe Leu 110 Tyr Tyr Gly Asn Ala Met Gly Ala Trp Glu His Arg 125 Asn Ser 130 Thr Pro Ala Pro Val 135 Ser Tyr Glu Thr Pro Glu Ala Trp Gin 145 Ser Tyr Leu Thr Thr Asn Phe Ser Arg 165 Gin Ala Leu Ala Leu Pro Tyr Phe Ala 160 Glu Lys Tyr Pro Asp 170 Met Asp Leu Thr Pro Gin 175 Gly Thr Pro Ile Met Val Gly Ser Tyr Ala Gly Ile Arg Ala 190 Ala Leu Thr 195 Arg Lys Glu Tyr Pro 200 Glu Thr Ile Phe Ala Ala Phe Ser 205 Ser Ser 210 Ser Pro Val Glu Ala 215 Gin Val Asn Met Ser 220 Ala Tyr Tyr Asp 195/282 Gin 225 Val Tyr Arg Gly Met Val 230 Ala Ser Gly Trp Thr 235 Asn Cys Ser Ala 240 Asp Ile H-is Ala Al a 245 Leu Glu Tyr Ile Asp 250 Asp Gin Leu Asp Thr Ala Thr Asn Ser 275 Ser Val Lys Gln Phe Phe Gly Ser Ser Asp Giu 255 Gly Ala Glu 270 Ile Tyr Gly Asn Gly Asp Phe Thr 280 Ala Ala Leu Thr Ala 285 Tyr Phe 290 Gin Ser Tyr Gly Met 295 Ala Gly Gly Ile Gi y 300 Gly Leu Gly Ala Phe 305 Cys Glu Tyr Leu Ile Asp Pro Lys Asn Gly Thr Thr Pro Asp Gly Leu Pro Thr Tyr Gly Gly 330 Gin Tyr Val Ala Glu Arg 335 Trp Ala Ala Thr Asn Cys 355 Trp 340 Pro Thr Phe Leu Glu 345 Leu Val Asn Leu Asn Met Gly 350 Cys Asp Phe Gly Pro Gin Asp Ser Gin Pro Ile Asp 365 Ser Lys 370 Pro Tyr Gly Asp Pro 375 Ser Ala Ile Thr Thr Trp Gin Tyr Ser Giu Trp Gly Phe Gln Ala Asn Asp Gly Pro His Leu Ala Ser Arg Gln Ser Val Glu Gin Gin Glu Val Cys Asn 415 Arg Gin Phe Arg Ala Asp 435 Pro 420 Asp Ala Val Asp Lys 425 Gly Leu Leu Pro Asp Val Asn Gin Phe Gly Gly Trp Thr 445 Pro Ser Pro 430 Ile Arg Pro Arg Ser Leu Ser Asn 450 Val Tyr Phe Ser Gi y 455 Gly Glu Phe Asp Pro Trp 460 196/282 Ser 465 Ile Leu Ser Thr Asp Phe Ala Pro Gly Val Giu Phe Ser Ala Ile Pro Ala 485 Cys Gly Val Gin Thr Asn Glu Asp Thr 490 Val Phe 495 Gly Tyr Val Pro Thr Vai 515 Met 500 Gin Asn Ser Giu His Cys Phe Asp Phe Gin Ala Thr 510 Ala Leu Leu Gly Lys Leu Ser Gly Ile Phe Thr Gin Trp 530 Leu Glu Cys Phe Gin Asn Ser Ser Gin Ser Arg 540 <210> 134 <211> 391 <212> PRT (213> Aspergillus niqer <400> 134 Met Lys Leu Ser Ile Ala Leu Ala Leu Gly Ala Thr Ala Ser Thr Gly Val Leu Ala Asp Pro Pro Ala Val Val Pro Gin Giu Pro Leu Ile Thr Pro Gin Giu Leu Ala Thr His His His Gin Giu Lys Phe Leu Pro Tyr Gin Thr Arq Trp Val Thr Giu Glu Giu 55 Lys Trp Asp Leu Lys Leu Asp Gly Val Asn Phe Ile Asp Ile Thr Glu Arg Asn Thr Phe Tyr Pro Thr Leu His Ala Gly Ser Val His Tyr Pro Pro Thr Met Lys His Asp Asn Met 115 Al a 100 Glu Lys Val Val Leu Leu Arg Gly Leu Ser Lys 110 His Thr Arg Giu Gin Asn Leu Asn 120 Lys Phe Thr Ser Ph e 125 197/282 Tyr Tyr 130 Arg Ser Ser Thr Gly 135 Ile Glu Ser Ala Lys 140 Trp Leu Tyr Ser Val. Ser Asp Val Ile 150 Giu Gin Ser Giy Ala Giu Tyr Gly Thr Val Giu Gin Arg Ilie Pro Giy 180 Ala His Ser Trp Gly 170 Gin Phe Ser Ile Ile Ala 175 Gin Thr Asn Lys Th r 185 Val Vai Leu Gly Asp Ser Ilie 195 Ala His Gin 190 Pro Gly Ala Asn Leu Phe Leu Ser Ile Leu Ala Asp Asp 210 Asp Gly Ser Gly Tb r 215 Val Thr Ile Leu Giu 220 Ala Leu Arg Gly Leu Gin Ser Asp Al a 230 Ile Val Arg Gly Asn 235 Ala Ser Asn Thr Glu Phe His Trp Ser Ala Glu Glu Gly 250 Gly Met Leu Gly Ser Gin 255 Ala Ilie Phe Leu Gin Gin 275 Gin Tyr Lys Arg Lys Arg Asp Ile Lys Ala Met 270 Asp Ala Gly Asp Met Thr Gly Tyr 280 Thr Gin Gly Ala Leu 285 Arq Gin 290 Giu Ala Ile Giy Met Val Asp Tyr Asp Giu Gly Leu Thr 305 Gin Phe Leu Lys Asp 310 Val Thr Thr Giu Cys Gly Ile Gly Ilie Giu Thr Arg Gly Tyr Ala Cys Ser 330 Asp His Thr Ser Ala Ser 335 Lys Tyr Gly Ser Asn Lys 355 Tyr 340 Pro Ala Ala Met Al a 345 Thr Glu Ser Giu Met Giu Asn 350 Arg Tyr Leu Ser 365 Arg Ile His Thr Thr 360 Asp Asp Ser Ile 198 /282 Phe Asp His Met Leu Glu His 370 375 Glu Leu Ala Phe Ala Gin Phe 385 390 <210> 135 <211> 442 <212> PRT <213> Aspergillus niger <400> 135 Ala Arg Leu Thr Leu Gly Phe Ala Tyr 380 Arg Thr Thr Thr Ser Phe Ala Arg Leu Ala Leu Ala Val Val Gly Ile Val Tyr Gly Val Phe Ala Ser Pro Thr 25 Lys Asn Asn Asp Gly Lys Leu Pro Leu His Ser Pro Glu Ser Gly Met Ile Ser Gin Met Val Gin Asn Val Ser 55 Ala Tyr Thr His Ala Ala Asn Tyr Ser Phe Ser Tyr Asp Val His Pro Ile Glu Pro Gly Ser Val Thr Leu Val Ala Leu Asp Gly Val Ile Val Glu Phe Ala Leu Gly Lys Arg Asn Leu Gin Glu Asp 115 Tyr 100 Ala Asp Val Asn Gly 105 Thr Asn Leu Pro Arg Tyr Leu 110 Ser Leu Thr Thr Thr Leu Asp Val Tyr Asp Met Lys Leu 130 Phe Thr Thr Val Ala 135 Ala Leu Arg Glu Leu 140 Asp Ala Gly Arg Ile 145 Ala Leu Asn Val Val Ala Thr Tyr Ile 155 Pro Asp Phe Ala Asn Gly Lys Glu Asn 165 Ile Thr Ile Leu Glu 170 Leu Phe Thr His Thr Ser 175 Gly Phe Ala Ser Asp Pro Ser Pro Pro Leu Phe Ser Ala Tyr Tyr Thr 199/282 185 Thr Tyr Asp 195 Giu Ar Ile Lys Al a 200 Ile Leu Thr Gin Lys 205 Ile Ile Asn Thr Pro 210 Giy Ser Thr Tyr Tyr Leu Asp Leu Phe Met Ser Leu Gly 225 Leu Val Ile Glu Th r 230 Val Thr Gly Arg Al a 235 Leu Asp Asp Leu Ile 240 Tyr Asp Phe Thr Arg 245 Pro Leu Glu Met Ser Thr Phe Phe Asn Arg 255 Gly Asn Ile Ala Val Gin 275 Gly Ser Thr Pro Gin 265 Ser Pro Asn Tyr Asp Arg Thr 270 Giu Pro Gin Giu Phe Gin Ilie Ala Leu Giv Pro Arg Pro 290 Gin Pro Val Arg Gi y 295 Thr Vai His Asp Asn Ala Trp Ser Leu 305 Thr Asp Gly Val Ser Ala Thr Phe Cys 325 His Ala Gly Leu Ser Thr Val Arg Asp 320 Gin Met Ile Leu Asn 330 Asn Gly Thr Tyr Ala Gly 335 Gin Arg Ile Asn Ala Arq 355 Ser Arg Thr Ala Asp Met Ile Phe Thr Asn Phe 350 Giu Leu Asp Phe Pro Gly Asp Al a 360 Arg Ser Leu Gly Gin Tyr 370 Ser Thr Ala Gly Met Ala Ser Leu Thr Ala Ser His Thr 385 Ph e Gly The Thr Gly Trp Leu His Phe 405 Thr 390 Thr Leu Val Met Asp 395 Arg Thr Tyr Asn Ser Asn Arg Val Pro Ser Arg Ala Trp Ser 415 Ser Asn Thr Ile Val Arg Giu Ala Ile Gly Tyr Trp Val Gly Lys Ser 200 /282 Leu Gly Leu Asp Val Ala Phe Ala Leu Leu 435 440 <210> 136 <211> 612 <212> PRT <213> Aspergilius niger <400> 136 Met 1 Ala Ser Trp Leu Ser Thr Leu The Leu Ser Pro Ser Leu Val Ser Ala Ala Pro Giu Lys Ser Ala Ala Asp Tyr Val His Ser Leu Pro Gly Ile Glu Val Gly Pro Leu Leu Lys Met His Ala Gly Asp Pro so Gin Asn Asn Gly Leu Phe Phe Trp His Tyr Gin Asn Arg His Ile Ala Asn Arg Gl n Arg Thr Val Ile Leu Asn Gly Gly Gly Cys Ser Ser Met Asp Gly Ala Leu Met 90 Glu Val Gly Pro Tyr Arg Leu Lys Asp Phe Ala Asn 115 Glu Thr Leu Thr Tyr 105 Asn Glu Gly Ser Trp Asp Giu 110 Gly Phe Ser Leu Leu Phe Val Gin Pro Val Gly Thr 125 Tyr Val 130 Asn Thr Asp Ser Tyr 135 Leu His Giu Leu Glu Met Ser Ala Gin 145 Phe Ile Val Phe Giu Glu Trp Phe Leu Phe Pro Glu Tyr 160 Giu Arg Asp Asp Ile 165 Tyr Ile Ala Gly Giu 170 Ser Tyr Ala Gly Gin His 175 Ile Pro Tvr Ala Lys Ala Ile Giu Arg Asn Lys Asn Val Gin 190 201/I282 Gly Lys Thr 195 Ile Ala Ser Trp Asn 200 Leu Lys Gly Leu Leu 205 Ile Gly Asn Gly Trp 210 Ile Ser Pro Asn Gin Tyr Met Ser Tyr 220 Leu Pro Tyr Ala Tyr 225 Glu Glu Gly Leu Ile 230 Lys Glu Gly Ser Thr Ala Lys Glu Glu Val Leu Gin Val Cys Lys Ser Arg 250 Leu Glu Thr Gly Lys Asn 255 Lys Val His Lys Thr Val 275 Asn Asp Cys Glu Lys Val Met Asn Ala 265 Leu Asn Met Tyr Asp 285 Leu Leu Asp 270 Ile Arg Leu Glu Asp Asn Lys Cys 280 Arg Asp 290 Thr Thr Asp Ala Gly Met Asn Trp Pro 300 Thr Asp Leu Glu Asp 305 Val Lys Pro Tyr Leu 310 Gin Arg Glu Asp Val Lys Ala Leu Ile Asn Pro Glu Lys Ser Gly Trp Val 330 Glu Cys Ser Gly Ala Val 335 Ser Ser Ala Pro Gly Leu 355 Asn Pro Gin Lys Pro Pro Ser Val Gin Leu Leu 350 Ser Gly Asp Leu Glu Ser Gly Gin Ile Leu Leu Lys Asp 370 Leu Ile Cys Asn Val Gly Thr Glu Gin 380 Leu Ile Asn Asn Met 385 Lys Trp Asn Gly Gly 390 Thr Gly Phe Glu Ser Pro Gly Val Ala Pro Arg His Trp Ser Phe Glu Glu Pro Ala Gly Ile Tyr 415 Gin Tyr Ala Arg 420 Asn Leu Thr Tyr Val 425 Leu Ile Tyr Asn Ala Ser His 430 202/282 Met Val Pro 435 Tyr Asp Leu Pro Arg 440 Gin Ser Arg Asp Met 445 Leu Asp Arg Phe Met 450 Asn Val Asp Ile Ser Ile Gly Gly Pro Ala Asp Ser Ile Asp Gly Glu Lys 470 Leu Pro Gin Thr Ser 475 Val Gly Gly His Pro 480 Asn Ser Thr Ala Glu Glu Gin Glu Glu Arg Ile Lys Glu Thr 495 Glu Trp Lys Ile Ile Gly 515 Ala 500 Tyr Ala Lys Ser Gly 505 Glu Ala Val Leu Leu Val Val 510 Ser Arg Arg Val Leu Val Trp Phe Phe Ile Trp Arg His 530 Gin Gly Tyr Arg Gly 535 Val Trp His Lys Asp 540 Met Ser Gly Ser Ser 545 Val Leu Glu Arg His Asn Lys Arg Gly Gly Ala Asp Val 560 Glu Ala Gly Asp Phe 565 Asp Glu Ala Glu Leu 570 Asp Asp Leu His Ser Pro 575 Asp Leu Glu Asp Ile Ser 595 Arg 580 Glu His Tyr Ala Gly Glu Asp Ser Asp Glu Asp 590 Gly Gly Ser Arg Gin His Ser Gin 600 Gin Ala Ser Arg His Asn Leu Ser <210> 137 <211> 531 <212> PRT <213> Aspergillus niger <400> 137 Met Phe Leu Ile Ser Pro Ala Val Thr Val Ala Ala Ala Leu Leu Leu 203/282 Ile Asn Gly Ala Gly Ala Thr Gin Ser Glu Arg Ser Arg 25 Ala Ala Ala Arg Ala Gin His Phe Ser Lys Arg His Pro Tyr Arg Ala Ala Ser Ser Asn Thr Ser Asp Tyr Arg Phe Phe Asn Asn Arg Thr Lys Pro His Leu Val Glu Ser Pro Asp Val His Asp Val Gly Glu Tyr Ser Gly Ser Ile Pro Ile Asp Asp Ser 90 Asn Asn Gly Ser Arg Ser Leu Phe Tyr Thr Ile Tyr 115 Phe Gin Pro Lys Gly Glu Pro Ser Asp Asp Leu 110 Gin Gly Phe Leu Asn Gly Gly Pro 120 Gly Cys Ser Ser Phe Gin 130 Glu Asn Gly Arg Thr Trp Gin Pro Gly 140 Thr Tyr Ala Pro Ile Asn Glu Tyr Ser 150 Trp Val Asn Leu Asn Met Leu Trp Val 160 Asp Gin Pro Val Gly 165 Thr Gly Phe Ser Val 170 Gly Asn Val Thr Ala Thr 175 Asn Glu Glu Glu Asp Leu 195 Ile Ala Ala Asp Leu Asp Phe Phe Glu Lys Phe 190 Thr Gly Glu Tyr Gly Ile Lys Phe Arg Ile Phe Met 205 Ser Tyr 210 Ala Gly Arg Tyr Val 215 Pro Tyr Ile Ser Ala Met Leu Asp Lys 225 Asn Asp Thr Thr Phe Asn Leu Ser Gly 235 Ala Leu Leu Tyr Ala Cys Ile Gly Gin 245 Trp Asp Tyr Ile Ala Glu Leu Pro Ala Tyr 255 204/282 Pro Phe Val Met Asn Glu 275 Lys 260 Gin His Ala Ser Phe Asn Phe Asn Gin Ser Tyr 270 Lys Ala Tyr Leu Glu Thr Thr Glu Glu Cys Gly Tyr 285 Phe Asp 290 Glu Tyr Phe Ala Phe 295 Pro Pro Ser Gly Gin Pro Pro Lys Tyr 305 Met Asn Tyr Ser Cys Asp Ile Tyr Met Ile Tyr Tyr Glu 320 Ala Tyr Asn Pro Asn 325 Pro Cys Phe Asn Pro 330 Tyr Arg Val Ile Asp Glu 335 Cys Pro Leu Glu Pro Ala 355 Leu 340 Trp Asp Val Leu Trp Pro Thr Asp Leu Ala Tyr 350 Lys Lys Ala Pro Thr Thr Tyr Phe 360 Asn Arg Ile Asp Leu His 370 Ala Pro Met Asp Glu Trp Glu Leu Ser Tyr Asp Leu Val 385 Phe Ala Gly Gly Asp 390 Ala Asp Pro Gly Glu Gin Gin Gly Asp 400 Asp Ser Pro Asn Thr Glu Gly Val Leu 410 Pro Arg Val Ile Glu Ala 415 Thr Asn Arg Thr Asn Gly 435 Leu Ile Ala Asn Asp Trp Asp Tyr Leu Ile Ile 430 Asn Gly Gin Thr Leu Leu Ala Ile 440 Gin Asn Met Thr Leu Gly 450 Phe Gin Ser Ala Ala Thr Pro Ile Asp 460 Ile Gin Met Pro Asp 465 Leu Gin Trp Val Glu 470 Ile Phe Glu Ala Glu Gly Tyr Gly Leu Asp Gly Pro Gin 485 Gly Val Met Gly Val 490 Gin His Tyr Glu Arg Gly 495 205 282 Leu Met Trp Ala Glu Thr Tyr Gin Ser 500 505 Gin Gly Arg Val Ser Tyr Arg His Leu 515 520 Gly His Lys Gin Ala Gin Asp 510 Gly Gin Val Gin Trp Leu Leu 525 Giu Ile Leu 530 <c210> 138 <211> 531 <212> PRT <213> Aspergilius niger <400> 138 Leu Phe Arg Ser Leu Leu Ser Thr Val Leu Ala Val Ser Leu Cys Thr Asp Ala Arg Asp As n Ala Ser Ala Ala Lys 25 His Gly Arg Phe Gly Gin Lys Ala Val Lys Ala Met Asn Ile Lys Arg Ser Ala His Ser Leu Lys Ile Pro Giu Asp Tyr Gin Leu Asn Asn Lys Lys Pro Tyr Arg Val Glu Ser Leu Pro Asp Val His Phe Asp Gly Giu Met Tyr Ser Gly Leu Val Pro Giu Lys Gly Asn Val Ser Arg Ser Leu Glu Ile Thr 115 Phe Val Phe Gin Pro 105 Thr Ile Gly Giu Pro Val Asp 110 Ser Leu Giu Ile Trp Leu Asn Gly Pro Gly Cys Ser 125 Ala Phe 130 Leu Gin Glu Asn Val Giu Asn Pro 150 Arg Phe Val Trp Gin 140 Pro Gly Thr Tyr Gin 145 Pro Tyr Ser Trp Val Leu Thr Asn Val Leu 160 206 /282 Trp Val Asp Gin Pro 165 Val Gly Thr Gly Phe 170 Ser Leu Gly Val Pro Thr 175 Ala Thr Ser Asn Trp Gin 195 Giu Glu Ilie Ala Asp Phe Val Lys Phe Phe Lys 190 Tyr Val Thr Gin Ile Phe Giy Ile 200 Lys Asn Phe Lys Ile 205 Giy Giu 210 Ser Tyr Ala Giy Tyr Vai Pro Tyr Ser Ala Ala Phe Leu 225 Asp Gin Asn Asp Thr 230 Giu His Phe Asn Leu 235 Lys Giy Ala Leu Tyr Asp Pro Cys Ile 245 Gly Gin Phe Asp T yr 250 Val Gin Glu Giu Ala Pro 255 Val Val Pro Ser Phe Leu 275 Val Gin Lys Asn Ala Leu Phe Asn Phe Asn Ala 270 Gly Tyr Lys Ala Glu Leu Giu Ser 280 Ile His Glu Gin Cys 285 Asp Phe 290 Ilie Asp Gin Tyr Val Phe Pro Ala Gly Val Gin Pro Pro 305 Val1 Lys Ala Met Asn Asn Asn Ala Val 325 Ser Asp Pro Thr Asp Val Tyr Asp Leu Asp Pro Asn Pro 330 Cys Phe Asn Pro Tyr Glu 335 Ilie Asn Glu Glu Val Asp 355 Cys Pro Ilie Leu Trp 345 Asp Val Leu Gly Phe Pro Thr 350 Asp Arg Ala Tyr Leu Pro Ala Ala Ser Ilie Tyr Ph e 365 Asp Val 370 Lys Arg Ala Met His 375 Ala Pro Asn Ile Trp Ser Glu Cys Val Giu Ser Val Val Gly Gly Asp Gly Pro Glu Gin 207 /282 Giy Asp Tyr Ser Al a 405 Asn Pro Ile Giu Val Leu Pro Gin Val Ile 415 Giu Gly Thr Arg Vai Leu Ile Gi y 425 Asn Gly Asp Tyr Asp Met Val 430 Thr Trp Asn Ile Leu Thr 435 Asn Gly Thr Leu Ser Ile Gin Asn Giy Lys 450 Leu Gly Phe Asp Thr 455 Ala Pro Ser Thr Ile Asn Ile Asp Ile 465 Pro Asp Leu Met Tyr 470 Asn Glu Val Phe Ile 475 Giu Asn Giy Tyr Pro Gin Gly Gly Gly Vai Met Giy Gin His Tyr Giu Arg Giy 495 Leu Met Trp Gin Pro Arg 515 Asp Thr Leu 530 Al a 500 Giu Thr Phe Gin Gly His Met Gin Pro Gin Phe 510 Gly Arg Arg Val Ser Tyr Arg Leu Glu Trp Leu <210> <211> <212> 139 4 92 PRT <213> Aspergilius niger <400> 139 Met 1 Lys Gly Ala Leu Ile Pro Leu Al a 10 Ala Gly Ile Pro Phe Ala His Gly Leu Leu His Lys Arg Gly Pro Ala Vai Val Arg Met Pro Ile Giu Arg Arg Ser Ala Gin Ser Leu Gin Lys Arg Asp Ser Thr Val Gly Val Thr Leu Gin Trp Asp Ala Thr Tyr Tyr Ala Val Asn Leu Thr Leu Gly Thr Pro Ala Gin Lys Val Ser Leu Ala Leu Asp Thr 208/I282 Asn Ser Thr Tyr Gly Ser Ser Asp Leu Trp Val Asn Thr Gly 90 Cys Ser Ile Asp Asn Cys Thr Pro Tyr Leu Tyr Asn Ala Ser Glu Ser 110 Tyr Ala Asp Ser Thr Val 115 Lys Thr Val Gly Th r 120 His Leu Asn Asp Gly Thr 130 Asn Leu Tyr Gly Tyr Val Thr Asp Leu Thr Ile Gly Asn 145 Thr Thr Ile Asp Asn 150 Met Gin Phe Gly Ile 155 Ala Giu Ser Thr Thr 160 Ser Lys Arg Gly Ile 165 Ala Gly Val Gly Lys Ile Ser Thr Tyr Gin 175 Ala Giu His Asp Ser Gly 195 Asp Lys Vai Tyr Al a 185 Asn Leu Pro Gin Ala Leu Val 190 Leu Asp Ser Ala Ile Lys Ser Ala Tyr Ser Ile Leu Giu 210 Ala Ser Thr Gly Ser 215 Leu Leu Phe Gly Gly 220 Val Asn Thr Ala Lys 225 Tyr Lys Gly Asp Gin Thr Leu Pro Ile Pro Val Tyr Lys Tyr Tyr Ser Leu 245 Ala Ile Ala Leu Glu Leu Ser Val Ala Thr 255 Asp Ser Asn Leu Asp Thr 275 Ser Ser Phe Thr Asp 265 Ser Leu Pro Leu Ser Val Ser 270 Leu Val Asn Giy Thr Thr Met Ala Leu Pro Ser Lys Val 290 Tyr Asp Ala Leu As n 295 Ala Thr Tyr Asp Lys 300 Thr Tyr Asp Met Ala Tyr le Asp Cys Asp Thr Arg Giu Ala Asp Tyr Asn Val Thr Tyr 209/I282 305 Ser Phe Ser Gly Al a 325 Thr Ile Thr Val Met Ser Gii Leu Ile Ile 335 Pro Ala Thr Gi u 340 Pro Gly Trp Pro Asp 345 Asn Thr Cys Val 00 Leu Gly Leu 350 Phe Leu Arg Val Pro Ser 355 Gin Pro Giy Vai Leu Leu Giy Asp Ser Aia 370 Tyr Vai Vai Tyr Asp 375 Leu Giu Asn Asn Giu 380 Ile Ser Leu Ala As n 385 Thr Asn Phe Asn Pro 390 Giy Asp Asp Asp Leu Giu Ile Gly Giy Thr Ser Ala Pro Gly Ala Thr Pro 410 Val Pro Ser Ala Val Ser 415 Ser Ala Thr Leu Ser Gly 435 Gly 420 Asn Gly Leu Ile Ser Gly Thr Ala 430 Gly Ser Thr Val Thr Ile Thr Thr Ala Thr Ala Thr 445 Gly Thr 450 Gly Ser Ser Gly Gly 455 Ser Ser Ala Glu Thr Ser Thr Ser Ser 465 Giu Gly Ala Ala Al a 470 Gin Ala Thr Ser Pro Met Asn Leu Leu 480 Pro Gly Leu Ala Ile Gly Leu Leu Leu Ala Leu 490 <210> <211> <212> 140 611 PRT <213> Aspergillus niger <400> 140 Met Leu Ser Ser Leu Leu Ser Gin Gly 1 5 Leu Ser Leu Leu Pro Ser Pro Val Ala 25 Ala Val Ser Leu Ala Val Ala Giu Ile Phe Glu Lys Leu 210/282 Ser Gly Val Pro Asn Gly Trp Tyr Ala Asn Asn Gin Gly Asn Glu Val Ile Arg Leu Gin Ile Ala Leu Gin Gin His Asp Val Ala Gly Phe Glu Gin Ala Val Asp Met Ser Thr Gly His Ala Asp Gly Lys His Phe Arg Thr His Asp Glu Met 90 Lys Arg Met Leu Leu Pro Ser Glu Thr Val His Asn 115 Ala 100 Val Asp Ser Val Asp Trp Leu Glu Ser Ala Gly 110 His Thr Thr Ile Gin Val Asp Ala 120 Asp Trp Val Lys Val Asn 130 Lys Ala Asn Ala Leu Asp Ala Asp Phe 140 Lys Trp Tyr Val Ser 145 Asp Ala Lys His Ile 150 Arg Arg Leu Arg Leu Gin Tyr Ser Pro Asp Ala Leu Val 165 Ser His Ile Asn Met 170 Ile Gin Pro Thr Thr Arg 175 Phe Gly Gin His Ala Asp 195 Gin Pro Asn Arg Thr Met Arg Ser Lys Pro Lys 190 Gin Asn Thr Glu Thr Phe Leu Thr 200 Ala Ala Thr Leu Ser His 210 Cys Asp Ser Ile Thr Pro His Cys Leu 220 Lys Gin Leu Tyr Asn 225 Ile Gly Asp Tyr Gin 230 Ala Asp Pro Lys Gly Ser Lys Ile Phe Ala Ser Tyr Glu Glu Tyr Ala Arg 250 Tyr Ala Asp Leu Glu Arg 255 Phe Glu G]n His 260 Leu Ala Pro Asn Ala 265 Ile Gly Gin Asn Phe Ser Val 270 211 /282 Val Gin Phe 275 Asn Gly Gly Leu Asp Gin Leu Ser Ser 285 Ser Asp Ser Giy Giu 290 Ala Asn Leu Asp Gin Tyr Ile Leu Gly 300 Val Ser Ala Pro Val1 305 Pro Ile Thr Giu Tyr 310 Ser Thr Giy Gly Gly Giu Leu Val Asp Leu Ser Ser Asp Pro Asn Asp Ser Asn Giu Pro Tyr Leu 335 Asp Phe Leu Val Ile Ser 355 Gin 340 Gly Ilie Leu Lys Le u 345 Asn Asn Ser Asp Leu Pro Gin 350 Pro Val Pro Thr Ser Tyr Gly Asp Giu Gin Thr Tyr Ala 370 Arg Thr Val Cys Leu Tyr Aia Gin Gly Ser Arg Giy Val 385 Ser Val Ile Phe Ser Gly Asp Ser Ci y 395 Val Giy Ala Ala Leu Thr Asn Asp Gi y 405 Thr Asn Arg Thr Phe Pro Pro Gin Phe Pro 415 Ala Ser Cys Pro Giu Gin 435 Pro 420 Trp Vai Thr Ser Gly Ala Thr Ser Lys Thr Ser 430 Asp Leu Trp Ala Val Ser Phe Ser 440 Ser Giy Giy Phe Pro Arg 450 Pro Ser Tyr Gin Ala Ala Val Gin Tyr Leu Thr Lys His 465 Leu Gly Asn Lys Ser Giy Leu Phe Ala Ser Gly Arq Al a 480 Phe Pro Asp Vai Ser 485 Aia Gin Gly Val Asn 490 Tyr Aia Val Tyr Asp Lys 495 Giy Met Leu Giy Gin Phe Asp Giy Thr 500 505 Ser Cys Ser Ala Pro Thr Phe 510 212/282 Ser Gly Val Ile Ala Leu Leu Asn Asp Ala Arg 515 520 Leu Arg 525 Ala Gly Leu Pro Val 530 Met Gly Phe Leu Pro Phe Leu Tyr Gi y 540 Val Gly Ser Glu Lys 545 Giy Ala Leu Asn Asp 550 Ile Val Asn Giy Gly 555 Ser Val Giy Cys Gly Arg Asn Arg Ph e 565 Gly Gly Thr Pro Asn 570 Gly Ser Pro Val Phe Ala Ser Asn Ala Thr Thr Trp Asp Pro Val Ser Gly Leu 590 Gly Giu Glu Gly Thr Pro 595 Asp Phe Ala Lys Lys Gly Val Ala Leu 605 Giy Giy Asn 610 <210> 141 <211> 478 <212> PRT <213> Aspergillus niger <400> 141 Met 1 Trp Leu Phe Leu 5 Val Cys Ser Ile Leu Pro Leu Gly Val Val Asn Ala Gin Asn Gly Ser Ser Gin Tyr Phe Asn Asn 25 Lys Thr Lys Giu Phe Val Val Giu Ser Tyr Ala Ile Pro Phe Asp Phe Asp Ile Gly Aia Giy Tyr Leu Pro Asn Thr Pro Ser Giy Ile Ser Leu Tyr Phe Trp Phe Phe Pro Ser Asp Pro Asp Ala Ser Asp Giu Ile Thr Trp Leu Asn Giy Gly Pro Gly Cys Ser Ser Leu Ala Gly Ile Met Leu 213/282 Glu Asn Gly Asn Pro Tyr 115 Pro 100 Phe Leu Trp Gin Pro 105 Gly Thr Tyr Arg Pro Val Arg 110 Ile Asp Gin Ala Trp Asn Asn Thr Asn Met Val Tyr 125 Pro Ala 130 Gly Thr Gly Phe Ser Leu Gly Pro Ser Val Val Ser Glu Phe 145 Asp Val Ala Arg Phe Met Asp Phe Trp 155 Arg Arg Phe Met Lys 160 Thr Phe Asp Leu Asn Arg Lys Ile Leu Thr Gly Glu Ser Tyr 175 Ala Gly Gin Asp Asp Glu 195 Tyr 180 Ile Pro Tyr Ile Ala 185 Ser Gin Met Leu Asp Gin Asp 190 Asp Pro Tyr Tyr Phe Arg Val Gly Ile Gin Ile Asn 205 Ile Asn 210 Glu Leu Pro Val Leu 215 Gin Asp Val Ala Val Asn Gin His Arg 225 Ser Leu Phe Pro Asn Asp Thr Phe Met 235 Ser Gin Ile Thr Lys 240 Leu Ser Asp Asp Gly Tyr Thr Ser Leu Asp Asp Ala Leu Thr 255 Phe Pro Pro Asn Ile Trp 275 Arg 260 Ser Gin Phe Pro Val Pro Tyr Asn Ala Ser Cys 270 Asn Pro Cys Asp Ile Ile Asn Ala Ser Leu Ala Leu 285 Phe Asn 290 Arg Tyr His Ile Pro 295 Asp Ala Cys Pro Thr 300 Pro Trp Asn Pro Val 305 Gly Gly Pro Ile Gly Leu Gly Pro Thr Asn Tyr Phe Asn 315 Arg 320 Ser Asp Val Gin Lys 325 Ala Ile Asn Ala Tyr 330 Pro Thr Asp Tyr Phe Val 335 214/282 00 Cys Lys Asp Pro Ser Ser 355 Gi y 340 Ile Phe Pro Thr Al a 345 Asn Gly Leu Asp Thr Ser Pro 350 Thr Asn Asn Leu Gly Pro Leu Arg Val Ile Glu Thr Ile 370 Ile Ala His Gly Leu 375 Met Asp Phe Giu Leu Leu Ala Gin 380 Gly Lys Gin Gly Gi y Ph e 400 Thr 385 Leu Ile Ser Ile Asn Met Thr Trp As n 395 Giu Arg Giu Pro Glu Pro Leu Phe Pro Tyr Gly Gly Ser Ser 415 Gly Gly Gly Ser Thr Val 435 Vali 420 Leu Gly Thr Ala Thr Giu Arg Gly Leu Thr Phe 430 Ala Pro Giy Phe Ser Ser Gly Giu Ile Pro Giu Ala Ala 450 Tyr Arg Gin Leu Phe Leu Leu Giy Arg 460 Val Ala Asn Leu Ser 465 Thr Ile Ile Glu Gin 470 Val Gin Ile Thr Gin Asn Gly <210> 142 <211> 210 <212> PRT <213> Asperqilius niger <400> 142 Met Ser Lys 1 Ala Thr Thr Lys Tyr Pro Leu Ser Ala Ala Ile Ser 5 Leu Ser Leu Ser Thr Ile Leu Leu Leu Thr Pro Thr Thr Ala Tyr Phe Tyr Thr Asp Ilie Ala Leu Phe Val Lys Asp Thr Asn Cys Ser Phe Ser Leu Val Tyr Pro Ser Leu Gly Asn 55 Cys Asn Gly Gly Tyr 215 /282 Tyr Asp Tyr Ala Gly Ser 70 Phe Gin Met Phe As n 75 Ile Asp Ala Ala Tyr Thr Cys Asn Gly Asp Ser Thr Leu Phe Giu Met Tyr Asn Ser Ser Gly Ser Val Thr Giu 115 Asp 100 Cys Gly Asp Giu Asp Leu Leu Phe Arg Gin Pro 110 Gly Pro Leu Giu Cys Thr Val Asp Val Giu Ser Pro 125 Giu Met 130 Pro Val Trp Phe Giu 135 Leu Gly Ser Leu Gly Asn Cys Gly Gi y 145 Met Ala Gly Thr Met 150 Leu Phe Gly Val Gi y 155 Ile Leu Giu Gly Leu Giu Thr Lys Leu 165 Tyr Trp Lys Cys Tyr 170 Ser Ser Arg Leu Asn Thr 175 Ser Val Thr Ser Val Ser 195 His Arg Leu Ser Ile Leu Ser Met Gly Cys Thr 190 Tyr Tyr Giu Asp Ser Tyr Asn Gi u 200 Leu Aia Ala Ala Asp Leu 210 (210> 143 <211> 608 <212> PRT <213> Aspergilius niger <400> 143 Met Arg His Leu Leu Ser Leu Leu Val Leu 1 5 10 Leu Ile Ala Ser Ala Ala Leu Val Ser Ala Val Pro Ala Gly Ser 25 Ile Ile Thr Pro Gin Pro Pro Val Glu Pro Val His Leu Leu Ser 40 Ser Gin Pro Ser Asp Pro Arg Arg Pro Trp Ile Arg Leu Arg Asp Trp Ile Ile Glu Ser Ile Trp Giy Ile 216/282 00 00 Lys Pro Ala Ser Arg Arg Phe Pro Leu Asn Asp Ser Pro Arg Asn Arg Ser Pro Pro Se r Arg Ilie Leu Ala Arg 90 Tyr Gly Ser Asp Val Val Leu Arg Phe Ala Ala Asp 115 Leu Arg Asn His Giu Ala Glu Ala Leu Ala Gin 110 Pro Ala Phe Ile Leu The Leu Val Trp Ala Ser Thr 125 Val Asp 130 Ile Arg Leu Ala Giu Val Thr Ala Thr Pro Leu Ile Asp 145 Asn Leu Ala Glu Arg 150 Ile Tyr Thr Thr Pro Ser Lys Lys Ile Gly Leu Giu Gly 165 Gin Ser Gly Phe Ser Ser Ser Arg Pro Ala 175 Pro Lys Phe Ile Ilie Pro 195 Asp Leu Phe Phe Giu Tyr Gin Pro Leu Ser Val 190 Ser His Val Trp Met Arg Leu Ala Ser Met Phe Arg Met 210 Ile Ser Val Gly Ser Tyr Giu Gly Giu Ile Pro Ala Arg Leu Ser Ala Gly 230 Ser Ser Thr Ala Ser Gly Pro Arg Thr Ilie Ile Val Thr 245 Gly Giy Ser His Arg Glu Trp Ile Gly Thr 255 Ser Thr Val Ser Lys Ala 275 His Val Met Tyr Thr 265 Leu Ile Thr Lys Tyr Gly Lys 270 Ile Met Ile Val Thr Arq Leu Le u 280 Gin Asp Phe Asp T rp 285 Pro Thr Ile Asn Pro Asp Gly Tyr Val Tyr Thr Trp Glu Thr Asp Arg 217/ 282 Leu 305 Trp Arg Lys Asn Arg 310 Gin Arg Thr Ser Leu 315 Arg Phe Cys Pro Gly 320 Ile Asp Leu Asp Ala Trp Giy Phe Trp Asp Gly Gly Arq Thr 335 00 Arg Ala Asn Gly Met Giu 355 Cys Ser Giu Asn Tyr 345 Ala Giy Asp Giu Pro Phe Giu 350 Glu Thr Gin Ala Gin Gin Leu Gin Trp Ala Leu Asn Asn 3'70 Asn Ala Asp Ile Ser Phe Leu Asp Leu His Ser Tyr 380 Ser Ser Ile Pro Ser Pro Gin Thr Ile Leu Tyr 385 Thr Leu Giu Ser Leu 405 Pro 390 The Ser Tyr Ser Cys 395 400 Ala Ile 415 Giu Glu Leu Gly Gly Leu Ala Lys Arg Tyr Ala Ile Val Thr 435 Th r 420 His Glu Ile Tyr Asp 425 Val Thr Ser Ala Cys Glu Gly 430 Phe Phe Pro Ala Ser Ala Ala Asn Asn Pro Gly Ile Gly 450 Gly Asn Ser Gly Ser Ala Leu Asp T rp 460 Phe Tyr His Gin His Ala Thr Tyr Ser 470 Tyr Gin Ile Lys Arg Asp Arg Gly Tyr Gly Phe Leu Pro Ser Giu His Ile Pro Thr Gly Lys Giu 495 Ile Tyr Asn Ser Phe Asp 515 Val1 500 Val Leu Lys Leu Gi y 505 Ser Phe Leu Ile Gly Gly Asp 510 Ser Lys Asp Val Asp Trp Glu Glu Leu Phe Asp Le u 525 Glu Ser Asp Leu Asp Ser Arg Tyr Ser Lys Ser Asn Asp Arg Ser Pro 218/ 282 Tyr Leu His Asn Ala Asn Gly Pro Leu Pro Asn Ile Asp Glu Asp 560 Asp Asp 575 Glu Asp Lys Glu Trp Val Met Val Glu Glu Asp Tyr Thr Asp Asp Asp Asp Thr Tyr 595 Asp Asp Asp Asp Glu Glu Glu Glu Glu Glu Glu 590 Arg Arg Arg Trp Ala Thr Glu Thr Tyr Glu Phe Arg 605 <210> 144 <211> 416 <212> PRT <213> Aspergillus niger <400> 144 Ala Phe Leu Arg Ile Leu Pro Leu Ala Leu Ile Ala Val Phe Ile Pro Gly Ser Ala Thr Glu Gin Pro His Pro Thr Ile Gin Thr Asp Asn Ala Lys Tyr Ile Val Thr 40 Phe Lys Ser Gly Ile Lys Ile Glu Ser His Ala Ala 55 Trp Val Thr Glu Leu His Arg Arg Ser Pro Ala Gly Ile Glu Gl Gly Arg Ser Thr Glu Asp Asp Arg Thr Tyr Arg Ile Ala Asn Phe Ala Gly 90 Tyr Ala Gly Ser Phe Asp Tyr Val Glu Lys Thr Glu Gin Asp 115 Glu Glu Ile Arg His Asp His Val Gin Val Trp Tyr Leu 120 Asp Thr Leu Val Thr 125 Glu Arg Arg Ala Pro Trp Gly Leu Gly Ser 130 135 Ile Ser His Arg Gly Ser Ser Thr 219/282 Asp 145 Tyr Ile Tyr Asp Asp 150 Ser Ala Gly Glu Gly 155 Thr Tyr Ala Tyr Val Asp Thr Gly Leu Ala Thr His Glu Phe Gly Gly Arg Ala 175 00 Ser Leu Ala His Gly Thr 195 Tyr 180 Asn Ala Ala Gly Gly 185 Glu His Val Asp Asp Val Gly 190 Tyr Gly Val His Val Ala Gly Th r 200 Ile Gly Gly Lys Thr 205 Ser Lys 210 Asn Ala His Leu Ser Val Lys Val Val Gly Glu Ser Ser 225 Ser Thr Ser Val Ile 230 Leu Asp Gly Phe Asn 235 Trp Ala Ala Asri Ile Val Ser Lys Arg Thr Ser Lys Ala Ile Asn Met Ser Leu 255 Gly Gly Gly Asp Glu Gly 275 Tyr 260 Ser Tyr Ala Phe Asn 265 Asn Ala Val Glu Asn Ala Phe 270 Asn Arg Asp Val Leu Ser Cys Ala Ala Gly Asn Ala Ala 290 Arg Thr Ser Pro Ser Ala Pro Asp Ala 300 Ile Thr Val Ala Ile Asn Arg Ser Ala Arg Ala Ser Ser Asn Tyr Gly Val Val Asp Ile Phe 325 Ala Pro Gly Glu Val Leu Ser Ala Trp Thr 335 Gly Ser Asn Pro His Val 355 Ala Thr Asn Thr Ile 345 Ser Gly Thr Ser Met Ala Thr 350 Arg Asp Leu Thr Gly Leu Ile Tyr Leu Met Gly Leu 365 Ala Thr 370 Pro Ala Ala Ala Thr 375 Thr Gl Leu Lys Arg 380 Leu Ala Thr Arg 220/I282 Asn Ala Val Thr Asn Val Ala 385 390 Gly Ser Pro Leu Leu Ala Tyr Giy Asn Ser Giy Val Ser Lys Gly Gly Ser 405 410 Asp Asp Gly Asp Giu Asp 415 <210> 145 <211> 455 <212> PRT <213> Aspergilius niger <400> 145 Met 1 Ile Thr Leu Ser Ala Leu Phe Gly 10 Ser Val Val Tyr Ala Ala Thr Gin Thr Arg Ser Pro Val1Leu Gly Pro Giu Ala Asp Pro Phe Thr Val Phe Glu Gin Asn His Ser Pro Ala Ph e 40 Ser Ile Arg Ile Gin Asp Ser Ile Cys Asp Ala Pro Lys His Leu 70 Ser Pro Gin Phe Gly Trp Leu Asp Ile Gly Phe Phe Trp Tyr Phe 75 Glu Ser Gin Asn Asp Pro Phe His Asp Pro Leu Thr Leu Trp Thr Gly Gly Pro Gly Asp Ser Ser Met Ile 100 Gly Leu Phe Giu Val Gly Pro Cys Arg Ile Asn 110 Thr Lys Asn Giu Phe Gly Asn Gly Thr Asp His 120 Asn Pro Trp Ala Ser Ser 130 Leu Leu Phe Val Gin Pro Val Asp Gly Phe Ser Tyr Asp Giu Gly Tyr Gi u 150 Leu Pro His Asp Ser 155 Arg Glu Ala Ala Asp Met His Arg Phe Leu Arg Leu Phe 165 Ser Giu Ile Phe Pro His 175 221 282 Lys Gin Phe Tyr Ile Pro 195 Le u 180 Pro Val His Leu Ser 185 Gly Giu Ser Tyr Ala Gly Arg 190 Glu Leu Tyr Tyr Leu Ala Thr Ile Leu Giu Gin Lys Asp 210 Ser Pro Arg Ilie Leu Lys Ser Cys Leu 220 Val Gly Asn Gly Met Ser Pro Lys Asp 230 Ala Thr Phe Gly Trp Glu Thr Leu Thr Thr Asn Ser Gly 245 Val Pro Ser Pro Ile 250 Phe Asn Glu Thr Arg Cys 255 Asp Ilie Met Cys Ilie Gin 275 Ala 260 Ala Asn Met Pro His 265 Cys Met Asp Leu 270 Gin Ser Val His Ser Asp Pro Aia 280 Ile Cys His Ala Cys Tyr 290 Asp Ser Val Val Leu Met Aia Lys Leu 300 Leu Leu Arg Met Thr 305 Thr Val Thr Ala Pro 310 Cys Giu Ile Asp Giu 315 Met Cys Tyr Ile Ala Ala Leu Ilie Giu 325 Arg Tyr Leu Asn Pro Ser Val Trp Giu Aia 335 Leu Ser Pro Val Ilie Asp 355 Pro 340 Gin Gin Val Thr Tyr Lys Phe Val Aia Thr Ser 350 Ser Ser Spr Ala Phe Ala Gin Ser 360 Ala Asp Giy Met Lys Gin 370 Ile Ala Phe Leu Aia Asn Asn Val Phe Leu Ala Tyr Gin Gly Asn Leu Asp 385 Ala Asn Ser Leu Ser 405 Leu 390 Ala Cys Asn Thr Al a 395 Giy Asn Leu Arg T rp 400 Trp Lys Gly Gin Giu Phe Thr Ala Lys Pro 415 222/I282 Leu Leu Pro Trp Glu Ile Gin Val Ser 420 425 Thr Ser Arg Phe Ala Phe Val Thr Val 435 440 Val Gly Giu Gly Thr Asp Giu 430 His Leu Leu Asp Asn Ala Gly 445 00 Arq Asp Ser Lys Ile Ser Asn 450 455 (210> i46 (211> 791 <212> PRT <213> Aspergilius niger <400> 146 Arg Phe Leu Tyr Ser Leu Pro Ile Ala Ser Ala Ile Ser Leu Phe Gly Arg His Val Asn Val Gin Ala Ser Gin Ala Pro Ser Ala Ile Pro Ser Gin Ser Thr Leu Asp Gin 40 Pro Thr Ile Lys Thr Arg Val Asp His Leu Asp Phe Asp Ile Thr Asn Ile His Asp Lys His Gin Arg Ile Leu Giu Leu Giu Pro Asn His Asp Ile Ala Giu Asp Ala Ser Val Gin Tyr Leu Ala Asp Gly Asn Val Arg Arg His Giu Ser Leu Leu 115 Pro 100 Ile Ala Pro His Giu 105 His Lys Val Phe Lys Gly Arg 110 Gly Trp Ala Gly Arg Gly Lys Met Trp Asp Pro Arg Ilie 130 Tyr Leu Lys Gin Asp Gly Ser Giu Pro 135 Leu 140 Phe Giu Gly Val Phe 145 Ser Ile Asp Gly Asp 150 Asn His His Val Gin 155 Leu Lys Ser Ala 223/I282 Met Giu Lys Lys Arg Pro Val Asp Val 2.65 Asp 170 Leu Pro Asp Ser Ala Thr 175 Asp Tyr Met Glu Leu Lys 195 Phe Tyr Arg Asp Asp Met Val Arg Leu His Thr 190 Ala Asp Gin Arg Ser Ser Leu Ser Thr Ser Cys Gin 205 Leu Gly 210 Phe Asn Thr Asn Pro 215 Asn His Pro Val Gin Pro Tyr Gly Gin 225 Ala Giu Thr Asp Trp Gly Ala Ile Leu Asn Ser Leu Giy Leu Asn Lys Ar g 245 Gin Ser Asp Ile Gly Ser Val Ser Gly 250 Asn Ala 255 Gly Gly Val Asn 260 Leu Ala Ser Thr Ile Gly Asp Thr Ser 265 Gly Cys Pro 270 Cys Ala Phe Ser Thr Lys 275 Gin Val Ala Leu Gly Val Ala Thr Asp 285 Thr Gly 290 Ser Phe Asn Asn Glu 295 Thr Ala Ala Lys Trp Val Ile Ser Thr 305 Val Asn Ser Ala Asn Val Tyr Glu Ser Phe Asn Ile Ile Gly Leu Arg Leu Thr Ile Thr Ser Ser Cys Pro Asp Asn 335 Pro Pro Ala Thr Ser Arg 355 Al a 340 Thr Ala Trp Asn Met 345 Pro Cys Ser Ser Gly Asn Leu 350 Gin Ser Asp Leu Asp Leu Phe Ser 360 Lys Trp Arg Gly Asp Asn 370 Ala Tyr Trp Thr Met Ser Asp Cys Thr Gly Asn Glu Val1 385 Gly Leu Ser Trp Gly Gin Leu Cys Asn Ser Asp Ala Ser 395 224 /282 Asp Gly Ser Ser Thr Val Ser Gly Thr 405 Asn Val 410 Val Val Arg Ser Ser 415 Gly Ser Asp Ala Val His 435 T rp 420 Gin Ile Phe Ala His Giu Ser Gly His 425 Thr Phe Gly 430 Leu Glu Ala Asp Cys Asp Ser Gin 440 Thr Cys Aia Giu Asp 445 Ser Ser 450 Gin Cys Cys Pro Thr Ser Ser Thr Asn Aia Asn Giy Tyr Ile Met Asn Pro 470 Thr Thr Gly Thr Asp 475 Ile Thr Ala Phe Ser 480 Gin Cys Thr Ile Giy 485 Asn Ile Cys Ala Ala 490 Leu Gly Arg Asn Ser Val 495 Lys Ser Ser Ser Gin Cys 515 Cys 500 Leu Ser Ala Asn Asp Val Thr Thr Tyr Thr Gly 510 Cys Asp Cys Gly Asn Gly Ile Giu Ser Gly Giu Gly Giy 530 Giu Asp Gly Cys Gly 535 Asp Asn Asn Cys Cys 540 Asp Ala Lys Thr Cys 545 Lys Phe Lys Ser Ala Val Cys Asp Ser Asn Asp Ser Cys Ser Ser Cys Gin 565 Phe Ser Ser Ala Gly 570 Thr Val Cys Arq Ala Ser 575 Ser Thr Arg Gly Asp Cys Pro Thr 595 Cys 580 Asp Val Ala Giu Thr 585 Cys Ser Gly Aso Asp Ser Phe Lys Asp Gly Thr Ser Gly Ser Ser Gly Ser 610 Gly Leu Ala Cys Al a 615 Ser Gly Gin Cys Thr 620 Ser Arg Asp Tyr Gin 625 Cys Arg Ser Val Gly Ser Leu Leu Ser Asn Asp Thr 225 /282 Ala Cys Sex Sex Phe 645 Sex Ser Ser Cys Leu Val Cys Thr Ser Pro 655 Lys Ile Gly Pro Cys Gly 675 Cys Tyr Sex Val Asn 665 Gin Asn Phe Leu Asp Giy Thr 670 Lys Gly Gin Sex Gly Gly Tyr Sex Asn Gly Asp Asn Val 690 Glu Sex Trp Ile Lys 695 Asn His Lys Gly Ile 700 Val Ile Gly Val Cys Ala Val Gly Leu Ile Leu Leu Leu Met Thr Cys Ile 720 Val Asn Arg Cys Arg 725 Arg Ala Arg Ala Lys Pro Val Pro Arg Pro 735 Val Pro Tyr Met Asn Gin 755 Pro Trp Pro Gly Ala 745 Arg Pro Pro Pro Pro Pro Pro 750 Asn Giu Pro Trp Pro Ala Arg Tyr Gin Gly Leu Pro Pro 770 Pro Tyr Pro Gly Va1 775 Pro Gly Gin Pro Va1 780 Pro Gin His Met Pro 785 Pro Gin Gly Arg Tyr Ala 790 <210> 147 <211> 481 <212> PRT <213> Aspergillus niger <400> 147 Met Arg Phe Leu Sex Sex Ala Ala Leu Gly Leu Ala Tyr Ala Sex Thr Gin Ala Val Leu Gin Pro Glu Glu 25 His Sex Pro Tyr Sex Pro His His Sex Pro Sex Asp Phe Arg Thr Phe Gin Gin Asn Ile Arg Ile Glu Ser Ile Cys Ala Ala His Sex Ala Gln Tyr Thr Gly Trp Leu Asp 226/282 Ile Giy Arg Lys His Leu Phe Phe Trp Tyr GuSrGnAs Glu Ser Gln Asn Pro Aia Asn Asp Leu Thr Leu Trp Thr Giy Giy Pro Giy Giy Ser Ser Met Giu Tyr Giy 115 Ile 100 Gly Leu Phe Giu Giu 105 Vai Giy Pro Cys Leu Ile Asn Ser Arg Asn Asn Giy Thr Tyr Asn Pro Trp Giy Ser Ser 130 Leu Leu Phe Val Gin Pro Vai Asp Vali 140 Giy Phe Ser Tyr Vali 145 Asp Giu Giy Giu Asp 150 Leu Pro Giy Asp His Gin Ala Ala Asp Met His Arg Phe 165 Leu Gin Leu Phe Vai 170 Ser Giu Val Phe Pro Gin 175 Leu Gin Thr Tyr Val Pro 195 Pro Val His Leu Gly Giu Ser Tyr Aia Giy His 190 Lys Leu Tyr Tyr Leu Giy Ser Ile Val Gin Gin Pro Thr 210 Giu Pro Gin Val Leu 215 Leu His Ser Cys Le u 220 Vai Giy Asn Giy Tyr Ser Pro Arg Asp 230 Thr Thr Tyr Gly Trp Giu Thr Leu Cys 240 Thr Thr Asn Pro Giy 245 Val Pro Giu Pro Val1 250 Phe Asn Arg Thr Arg Cys 255 Asp Ile Met Cys Vai Arg 275 Ala Asn Met Pro Cys Met Giu Val Ser Asp Val 270 Ser Giu Val Asn Pro Asp Pro Ile Cys His Aia Aila 285 Cys Tyr Giu Giy Vai Ile Giy Trp Tyr Asp Asp Giu Ser Gly Giu Giy 227 /282 Arg Asn Arg Phe Asp Ile 310 Thr Ala Pro Ala Leu Asp Gly Ile 320 Cys Tyr Ile Giu Al a 325 Ala Arg Ile Giu Gin 330 Tyr Leu Asn Thr Pro Ala 335 Val Trp Ala Thr Ser Asp 355 Al a 340 Leu Ser Pro Pro Giu Ile Lys Giu Tyr Lys Val 350 Asp Thr Met Asn Vai Ser Arg Phe Asp Leu Thr Thr Pro 370 Ala Ser Giu Gin Ala Phe Leu Leu Asn Gin Vai His Leu Ala Tyr Gin Asn Leu Asp Leu Cys Asn Thr Ala Gi y 400 Asn Leu Arg Trp His Ser Leu Pro Trp 410 Arg Gly Gin Val Giu Phe 415 Ala Ser Lys Lys Gly Gly 435 Leu Arg Pro Trp Trp Val Asp Val Val Ser Gly 430 Phe Ala Leu Vai Ala Gly Thr Lys Giu Glu Ser Val Thr 450 Val Asp Gly Ala His Phe Leu Pro Gin 460 Asp Arg Pro Asp Ile 465 Ala Leu Asp Met Met 470 Val Arg Trp Ile Ser 475 Gly Ala Ser Phe Thr 480 <210> 148 <211> 319 <212> PRT <213> Aspergilius niger <400> 148 Met Thr Leu Leu Leu Asn Phe His Ala Leu 1 5 10 Phe Thr Val Ile Lei) Val 228 /282 Ala Asn Leu Ala An Leu Thr Arg Cys Ser LeLuSrGi Leu Leu Ser Gly Arg Asp Phe Cys Ser Thr Pro Ala Pro Gly Giu Ser Leu Arq Ala Giu His Arg Arg 00 Leu Tyr so Asp Vai Gin Ala Gin Arg Asp Ser Thr Ala Giu Glu Ser Arg Glu 6.5 Val Val Pro Trp Ile Giu Ile Giu Thr Phe His Ile Val Ser Asn Giu Ala Al a Asn Thr Val Ser Asp 90 Asp Met Ile Thr Ser Gin Leu Ser Tyr Leu Giu Gly 115 Le u 100 Gin Lys Ala Tyr Glu 105 Ser Ala Thr Ile Thr Tyr Arg 110 Arg Asn Asp Ile Thr Arg His Asn Asp Ser Trp Asp Giu 130 Leu Gly Met Lys Ala Leu Arg Arg Gi y 140 Asn Tyr Gly Thr Le u 145 Asn Val Tyr Phe Thr Asp Leu Gin Ser Ser Asp Glu Ser Arg Asp Tyr Asn Asp Gly Asn Arg 170 Arg Thr Asp Val Ser Asp 175 Gin Ser Ser Val Asn Ser 195 Thr Vai Leu Gly Cys Thr Leu Pro Asp Pro Ser 190 Gly Cys Asn Ser Ser Pro Arq Ser 200 Ser Tyr Ile Lys Val Leu 210 Ala Asp Ilie Met Gly Gly Ser Leu Al a 220 Gin Tyr Asn Lys Gly 225 Gly Thr Ala Val His 230 Glu Val Gly His Trp 235 Asn Gly Leu Leu Thr Phe Giu Gly Giu 245 Ser Cys Ser Pro Asp 250 Asn Giu Gly Asp Tyr Ile 255 229 /282 Asp Asp Thr Pro 260 Lys Asp Ser Cys 275 Glu Gin Ser Glu Thr Ser Gly Cys Pro Ala Glu 270 His Asn Phe Pro Asp Leu Pro 280 Gly Leu Asp Ala Ile 285 Met Asp Tyr Ser Ser Asp 290 Ala Glu Arg Met Arg Ser 305 310 Asp 295 Cys Tyr Glu Ser Phe 300 Thr Pro Asp Gin Met Trp Ser Ala Arg Glu Gly Lys <210> 149 <211> 639 <212> PRT <213> Aspergillus niger <400> 149 His Val Ser Leu Phe Leu Leu Ser Val 10 Thr Ala Ala Phe Ala Ser Pro Thr Pro Asn Tyr Val Val Glu Arg Arg Asp Ala Leu Pro Leu Leu Pro Ser Val Trp Val Glu Glu Ser Arg 40 Leu Asp Lys Gly Ala Met Arg Ile Gly Leu Thr Gin Ser Asn Leu Asp Gly His Asp Leu Leu Ser Met Glu Val Ser Ser Glu Glu Val His 70 Pro Gin Ser Ser Arg Tyr Gly Lys His His Asp Leu Phe Pro Ser Asn Glu Ala Val Glu Thr Val Ile Ser Gin 115 Thr Trp Ile Glu Ala Gly Ile Ala Pro Ser Arg 110 Ala His Ala Ser Tyr Asn Lys Gin 120 Trp Leu Gin Phe Asp 125 Ser Glu 130 Val Glu Gin Leu Leu Gin Thr Glu Tyr 135 Tyr 140 Ile Tyr Thr His 230/282 Al a 145 Giu Asp Thr Gly Ser Thr Ile Gin Ser 165 Ser 150 His Val Thr Cys GuTy HsVa Glu Tyr His Val His Ie Asp Tyr Ile 170 Thr Pro Giy Val Lys Met 175 00 Leu Giu Vai Ser Leu Giy 195 Arg 180 Gly Thr Pro Ser Lys Arg Asp Ala Giu Lys Arg 190 Ile Asn Ile Ser Leu Pro Pro Ilie 200 Leu Ala Pro Leu Pro 205 Thr Lys 210 Ile Phe Asp Asp Leu Aia His Cys Asp 220 Leu Ala Val Thr Asp Cys Ile Arg Met Tyr Asn Ile Lys Gly Thr Thr Aila 240 Thr Lys Giy Asn Giu 245 Leu Giy Ile Phe Asp Leu Giy Asp Ile Tyr 255 Ser Gin Asp Pro Gin Giy 275 Leu Asn Leu Phe Phe 265 Ala Asn Phe Aia Ser Asp Ile 270 Ala Thr Ala Thr His Pro Thr Leu 280 Asp Ser Ile Asp Gly 285 Pro Thr 290 Asp Val Thr Asn Gly Pro Giu Ser Leu Asp Phe Gin Aia Tyr Pro Ilie Ilie 310 Trp Pro Gin Asn Ile Leu Tyr Gin Asp Asp Pro Asn Giu Asp Asn Tyr Asn Phe Lys Giy Leu 330 Leu Asn 335 Asn Phe Leu Leu Asp Pro 355 Tyr 340 Ala Ile Asp Giy Tyr Cys Asn Giu Thr Ser Ser 350 Ser Ser Pro Gin Tyr Pro Asp Ser Pro Giy Giy Lys Gin 370 Cys Giy Vai Tyr Th r 375 Pro Thr Asn Val Ile 380 Ser Ile Ser Tyr 231 282 Gly 385 Ser Pro Giu Ala Asp 390 Leu Pro Ile Ala Gin Arg Arg Gin His Giu Phe Met Lys 405 Leu Gly Leu Gin Ile Ser Val Val Vai Ala 415 Ser Gly Asp Ala Asp Asn 435 Gly Val Ala Ser Thr Gly Thr Cys Phe Gly Asp 430 Pro Tyr Leu Vai Phe Val Pro Asp 440 Phe Pro Ala Thr Cys 445 Thr Ala 450 Val Gly Gly Thr Leu Pro Leu Gly Asp Ala Ala Lys Asp 465 Gin Giu Ile Ala Val Thr Arg Phe Pro 470 Pro Ser Tyr Gin Asn 490 Se r 475 Gly Gly Gly Phe Ser 480 Asn Ile Tyr Ala Arg 485 His Ser Val Giu Thr Tyr 495 Phe Ser Thr Asn Tyr Thr 515 Thr 500 Ser Asp Asp Leu Thr 505 Tyr Pro Tyr Tyr Ser Gly Val 510 Arg Ile Gly Asp Phe Ser Asn Asp Gly Val Tyr Arg Gly 530 Tyr Pro Asp Val Ser 535 Ala Ile Ala Asp Asn 540 Ile Ile Ile Tyr As n 545 Gin Gly Glu Ala Thr 550 Leu Val Gly Gly Ser Ala Ala Ala Ala Phe Ala Ala Leu Thr Arg Ile As n 570 Giu Giu Arg Leu Ala Lys 575 Gly Lys Ser Giu Ala Phe 595 Thr 580 Val Gly Phe Val Pro Val Leu Tyr Glu His Pro 590 Cys Gly Thr Arg Asp Val Thr Val1 600 Gly Ser Asn Pro Gly 605 Asp Gly 610 Phe Pro Val Ala Ci y 615 Gly Trp Asp Pro Thr Gly Leu Giy 232 /282 Thr Pro Arg Phe Glu Asp Leu Met Asp Ile Phe Val Gly Asp Asp 625 630 635 <210> 150 <211> 371 <212> PRT (213> Aspergillus niger <400> 150 Met 1 Ala Ser Lys Thr 5 Leu Leu Leu Ile Pro 10 Ala Leu Ala Thr Ala Ala Leu Gly Ser Gly Gly Pro Val1Leu Asp Leu Asp Lys Val Asp Leu Gly Thr Pro Thr Leu Trp Phe Asp Leu Met Asp Thr Gly Ser Ser Val Leu Asp Ser Asn Cys T hr Asp Asp Cys Pro Val Ser Gly Tyr Ser Arg His Gly Tyr Leu Thr Ser Thr Gly Val Asn Leu Gly Asn Asp Ser Ile Al a Tyr Ser Gly Gly Val Ser Gly Phe Thr Ala Thr Asp Ile Phe Ala Val 115 Leu 100 Thr Val Pro Asp Asn Val Ser Tyr 110 Ala Asp Gly Ile Thr Asp Ser Trp Ala Ala Leu Phe Ile 130 Gly Leu Ala Ser Ser 135 Thr Ile Ala Phe Asn Thr Thr Thr Al a 145 Val Glu Gin Met Gin Asp Gly Leu Leu 155 Asp Glu Pro Arg Ala Ile Tyr Ala Gly 165 Ser Gly Giu Ser Val Thr Asn Pro Asn Pro 175 Glu Asn Asn Gly 180 Val Phe Thr Phe Gly Ser His Glu Giu Thr Tyr 190 233 /282 Ala Asp Gly 195 Glu Leu Gin Trp Met Lys Met Leu Ser 200 Pro 205 Phe Glu Ile Tyr Lys 210 Thr Asn Leu Leu Gly 215 Ile Gin Gly His Asn Ser Asp Gly Gin 225 Ala Leu Ser Ser Asp 230 Val Leu Asn Trp Tyr 235 Gly Gin Thr Asn Phe Asn Val Ala Gly 245 Ala Ser Ser Ile Ser 250 Ile Pro Asn Asp Gin Ile 255 Glu Ala Met Ala Leu Thr Pro Ser Tyr Ala Asp Ile Ser Ser 270 Ser Ile Ser Gly Tyr Arg 275 Pro Leu Cys Ser Phe Asn Asp Thr Trp 285 Phe Thr 290 Met Gly Phe Tyr Gly 295 Glu Gly Val Thr Asn Leu Thr Gly Asp 305 Gin Leu Ala Val Gly Tyr Gin Asp Asp 315 Asp His Cys Phe Pro 320 Pro Phe Asn Pro Trp 325 Asp Ser Tyr Asn Ile Ile Gly Gin His Trp 335 Leu Ser Asn Thr Tyr Asp 355 Phe 340 Tyr Ala Val Phe Asp 345 Phe Gly Ser Phe Asp Pro Glu 350 Glu Tyr Leu Ile Arg Val Gly Ala Pro Leu Lys Pro Ser Ala 370 <210> 151 <211> 414 <212> PRT <213> Aspergillus niger <400> 151 Met Phe Pro Cys Ser Arg Ile Trp Ser Leu 1 5 10 Leu Val Ala Ala Ala Thr Ala Ser Ala Val Pro Thr Ser Leu Ala Thr Thr His Leu Gin Ser Val 234/282 Asp Leu Leu Leu Thr Arg Ser Ser Tyr Gly Phe Leu Thr Asp Ile Ala Leu Gly Thr Pro Gly Gin Ser 55 Leu Pro Tyr Leu Asp Trp Thr Trp Gly His Tyr Val Val1Thr Thr Leu Cys Tyr Asn Asp Pro Thr Thr Tyr Asp Cys Leu Asn Val Asp Gin Lys 90 Ile Phe Asn Gin Thr Leu Ser Ser Thr Asp Pro Asn 115 Ile Asn Gin Thr Gin Tyr Giy Tyr Leu Tyr Trp 110 ASp Val Ala His Phe Tyr Phe Th r 120 Giu Pro Ala Ala Thr Asp 130 Met Leu Ar Ile Gi y 135 Pro Thr Ala Val Asn 140 Thr Thr Ile Gin Ala Asn Phe Val Asn Giu Thr Ile Ser Ala Phe Pro Phe 155 Ser 160 Gly Val Tyr Gly Ser Pro Val Phe Gin 170 Gly Asp Asn Arg Ser Val 175 Gin Ala Ser Ile Val Ser 195 Tyr Gin Gly Trp Ser Giy Ala Trp His Ser Pro 190 Ala Val Cys Phe Ilie Tyr Cys Asp Asn Ala Thr Lys 205 Ser Gly 210 Tyr ASP Gly Leu Thr Leu Giy Gly Tyr 220 Asn Thr Ser His Gin Gly Asp Ile Trp Tyr Asp Ile Val Thr Giu Ala Ile 240 Asn Thr Leu Asp Phe Vai 245 Tyr Ala Pro Ala Vai Ile Asn 250 Tyr Trp Ala 255 Leu Asn Leu Thr Arg Phe Ser Ile Gly Asp Giu Giu Gin Giu Leu Asn 235/282 265 270 Lys Thr Thr 275 Thr Leu Asp Gly Lys 280 Gin Ala Ala Val Ala 285 Ala Phe Asp His Ala 290 Ser Tyr Gly Arg Gly 295 Ala Pro Val Ser Val 300 Tyr Gly Tyr Gin Arg 305 Leu Val Glu Leu Gly Ala Lys Ala Thr Leu Ser Asp Pro 320 Pro Asn Asn Gly Glu 325 Gin Gly Phe Tyr Phe Asp Cys Arg Asn Ser 335 Ser Leu Leu Trp Glu Ile 355 Pro Leu Arg Tyr Phe Ala Gly Ser Glu Arg Ala 350 Asn Gly Thr Val Pro Glu Asn Tyr 360 Val Glu Val Leu Asn Lys 370 Cys Thr Phe Asn Val 375 Arg Thr Leu Gly Asp 380 Gly Ala Met Val Met 385 Gly Asn Phe Gly Thr Phe Ala Ile Lys Tyr Val Met Asp Phe Glu Lys Leu 405 Gin Val Gly Ile Ala 410 Asp Phe Ala Trp <210> 152 <211> 480 <212> PRT <213> Aspergillus niger <400> 152 Met His Leu Pro Gin 1 5 Arg Leu Val Thr Ala Cys Leu Cys Ala Ser Ala Thr Ala Phe Ile Pro Tyr Thr Ile 25 Lys Leu Asp Thr Ile Ser Ala Arg Asp Ser Leu Ala Arg Arg Phe Leu 40 Pro Ser Asp Asp Val Pro Lys Ser Asp Glu Pro Ser Asp Ala Leu Ala Asp Asp Ser Thr Ser 55 Ser Ala 236/282 Ser Leu Ser Leu Asn Ly AgTi Pr Lys Arg Ile Pro Val Arg Arg Asp Trp Ser Asn Thr Asn Asp Ala Ala Phe Lys Ilie Val Ala Glu Thr Pro Ser Leu Asp Gin Gly Ser Asp 115 Asp 100 Gly Ser Asp Ile Ser 105 Tyr Ile Ser Vai Val Asn Ile 110 Gly Gly Ser Glu Lys Ser Met Met Leu Leu Asp Th r 125 Asp Thr 130 Trp Val Phe Gly Asn Cys Thr Ser Pro Cys Thr Met Asn Thr Phe Gly Ser 150 Asp Asp Ser Ser Thr 155 Leu Glu Met Thr Ser 1 Glu Glu Trp Ser Val1 165 Gly Tyr Gly Thr Ser Val Ser Gly Leu Leu 175 Gly Lys Asp Giy Leu Aia 195 Leu Thr Ile Ala Vai Thr Val Arg Met Thr Phe 190 Pro Met Asp Ser Asn Ala Ser Asp Asn Phe Glu Ser 200 Gly Ile 210 Leu Gly Leu Gly Thr Asn Asp Ser Ser 220 Tyr Asp Asn Pro Th r 225 Phe Met Asp Ala Ala Glu Ser Asn Phe Lys Ser Asn Vai Gly Phe Ala Leu 245 Ser Arg Ser Pro Lys Asp Gly Thr Val Ser 255 Phe Gly Thr Asp Thr Val 275 Tb r 260 Asp Lys Asp Lys Thr Gly Asp Ile Thr Tyr Thr 270 Val Asp Asp Val 285 Gly Ser Asp Ser Tyr 280 Trp Arg Ile Pro Tyr Val 290 Gly Gly Thr Ser Cys Asp 295 Phe Ser Asn Lys Ser Ala Ile Ile 300 237 /282 Asp 305 Thr Gly Thr Ser Ala Met Leu Pro Ser Asp Ser Lys Thr 320 Leu His Ser Leu Ile 325 Pro Gly Ala Lys Ser 330 Ser Gly Ser Tyr His Ile 335 Ile Pro Cys Asn Tyr Thr 355 Thr Thr Thr Lys Gin Val Ala Phe 350 Ser Gly Ser Ile Ser Pro Lys Tyr Val Gly Ala Gly Cys Val Ser 3'70 Trp Leu Leu Gly 385 Tyr Asp Glu Leu Asn Ile Asp Thr 390 Ile 3-75 Ser Tyr Asp Leu Phe 380 Gly Asp Asp Ile Phe Leu Lys Asn Tyr Ala Val Phe Arg 405 Val Giy Phe Ala Giu 410 Arg Ser Ser Asri Thr Thr 415 Ser Ala Ser Thr Thr Thr 435 Asn 420 Ser Thr Ser Ser Gly 425 Thr Ser Ser Thr 430 Ser Ser Ser Gly Ser Ser Thr Thr 440 Thr Thr Ser Ser Ser Ser Ser Asp Ala Glu Gly Ser Ser Met Ile Pro Ala Pro Gin 465 Tyr Phe Phe Ser Ala 470 Leu Ala Ile Ala Ser 475 Phe Met Leu Trp <210> 153 <211> 466 <212> PRT <213> Aspergilius niger <400> 153 Met Thr Ser Ser Thr Leu Arg Leu Ala 1 5 Cys Ser Ser Ala Leu Ser Ser Gin Arg 25 Ala Leu Ala Leu Ser Thr Asp Asp Ser Leu Val Val Pro 238/282 Phe Pro Phe Gly Asn Leu Glu Asp Val His Ile Ala Lys Arg Asp Ser Ser Lys Thr Val Glu Ala Leu Val Ile Tyr Gly Asp Ser Tyr Trp Met Asn Ala Ser Ilie Gly Thr Pro Ala Gin Leu Ser Phe Leu Asp Leu Thr Arg Ser Arg Val Giu Pro Ala 90 Tyr Thr Leu Asp Giu Asn Tyr Giu Cys Pro Thr Asp 115 Ser 100 Asp Asp Giu Leu Ser Giu Phe Gly Phe Tyr Lys 110 Gin Arg His Ser Ser Thr Tyr Gin 120 His Leu Thr Tyr Asp Ala 130 Gly Val Asp Tyr Tyr Leu Asp Thr Ile 140 Thr Leu Gly Asp Ala Thr Asp Asn Pro Leu Asp Met Tyr 155 Leu Leu Ser Tyr Ile 160 Ser Tyr Ser Ser Leu 165 Giy Leu Ser Ser Asn Thr Ser Phe Pro Tyr 175 Ile Leu Val Giy Asp Asn 195 Asp 180 Arg Giy Leu Thr Thr 185 Ser Pro Ser Phe Ser Leu Ile 190 Giy Giy Ile Giy Asn Thr Thr Pro Ser Ile Ile Asn Thr 210 Ser Lys Phe Asn Gi y 215 Pro Leu Gin Ala Ser Phe Ala Asp Ser Ilie Thr Asn Asn 230 Pro Phe Val Thr Giu Ala Asp Ser Gin Leu Thr Thr Asn 245 Thr Asn Asp Asn Ser Thr Tyr Pro Ile 250 Pro Ser 255 Ser Thr Pro Met 260 Met Leu Arg Thr Gi u 265 Giu Leu Ile Thr TFyr Leu Pro 270 239/282 Asn Ser Thr 275 Val Gin Ser Leu Tyr Thr 280 Asp Leu Asn Ile Thr Met Asp Giy Vai 290 Ile Ser Thr Ser Arg 295 Phe Tyr Giy Vai Pro Cys Aia Arg Gin 305 Giu Thr Giu Ser His Thr Ile Ser Leu Ile Giy Asn Met Thr 320 Phe Ser Vai Ser Trp 325 Asp Giu Leu Phe Val1 330 Pro Trp Thr Arg Asp Giy 335 Leu Cys Lys Ala Giu Leu 355 Giy le Gin Aia Gin 345 Asp Ser Asp Tyr Lys Thr Arg 350 Aia Vai Asp Giy Vai Pro Phe Arq Arg Met Tyr Tyr Asn 370 Asn Gin Phe Val Giy 375 Vai Ala Thr Leu Lys 380 Asp Asp Asp Asp Asn Gly Giy Giu Giu Ile Vai Giu Giy Thr Giy Thr Aila 400 Leu Pro Ser Ala Giy Asp Trp Pro Ser Vai Thr Ala Tyr Thr 415 Pro Aia Aia Aia Thr Ser 435 Ser 420 Thr Giy Thr Ala Aia Thr Leu Thr Phe Thr Thr 430 Ser Giu Leu Ser Gly Gly Gly Val 440 Vai Pro Thr Gly Leu 445 Giy Arg 450 Aia Vai 465 Ala Phe Leu Val Gly Val Leu Gly Met 460 Ala Vai Leu Gin <210> 154 <211> 543 <212> PRT <213> Aspergillus niger <400> 154 240/282 Met Met Arg Pro Ile 1 5 Leu Leu Pro Leu Gly Vai Phe Leu Gin Thr Ser Ser Ala Asn Pro Tyr Vai Ser Trp Ser Ser Gin Aia Tyr Giy Pro Asp Giy Pro Trp Gin Al a Vai Ser Ile Asp Val Giy Ser Asn Gin Gin Thr Val Asp Leu Pro Gly Ala Asn Ala Ser Thr Ile Leu Met Ser Thr Leu Thr Asn Lys Thr Ser Ser Thr Cys Tyr Ala Ala Giu Ala Gi y Thr Phe Asn Gin Asn 90 Thr Ser Thr Thr Ala Tyr Thr Thr Ala Ser Gin Giu 115 Ser 100 Ser Trp Giu Thr Tyr Trp Ala Val Giu Giy Gly 110 Ser Phe Val Ala Val Leu Gly Giu Val Thr Leu Gi y 125 Vai Pro 130 Asn Vai Ser Phe Giu 135 Aia Ile Tyr Gin Thr 140 Tyr Gin Thr Tyr Pro 145 Asn Giy Ile Ala Pro Val Ser Val Gi y 155 Ser Leu Ala Leu Gly Pro Tyr Leu Ser 165 Asp Thr Val Ser Ser Thr Vai Leu Asn Met 175 Ilie Aia Gly Gly Met His 195 Trp 180 Leu Tyr Ser Ser Asn 185 Asp Ile Pro Ser Tyr Ser Tyr 190 Ser Leu Ile Ile Gly Ser Val Pro Lys Ile Pro Gi y 205 Leu Giy 210 Giy Tyr Asp Lys Ser 215 Arg Val Ile Gly Asp 220 Val Ser Aia Gin Giy 225 Val Val Ser Ser Ser 230 Gly Leu Leu Glu Leu 235 Giu Leu Lys Asp Ile 240 241 /282 Gly Leu Gly Val Ala Ala Gly Ser Ser Pro Phe Ser Phe Asn Asn Glu 255 Ser Gly Leu Gin Ile Asp 275 Leu Gin Ser Ser Giy 265 Ser Val Gin Ala Lys Thr Val 270 Ala Thr Cys Pro Thr Lys Pro Tyr 280 Met Tyr Leu Pro Gin 285 Asp Ala 290 Ile Thr Ser Thr Met 295 Pro Ile Ser Phe Ser Ser Leu Gly Tyr Phe Trp Asp Thr 310 Thr Ser Asp Asp Leu Asn Ile Thr Ser Ala Ala Tyr Ser Phe Val Phe Met Asn Gly Val Asn Asn 335 Lys Asn Ile Gin Glu Pro 355 Ile Lys Ile Pro Phe 345 Ser Gin Leu Asn Leu Thr Leu 350 Cys Phe Leu Leu Val Asp Gin Asn 360 Val Thr Tyr Phe Pro 365 Thr Thr 370 Ser Thr Pro Val Leu 375 Gly Arg Ala Phe Leu 380 Gin Ser Ala Phe Gly Val Asn Trp Phe 390 Asn Gly Asn Asn Gly Thr Trp Phe Leu 400 Ala Gin Ala Pro Gl y 405 Pro Gly Tyr Ala Glu Asp Ile Thr Arg Ile 415 Ala Val Ser Thr Trp Ala 435 Thr Ser Leu Ser Ser Asn Gly Thr Trp Giu Glu 430 Ser Ser Ser Thr Tyr Trp Gly Lys Thr Ser Asp Ser Lys 450 Ser Gly Leu Ser Ser 455 Gly Ala Lys Ile Gi y 460 Ile Gly Val Gly VJal 465 Gly Val Gly Gly Ala Val 470 Leu Ilie Ala Ala 475 Gly Ile Ala Ile 242/I282 Phe Cys Leu Arg Arg Arg Gly Ala Ser Gin Glu Ala Ala 490 Gly Glu 495 Gin Arg Arg His Ser Glu 515 Ser 500 Met Phe Arg Gly Phe 505 Ala Glu Leu Pro Gly Gly Ala 510 Lys Pro Pro Pro Ala Lys Glu Leu 520 Asp Thr Lys Met His 525 Gin Glu Met Met Ala Ser 530 <210> 155 <211> 844 <212> PRT <213> Aspergillus niger <400> 155 Glu Val Glu Arg Glu Leu Gly Met 1 Arg Leu Thr Gly 5 Gly Val Ala Ala Ala 10 Leu Gly Leu Cys Ala Ala Ala Ser Ala Phe Ala Leu Ser Leu His Pro His Arg 25 Ser Tyr Glu Thr His Asp Tyr Val Ala Gin His Leu Asp Glu Thr Ser Pro Ala Asp Arg Leu Gly Ala Arg His Glu 55 Gly Pro Val Gly Glu Leu Pro Ser His Asp Val His Ala Leu His Thr Phe Ser Ile Leu Asp Gin Leu Arg Arg Glu Asn Ser Asp Arg Arg Arg Arg Arg Arg Ser Gly Asp Asp Ala Ala Gly Ile Leu 115 Val 100 Leu Pro Ser Leu Val 105 Gly Arg Asp Glu Gly Leu Gly 110 Leu His Lys Trp Ser Glu Lys Ala Pro Gin Arg Arg Val 130 Pro Pro Thr Gly Tyr 135 Ala Ala Arg Ser Pro 140 Val Asn Thr Gin Asn Asp Pro Gin Ala Leu Ala Ala Gin Lys Arg Ile Ala Ser Glu Leu 243/282 145 Gly Ile Ala Asp Ile Phe Gly Giu Trp His Leu Tyr Asn Thr 175 Val Gin Leu Gi y 180 His Asp Leu Asn Thr Gly Ile Trp 00 Leu Giu Gly 190 Gly Leu Asp Val Thr Gly 195 Gin Gly Val Thr Thr 200 Ala Ile Val Asp Met Tyr 210 Ser Asn Asp Leu Arg 215 Pro Asn Tyr Phe Ala Gly Ser Tyr Asp 225 Tyr Asn Asp Lys Pro Giu Pro Arg Arg Leu Ser Asp Asp 240 Arg His Gly Thr Arg 245 Cys Ala Gly Giu Ile Gly Ala Ala Lys 250 Asri Asp 255 Val Cys Gly Ile Leu Ser 275 Val1 260 Gly Val Ala Tyr Asp 265 Ser Arg Ile Ala Gly Ile Arg 270 Ala Ile Asn Ala Pro Ile Asp Thr Asp Glu Ala Ala 285 Tyr Ala 290 Tyr Gin Glu Asn Asp 295 Ile Tyr Ser Cys Trp Gly Pro Tyr Asp 305 Asp Gly Ala Thr Giu Ala Pro Gly Thr 315 Leu Ile Lys Arg Met Val Asn Gly Ile 325 Gin Asn Gly Arg Gly Lys Giy Ser Val Phe 335 Val Phe Ala Asp Gly Tyr 355 Al a 340 Gly Asn Gly Ala His Asp Asp Asn Cys Asn Phe 350 Ala Ile Asp Thr Asn Ser Ile Ser Ile Thr Val Arg Glu 370 Gly Asn His Pro Pro 375 Tyr Ser Giu Ser Cys 380 Ser Ala Gin Leu Val Val Ala Tyr Ser Ser Gly Ala Ser Asp Ala Ile His Thr Thr Asp 244 /282 Val Gly Thr Asp Lys 405 Cys Ser Thr Thr His 410 Gly Gly Thr Ser Ala Ala 415 Gly Pro Leu Ala Gly Thr Val Leu Ala Leu Ser Val Arg Pro 430 Ala Ala Val Glu Leu Thr 435 Trp Arg Asp Val Tyr Leu Met Ile Glu 445 Pro Val 450 His Glu Asp Asp Gly 455 Ser Trp Gin Asp Lys Asn Gly Lys Phe Ser His Asp Gly Tyr Gly Lys Val 475 Asp Thr Tyr Thr Val Lys Arg Ala Glu 485 Thr Trp Asp Leu Lys Pro Gin Ala Trp Leu 495 His Ser Pro Gly Leu Ala 515 Trp 500 Gin Arg Val Glu Glu Ile Pro Gin Gly Glu Gin 510 Lys Gly Ala Ser Ser Tyr Glu Thr Glu Asp Met Asn Leu 530 Glu Arg Leu Glu Val Thr Val Thr Met 540 Asn Val Asn His Thr 545 Arg Arg Gly Asp Leu 550 Ser Val Glu Leu Ser Pro Asp Gly Val Ser His Leu Thr Pro Arg Arg Pro 570 Asp Asn Gin Glu Val Gly 575 Tyr Val Asp Ile Gly Lys 595 Trp 580 Thr Phe Met Ser Ala His Trp Gly Glu Ser Gly 590 Asn Glu His Trp Thr Val Ile Lys Asp Thr Asn Val 605 Thr Gly 610 Gin Phe Ile Asp Trp 615 Arg Leu Asn Leu Trp 620 Gly Glu Ala Ile Asp Gly Ala Glu Gin Pro Leu His Pro Met Pro Thr Glu His Asp Asp 245/282 625 625 63560 640 Asp His Ser Tyr Giu Gly Asn Val Thr Thr Ser Ile Ser Ala 655 Val Pro Thr Lys Thr Giu Leu Pro Asp Lys Pro Thr Gly 660 665 Gly Val Asp 670 Thr Gly Ser Arg Pro Val 675 Asn Val Lys Pro Thr Ser Ala Met Leu Thr 690 Glu Pro Ile Asp Asp 695 Glu Giu Leu Gin Lys 700 Tbr Pro Ser Thr Glu 705 Ala Ser Ser Thr Ser Pro Ser Pro Thr Ala Ser Asp Ile Leu Pro Ser Ph e 725 Phe Pro Thr Phe Gly 730 Ala Ser Lys Arq Thr Gin 735 Val Trp Ile Leu Gly Val 755 Ala Ala Ile Gly Ile Ile Val Phe Cys Ile Gly 750 Arg Asp Asp Tyr Phe His Val Gin 760 Arg Arg Lys Arq Ile 765 Ser Arg 770 Asp Asp Tyr Asp Giu Met Ile Glu Giu Asp Giu Leu Gin 785 Leu Ala Met Asn Giy Tyr Asn Ala Phe 805 Ser Asn Arg Ser Arg 795 Arg Arg Gly Giy Giu 800 Ala Gly Giu Ser Giu Giu Pro Leu Phe Ser 815 Asp Giu Asp Giu Pro Tyr Arg Asp 825 Arg Gly Ile Ser Gly Giu Gin 830 Glu Arg Glu 835 Gly Ala Asp Giy His Ser Arg Arg <210> 156 <211> 149 <212> PRT <213> Aspergilius niger 246 /282 <400> 156 Met 1 Lys Thr Phe Ser Thr Val Thr Ser Leu Leu Ala Leu Phe Ser Ser Ala Leu Ala Pro Val Asp Ser Al a Glu Ala Ala Gly Thr Thr Val Ser Leu Thr Ser Val Ser Tyr Asp Thr Ala Asp Val Ser Gly Al a Thr Val Ser Cys Ser Asp Gly Ala Asn Gly Leu Asn Lys Gly Tyr Ser Asn Phe Gly Ser Pro Gly Phe Pro Lys 75 Ile Gly Gly Ala Pro Thr Ile Ala Gly T rp Asn Ser Pro Asn Gly Lys Cys Tyr Ala Leu Thr Tyr Asn Gly Gly Phe 115 Gl y 100 Gin Thr Val Asn Ile 105 Leu Ala Ile Asp Ser Ala Pro 110 Thr Asn Asn Asn Ile Ala Leu Ala Met Asn Thr Gln Ala 130 Gin Gln Leu Gly Ile Glu Ala Thr Tyr 140 Thr Glu Val Asp Val Ser Leu Cys Ala 145 <210> 157 <211> 296 <212> PRT <213> Aspergillus niger <400> 157 Met Ala Gin Ilie Phe Trp Leu Ser Leu Phe 1 5 10 Leu Leu Val Ser Trp Val Arg Ala Giu Ser Asn Arg Thr Glu Val Asp Leu Ile Phe 25 Pro Arg Asn Asp Thr The Aia Pro Met Pro Leu 40 Met Pro Vai Vai Phe Ala Vai Gin 247 /282 Ala Pro Ser Val Ala His Lys Val Asn Thr Asn Giu Thr Val T yr Ile 75 Giu Tyr Gly Tyr Tyr Pro Val Gly Arg Pro 70 Gly Gin Thr Asp His Val Ser Asp Ser Asn Giu Thr Thr Phe Ser Val Ser Gly Ile Giy Arg Thr Arg Trp Thr 115 Phe 100 Asn Thr Thr Gly Ser 105 Trp Giu Leu Phe Trp Arg Leu 110 Tyr Asn Gin Asn Cys Ser Ile Giu Asp Ser Arg Ser Tyr 130 Pro Trp Ile Ser Ser 135 Pro Tyr Ile Asp Gi y 140 Ser Leu Asn lie Asp 145 Lys Vai Tyr Giu Phe His Tyr Thr Tyr Asn Vai Ile Val1 160 Asp Arg Vai Thr Phe 165 Ser Thr Arg Giu Asp 170 Ala Ser Gin Pro Asn Leu 175 Thr Thr Leu Leu Leu Ser 195 Thr 180 Asn Ser Giu Asn Asp Lys Val Ser Ser Leu Aia 190 Leu Pro Gin Ile Vai Asp Ser Leu 200 Arg Ile Pro Pro Giu Asp 210 Ile Asp Thr Val Met Cys Pro Gin Leu 220 Aia Asp Ala Arg Asn Ser Thr Ser Th r 230 Ser Ser Pro Cys Val Ser Ile Ser Pro 240 Giu Vai Giu Ser Ile Leu Ala Lys Ile 250 Ala Asp Asn Glu Cys Asn 255 Asn Ala Leu Gly Ser Aia 275 His 260 Pro Ala Val Ser Thr Thr Giu Giu Thr Lys Giu 270 Leu Val Ile Ser Ser His Asp His 280 Gly His Ala Val T rp 285 248/282 Thr Leu Ala Phe Ala Phe Leu Phe 290 295 <210> <211> <212> <213> 158 310 PRT Aspergilius niger <400> 158 Met 1 Gly Gly Arg Asp 5 Val Ala Ile Leu Arg His Phe Ala Val Thr Ser Ser Gin Val Thr Ser Ser Vai Asn Gly Val Ser Gly Met Phe Gin His Thr Lys Lys Lys Ser Pro Ser Phe Thr Thr Asn Gin Phe Phe Thr Ala Ala Ile Ala Ala Ile Phe Ala Ser Vai Ala Val Ala Ala Pro Gin Arg Gly Leu Giu Ala Arg Leu Ala Arg Giy Ser Lys Gly Ser Arg Pro Leu Gin Ala Val Arg Pro Ala Ser Thr Lys Asn Gin Thr Vai Giu Pro 115 Val Glu Tyr Ser Asn Trp Ser Gly Ala Val Leu 110 Thr Giy Thr Pro Ser Ala Ala Thr Tyr Thr Ala Phe Thr 130 Val Pro Giu Pro Thr 135 Gly Asn Ser Gly Ser Gin Ala Ala Ser Ala Trp Val Gly 145 Gin Thr Gly Val Asp 165 Asp Gly Asp Thr Gly Asn Ala Ile Phe Thr Val Thr Gly Giu Ala Ser Phe Asp 175 Ala Trp Tyr Giu 180 Trp Tyr Pro Asp Ala Tyr Asp Phe Ser Gly Ile 190 249 /282 Asp Ile Ser 195 Ala Gly Asp Glu Val Ala Ile Val Glu 205 Ser Tyr Thr Ser Thr 210 Thr Gly Ilie Ala Ile 215 Ile Glu Asn Lys Thr Gly Gin Lys Val 225 Ser Lys Glu Leu Ser Ser Ser Ser Leu 235 Gly Gly Gin Asn Al a 240 Glu Trp Ile Val Glu 245 Asp Phe Giu Glu Gly Ser Leu Val Asn Leu 255 Val Asp Phe Gly Gly Glu 275 Gi y 260 Thr Val Thr Phe Thr 265 Gly Ala Vai Ala Lys Ala Ala 270 Giu Ile Giu Ser Val Gly Leu Asp Ala Thr Ile Ile 285 Glu Asn 290 Gly Gin Val Val Thr 295 Asp Val Thr Ile Ser Asp Ser Glu Val1 305 Thr Ile Thr Tyr <210> 159 (211> 681 <212> PRT (213> Aspergililus niger <400> 159 Arg Cys Ser Leu Ile Ser Leu Leu Gi y 10 Leu Ala Ala Ile Pro Ala Leu Gly Gly Met Vai Lys Cys Pro Phe Ala His Ala Asn Met Gly Ile Asp Asn Ala Ser Lys Ala His Ala His Ser Arg Pro Leu Ser Ser Pro Ser Thr Val Pro 55 Thr Ser Ser Ser Thr Pro Ser Val Gly Gin Lys Gly Val Phe Met 7n Met Asn Arg Ile Ala 75 Pro Gly Thr Ser Giu Leu Tyr Ile Ala Asn Thr Asp Gly Ser Asn Glu Arg Pro Leu Leu Ser 250 /282 Asn Pro Val Ile Thr Phe 115 Tyr 100 Giu Tyr His Ala Phe Ser Pro Asp Val Giu Trp 110 Asp Ile Tyr Thr Ser Giu Arg Asn 120 Giy Asp Gly Asn Arg Val 130 Arg Thr Asn Gly Ser 135 Asp Leu Gin Giu Leu 140 Vai Ala Thr Pro Vai Giu Asp Ser Vai Ile Ser Pro Gly Arg Leu Aia Tyr Vai Ser Thr Aila 165 Asn Asn Met Lys Ala 170 Asn Ile Trp Ile Leu Asp 175 Leu Gin Thr Ala Asn Ser 195 Giy 180 Aia Gin Trp Asn Leu 185 Thr Asn Thr Pro Thr Thr Ala 190 Trp Ser Pro Ser Leu Met Giu Tyr Leu Arg Pro Asp Giy 210 Giu Trp Ile Aia Ph e 215 Ser Ser Asp Arg Asn 220 Thr Gin Trp Asp Gly 225 His Giy Vai Pro Th r 230 Phe Leu Giy Arg Giy Trp Glu Thr Gin Giu Leu Ser Le u 245 Tyr Aia Ile Arg Pro 250 Asn Giy Ser Asp Phe Arg 255 Gin Ile Ile Ala Asp Giy 275 Lys Pro Tyr Tyr Ser 265 Leu Giy Ser Pro Lys Trp Ser 270 Giu Asp Thr Lys Arg Ie Val Tyr Giu Met Thr Tyr Asn 290 Aia His Arg Pro Giu 295 Thr Ile Thr Thr Al a 300 Asn Ser Thr Ile Met Ser Vai Asp Phe 305 Giu 310 Thr Gly Thr Asp Val1 315 Arg Val Giu Val Al a 320 Gly Ser Gly Val Lys Gin Phe Pro Gin Tyr Leu Asp Lys Asn Gly Thr 251 /282 Ile Ala Tyr Ala Gly Leu 355 Leu Lys Gly Gly Ser Giu Gly Phe Tyr Thr Thr 350 Ser Pro Ala Tyr Val Asn Thr Thr 360 Ser Ala Thr Leu Arg 365 Trp Ser 370 Pro Asp Gly Lys Val Val Tyr Glu Ser Thr Trp Ser Ile 385 Arg Ser Gly Tyr Gin Leu Tyr Ser Trp 395 Asp Ser Asp Trp Asp 400 Tyr Arg Phe Thr Asp 405 Val Phe Pro Gin Ser His Gin Giu Arg Val 415 Aia Ile Thr Thr Thr Gly 435 Gin 420 Lys Gin Leu Gly Ser Ser Ile Val Thr Leu Asn 430 Thr Ala Asp Gly Asp Leu Gin Val Tyr Asp Pro Ser 445 Phe Val 450 Ser Asp Asp Giu Thr 455 Thr Gly Leu Ser Tyr Gin Pro Ser Trp 465 Ser Pro Cys Gly Giu 470 Trp Leu Val Phe Gi y 475 Vai Gly Phe Trp Giu Thr Arg Giu Ser Gly Gly Trp Vai Arg Ala Thr Ala Asn 495 Giy Ser Tyr Asp Giy Ala 515 Ser 500 Glu Vai Leu Val Asn 505 Ser Ser Tyr Ser Ile Thr Giu 510 Asp Giy Lys Leu Asn Ser Giy Pro Ser Phe Ser Lys Val 530 Val Tyr Arg Val Trp 535 Gly Ala Asp Thr Aila 540 Thr Tyr Gly Asn Al a 545 Ser Glu Ile Giy Le u 550 Arg Val Leu Asp Leu Glu Thr Arg Lys 555 Thr Val Leu Thr Thr Giu Trp Asp Asn Leu Pro Gin Phe Ser Pro Asp 252 /282 575 Gly Glu Leu Val Cys Thr 595 Len Phe Thr Arg Thr Ser Thr Tyr Asn Tyr Asp 590 Len Thr Ser Ile Arg Pro Asp Thr Asp Leu Arg Va1 605 Ser Gly 610 Ala Asn Asp Ala His 615 Ala Val Trp Ser Gin 620 Asp Gly Arg Ile Met 625 Trp Ser Thr Gly Tyr Gly Phe Arq Glu Cys Ala Leu Gly Asp Thr Phe Gin 645 Pro Tyr Gly Gin Val 650 Met Ile Met Asp Ala Asp 655 Gly Gly Asn Pro Leu Phe 675 <210> 160 <211> 624 <212> PRT Lys Leu Met Thr Ser Met Trp Glu Asp Ser Met 670 Leu Pro Arg Glu Val Leu 680 <213> Aspergillus niger <400> 160 Met 1 Pro Pro Asp Lys Ser Pro Gly Tyr 10 Gin Pro Gly Met Ala Val Leu Pro Ser Arg Pro His Pro Ala Gly Lys Ala Ile Arq Phe Leu Len Ser Leu Ala Leu Val Ala Ala Ile Val Gin Leu Cys Gly Asn Phe His Lys Asn Arg Ser Val Glu Gin Gin Len Ser Gin Thr Leu Asp Asp Glu Ser Phe Trp Glu Asp Val Pro Thr Lys Gin Vai Tyr His Pro Phe Gly Asp His Glu Cys Ala Arg Leu Ser Len 253/282 Pro Met Asn Ala Val Ile 115 Trp 100 Asn Arg Thr Asp Giu Giy Ser Lys Ile Ala Leo 110 Ala Arg Tyr Lys Leu Pro Ala Lys 120 Val Pro Val Thr Asp 125 Gly Gly 130 Ala Ile Leu Leu Pro Gly Gly Pro Gly Ser Gly Val Ser 145 Met Val Phe Arg Tyr 150 Gly Lys Ala Ile Gin 155 Thr Ile Val Asp Ser 160 Pro Glu Ser Pro Ala Asp Ser Aia Gly Lys Tyr Phe Asp Vai 175 Val Ser Phe Cys Phe Pro 195 Asp 180 Pro Arg Gly Val Asn Thr Thr Pro Asn Phe Ser 190 Gin Ser Glu Asp Pro Ala Thr Arg 200 Lys Ala Trp Leo Ala Glu 210 Gly Leu Leu Giy Ser Giu Giy Vai Asp Thr Arg Trp Arg Tyr Glu Ala Phe 230 Glu Arg Leo Leu Ser 235 Thr Ala Pro Asn Phe Pro Val Gly Asn Val Asp Ala Giu 250 Arg Ile Arg Leo His Asn 255 Arg Trp Lys Gly Thr Ilie 275 Lys 260 Gly Gbu Glu Lys Leo Tyr Trp Gly Phe Ser Tyr 270 His Arg Ile Leo Gly Ser Thr Phe 280 Ala Ala Met Gin Pro 285 Asn Arg 290 Ala Val Ile Asp Gly 295 Val Cys Asn Ala Asp Tyr Tyr Ala Asn Trp Leo Thr Leo Gin Asp Ser Ala Ala Phe Asn Phe Phe Glu Tyr Cys 325 Tyr Thr Ala Gly Pro 330 Ser Ala Cys Pro Phe Ala 335 254/I282 Leu Giy Giy Thr Asn Leu 355 Pro Giu Asp Leu Ser Arg Tyr Giu Gin Ile Leu 350 Giy Asn Arg Thr Ser Ser Pro Ala Val Ser Pro Gly Pro 370 Glu Ile Ilie Thr Ser Asp Val Lys Leu Vai Vai Gin Aila 385 Leu Tyr Vai Pro Leu 390 Lys Leu Phe Asp Leu 395 Vai Aia Arg Leu Aia Giu Leu Giu Giy Asn Giy Ser Phe Ala Asp Leu Lys Tyr 415 Giu Ala Lys Gin Tyr Lys 435 Gin 420 Trp Pro Vai Pro Pro 425 Pro Cys Asp Ser Ser Ser Thr 430 Arg Asn Ile Vai Pro Gly Giu Asp Gin Giu Ala Giy 445 Leu Cys 450 Thr Asp Giy Pro Gi y 455 Leu Asp Gly Thr Lys Giu Asp Phe Arg 465 Phe Ser Tyr Trp Asn Trp Aia Giu Val 485 Leu Arq Gly Gin Lys Ala Val Gly Asp 480 Arg Met Ser Cys Lys Leu Giu Thr Arg Pro 495 Giu Trp Arg Thr Ser His 515 Asp Giy Met Arq Gin Gly Pro Phe Ala Giy Asn 510 Pro Val Thr Pro Leu Leu Phe Gly Asn Thr Tyr Pro Leu 530 Arg Asn Ala His Thr Met Ala Arg Gly 535 Pro Giu Ser Ile Val1 545 Leu Giu Gin Asn Val Giy His Cys Thr Leu Ser Gly 555 Phe Gin Thr Gly Pro Leu Cys Thr Ala Ala Ile Arg Gin Giu Leu 575 255/I282 Pro Asp Pro Gly Thr Val Cys Gin 580 Ala Giy Tyr Giu Arg Ser Gin Val 595 600 Met Ser Ala Leu His Ser Leu Ser 610 615 Val Glu Giu Leu Pro Phe Arg Leu 590 Thr Giu Leu Met Ser Pro Glu Phe Arg Gly Asp 605 Leu Leu Gly Ala <210> 161 <211> 554 <212> PRT <213> Aspergilius niger <400> 161 Met Leu Ser Ser Leu Leu Leu Gly Gly Leu Leu Gly Leu Ala Thr Ala Gin Phe Pro His Giu Asn Pro Glu Pro Glu Gly Thr Val Leu Lys Ser Lys Leu Cys Glu Thr Val Thr Ilie Ser Ph e Lys Glu Pro Gly Thr Pro Gly Val Arg Ser Ser Gly Tyr Val Leu Pro Pro Ala Ser Thr Ser Phe Phe Phe Phe Glu Ala Arg 75 Lys Asp Pro Ser Asn Ala Pro Leu Ala Trp Leu Asn Gly Pro Gly Giy Ser Ser Leu Met Gly Leu Lys Thr Thr 115 Leu 100 Giu Giu Leu Gly Cys Ser Ile Ala Ser Asp Ser 110 Vai Asn Leu Val Leu Asn Pro Ser Trp Asn Asn Leu Phe 130 Leu Asp Gin Pro Thr Gin Vai Gly Phe Ser Tyr Asp Val Pro Thr 145 Asn Gly Thr Leu Thr 150 Ala Asn Gly Thr Al a 155 Phe Ala Ala His 256/I282 Leu Trp His Phe Ala Gin Thr Trp Phe Gl Ph Pr Hi Glu Phe Pro His Tyr Lys 175 Pro Asn Asp Tyr Gly Pro 195 Asp 180 Arg Val Ser Leu Trp 185 Ala Giu Ser Tyr Gly Gly His 190 Asp Lys Ile Gly Ile Phe Arg Phe Gin Gin Gin Ala Glu 210 Gly Thr Ala Giu Asp Gly Ala Gin Tyr 215 Leu 220 His Leu Asp Thr Leu 225 Gly Ile Val Asn Leu Met Asp Met Val1 235 Ile Gin Glu Giu Tyr Ilie Thr Trp Pro 245 Tyr Asn Asn Vai Leu Ala Pro Ser Ser Phe 255 Asn Ser Arg Lys Giu Arq 275 Giy 260 Phe Arg Asp Gin Al a 265 Leu Ala Cys Giu Aia Ala Leu 270 Ile Ser Glu Asp Ser Giy Leu Pro 280 His Ser Gly Lys Ile Cys 290 Gly Gly Leu Ala Giu Trp Gly Asp Gly Pro Ile Thr Tyr 300 Ala His Pro Lys Asn His Thr Phe Asn Gly Trp Tyr Asp Asp Pro Phe Pro Al a 325 Lys His Met Leu Gly 330 Tyr Leu Thr Gin Glu Ser 335 Val Leu Ala Ala Val Ala 355 Leu Gly Val Pro Asn Phe Thr Ser Ser Ser Ser 350 His Gly Gly Thr Gin Phe Ilie Lys 360 Thr Phe Asp Ile Val1 365 Phe Leu 370 Asp Ala Ile Gly Tyr Gly Asp Arg 390 Leu Leu Asp Ser Val Lys Val His Met 385 Met Asp Tyr Ala Cys Asn 395 Trp Val Gly Gly 257/282 I 00 00 Lys Ala Ser Leu Al a 405 Val Pro Tyr Ser Ar g 410 Ile Thr Glu Phe Ala Asp 415 Thr Gly Tyr Ser 420 Pro Leu Leu Thr Asp Gly Ile Ser Gly Met Thr 430 Arg Gln Leu 435 Gly Asn Tyr Ser Phe 440 Thr Arg Val Phe Gln Ala Gly His Glu Val 450 Pro Ser Tyr Gln Val Ala Ala Tyr Glu 460 Ile Phe Met Arg Ala 465 Thr Phe Asn Lys Asp 470 Ile Pro Thr Gly Leu Ala Val Asp Glu Phe Gln Ser Val Gly Pro Lys Asp 485 Thr 490 Trp His Ile Lys Asn Ile 495 Pro Pro Ile Cys Thr Pro 515 Pro Lys Pro Gln Tyr Val Leu Ser Pro Gly Thr 510 Ala Thr Val Glu Val Trp Glu Thr 520 Val Leu Asn Gly Lys Asp 530 Trp Tyr Val Val Asp Ser Ala Gly Val1 540 Glu Asp His Glu Gly P 545 <210> <211> <212> he Ser Ile Leu Gly 550 Gly Asp Glu Leu 162 578 PRT <213> Aspergillus niger <400> 162 Met Thr Arg Phe Gln Leu Leu Pro Leu 1 5 Ser Ile Ala Ala Leu Ser Ile Pro Ser 25 Ala Gly Leu Leu Ala Pro Pro Gln Gln Ile Leu Asp Ser Leu Thr Phe Gly Glu His Thr Asp 40 Gly Phe Cys Pro Leu Ala Pro Lys 258 /282 Val Giu Val Pro Asp Asp Phe Phe Pro Ala Lys Phe Val Glu Asp Ala Ser Phe Lys Arg Gin Val Asn Arg Leu Ser Arg Ala Gin Val Pro Thr Al a Ile Asp Asp Tyr Met 90 Lys Asp Pro Tyr Asp Glu Lys Phe Ala Pro Leu Thr 115 Phe Leu Asp Phe Lys Leu Leu Gin Thr Leu Phe 110 Arq Phe Giy His Ser Tyr Ala Arg 120 Val Asp His Ile Asn 125 Leu Val 130 Phe Thr Leu Asri Thr Asp Asp Ser Lys Pro Leu Leu Thr Ala His Gin Asp 150 Val Val Pro Ile Asn 155 Asp Pro Ala Asp Trp 160 Thr Tyr Pro Pro Asp Gly His Tyr Gly Glu Trp Leu Trp Gly 175 Arq Gly Ala Val Glu Asp 195 Ser 180 Asp Cys Lys Asn Val 185 Leu Ile Giy Leu Met Ser Val 190 Thr Val Val Leu Leu Ser Gin Trp Glu Pro Thr Arg 205 Leu Ala 210 Phe Gly Phe Asp Giu Ser His Gly Leu Gly Ala Gly Ile Ala Lys Phe Glu Lys Lys Tyr Gi y 235 Pro Asp Ser Phe Glu 240 Phe Ile Leu Asp Giu 245 Gly Gly Met Gly Giu Val Leu Asp Asp Asn 255 Asn Asn Giv Ile Asp Vai 275 Val1 260 Val Tyr Ala Leu Pro 265 Gly Val Gly Glu Lys Gly Ser 270 Ser Ser Val Val Leu Thr Leu Ala 280 Val Pro Gly Gly His 285 259 /282 Pro Pro 290 Pro His Thr Gly Gly Ile Ile Ala Glu 300 Ile Ile Tyr Glu Glu Arg Gin Asp Leu 310 Phe Val Pro Val Asp Thr His His Pro 320 Thr Arg Lys Met Leu 325 Glu Cys Gin Val His Ser Pro Ser Gin Val 335 Glu Pro Trp Ala Glu Lys 355 Ala Ser Ala Leu Gin Ser Ser Asp Tyr Ile Ser Leu 350 Phe Ile Leu Leu Ala Ser Ser Gly Asp Lys Phe Arg 365 Gin Thr 370 Ser Gin Ala Ala Asp 375 Ile Ile Asn Gly Val Lys Ser Asn Leu Pro Glu Lys Asn Ala Leu Val Asn 395 Tyr Arg Ile Ala Leu 400 His Gin Thr Pro Asp 405 Asp Ile Lys Asn Ala Val Glu Ile Ile Ser 415 Pro Ile Val Asp Thr Val 435 Lys 420 Lys Tyr Asn Leu Leu Thr Ala Phe Pro Glu Ser 430 Thr Thr Leu Asp Pro Ser Leu Asn His Leu Thr Leu 445 Ser Gly 450 Ala Leu Ser Pro Ala 455 Pro Val Ser Pro Asp Ile Asp Thr Asp 465 Ala Val Trp Ala Phe Ser Gly Val Thr 475 Arg Ser Val Phe Glu 480 Ser Val Pro Ser Glu Gly Arg Lys Val Val Ser Gly Asp Ile 495 Met Thr Gly Ile Tyr Arg 515 Asn 500 Thr Asp Thr Arg Tyr Trp Ala Leu Ser Arg Asn 510 Asn Ile His Trp Ser Pro Ser Ala Gly Lys Ala Leu 525 260/282 Thr Val Asp 530 Giu Arg Ile Ile Asp Ile His Leu 540 Giu Ala Met Met Leu Tyr Tyr Asp Leu Ile 545 550 Arg Ser Phe Asp Arg Thr Asp Ser Val Ile Ser Ala Al a 565 Ser Ala Ala Ala Asp 570 Asp Glu Leu Ala His Asp 575 Val Leu <210> 163 <211> 456 <212> PRT <213> Aspergillus niger <400> 163 Met Lys Ser Thr Thr Leu Leu Ser Leu Trp Ala Ala Gin Ser Ala Tyr Ser Leu Asn Phe Glu Ile His Glu Arg Asp Giu Pro Ala Thr Leu Gin Phe Lys Arg Ser Arg Arg Gin Ile Al a 40 Asp Arg Ser Arg Arg Thr Ala Ser Aia Asp Leu Asn Leu Ala Thr Asn Leu Gly Tyr Thr Met Asn Leu Thr Leu Gly Thr Pro Gly Gin Val Ser Val Thr Asp Thr Gly Ser Ser Asp Leu Trp Val Asn Gly Ala Asn Ser Ser Vai Cys Pro Cys Tyr Thr Phe 115 Asp Tyr Gly Ser Asn Ser Ser Ala Ser Ser Thr 110 Asp Gly Ser Val Asn Asp Giu Ph e 120 Tyr Ile Gin Tyr Glu Ala 130 Thr Gly Asp Tyr Val Asn 135 Asp Thr Leu Lys 140 Phe Ser Asn Val Thr Leu Thr Asn Phe Gin Phe Ala Val Ala Tyr Asp Gly Asp Ser Giu 261 282 Giu Gly Val Leu Gly 165 Ile Gly Tyr Ala Se r 170 Asn Glu Ala Ser Gin Ala 175 Thr Val Gly Giy Glu Tyr Thr Phe Pro Glu Aia 00 Leu Val Asp 190 Asp Asp Leu Gin Gly Ala 195 Ilie Asn Trp Pro Tyr Ser Leu Trp Asp Glu 210 Gly Lys Gly Thr Ile 215 Leu Phe Gly Gly Val 220 Asn Thr Ala Lys Tyr 225 Tyr Gly Ser Leu Gin 230 Thr Leu Pro Ile Ser Ile Glu Asp Tyr Val Glu Phe Val Asn Leu Thr Val His Leu Glu Lys Asn 255 Giy Asn Ser Val Ser Val Asn Asn Ser 260 265 Ala Thr Gin Phe Pro Ile Pro 270 Thr Ser Ala Ala Val Leu 275 Asp Ser Gly Thr Leu Thr Tyr Ile Pro 285 Ala Ala 290 Ser Ilie Tyr Giu Val Gly Ala Gin Tyr 300 Leu Ser Glu Tyr Gly 305 Tyr Gly Val Ilie Giu 310 Cys Asp Val Lys Asp 315 Giu Asp Phe Thr Ph e 320 Leu Phe Asp Phe Gb y 325 Ser Phe Asn Met Val Asp Ile Ser Glu Met 335 Ile Leu Glu Gly Leu Ala 355 Al a 340 Ser Ser Asp Met Asp Met Asn Val Cys Thr Phe 350 Thr Phe Leu Val Ile Glu Asn Ala Leu Leu Gly Asp 365 Arg Ser 370 Ala Tyr Val Val Tyr 375 Asp Leu Gly Asn As n 380 Giu Ile Ser Leu Ala Lys Ala Asn Phe Asn Pro Gly Glu Asp His Val Leu Glu Ile Gly 262/282 385 Thr Gly Ser Asp Ala 405 Val Pro Lys Ala Gly Ala Thr Ala Thr Gly 415 Ala Ala Ala Ser Ala Thr 435 Ser Thr Ala Ser Asp Lys Ser Asp Lys Glu Ser 430 Ala Gly Val Val Pro Arg Ser Gin 440 Ile Val Ser Leu Leu Val 450 Gly Val Phe Leu Val Leu 455 <210> 164 <211> 664 <212> PRT <213> Aspergillus niger <400> 164 Met Leu Val Arg Gin Leu Ala Leu Ala 1 5 Leu 10 Ala Ile Ala Ala Leu Ser Asp Ala Ile Lys Pro Ala Pro Thr Ser Ile Lys Val Leu His Glu Lys Arg His Ser Asp Ala Ser Asp Trp Val Gly Ala Arg Val Glu Val Leu Pro Met Arg Ile Leu Ala Gin Asn Leu Asp Lys Gly Asp Phe Leu Met Glu Val Ser Asp Pro Lys Ser Ser Lys Tyr Gin Tyr Trp Ser Ala Asp Glu Val His Asp 90 Ile Phe Ser Pro Ser Glu Glu Ala Val Pro Ser Arg 115 Glu 100 Ala Val Arg Glu Leu Val Ala Ser Gly Ile His 110 Ala Phe Asp Val Val His Ser Asp 120 Asn Lys Gly Trp Leu 125 Ala Tyr 130 Ala His Glu Ala Glu 135 Arg Leu Phe Met Thr 140 Glu Phe His Glu 263/282 His 145 Glu Ser Asp Arg Ser Ala 150 Lys Ile Arg Gly Cys Asp Gin Tyr 160 His Val Pro Glu His 165 Ile Gin Lys His Asp Tyr Ile Thr Pro Gly 175 Val Lys Leu Ser Gin Leu 195 Thr 180 Gin Val Val Lys Arg 185 Thr Asn Lys Val Lys Arg Ala 190 Gin Gly Pro Ala His Ser Ser Lys 200 Ala Lys Ser Ala Ala 205 Gin Pro 210 Leu Pro Asn Lys Ala 215 Lys Phe Leu Pro Asp Leu Arg Gly Cys 225 Gly Tyr Asn Ile Pro Ser Cys Ile Lys 235 Ala Leu Tyr Gin Pro Asp Ala Lys Thr 245 Ala Thr Pro Asn Asn 250 Ser Leu Gly Leu Tyr Glu 255 Gin Gly Asp Tyr Ala Pro 275 Tyr 260 Phe Ala Lys Ser Leu Asp Leu Phe Tyr Lys Glu 270 Ala Leu Ile Trp Val Pro Gin Gly 280 Thr Tyr Pro lie Asp Gly 290 Ala Asn Tyr Ser Val 295 Pro Ser Tyr Ser Ser 300 Leu Asn Thr Gly Glu 305 Ser Asp Ile Asp Asp Met Ala Tyr Leu Leu Tyr Pro Gin 320 Gin Val Thr Leu Gin Val Asp Asp Leu Tyr Glu Pro Val Glu 335 Val Asp Thr Ser Tyr Cys 355 Thr 340 Asn Leu Phe Asn Thr 345 Phe Leu Asp Ala Leu Asp Gly 350 Asp Pro Ser Thr Tyr Ser Ala Tyr 360 Gly Glu Thr Gly Asp 365 Ile Asp 370 Pro Val Tyr Pro Asp 375 Thr Arg Pro Gly Gly 380 Tyr Lys Gly Lys 264/282 Gin Cys Gly Val Lys Pro Thr Asn Val1 395 Ile Ser Ala Ser Gly Gin Ser Glu Ala 405 Asp Leu Pro Val Tyr Thr Lys Arg Gin Cys 415 Asn Giu Phe Ser Gly Asp 435 Met 420 Lys Leu Gly Leu Gin 425 Gly His Ser Ilie Leu Phe Ala 430 Asp Glu Asn Tyr Gly Val Ala Phe Ala Gly Asp Gly Cys 450 Leu Gly Pro Giu Lys Ile Phe Asn Gin Tyr Pro Ser Asn 465 Cys Pro Tyr Val Thr 470 Ser Val Giy Giy Thr 475 Met Leu Tyr Gly Gin Thr Val Asn Asp 485 Ser Glu Ser Val His Val Asn Leu Gly Gly 495 Thr Ala Ser Gin Pro Ala 515 Asn 500 Phe Ser Thr Ser Gly Phe Ser Asn Tyr Phe Pro 510 Gin Ser Ala Tyr Gin Phe Ala Al a 520 Val Glu Gin Tyr Asn Leu 530 Ser Tyr Pro Tyr Tyr 535 Ser Glu Phe Giu Asp Val Asn Thr Lys Gly Leu Tyr Arg Leu Gly Arg Tyr Pro Asp Val Ser 560 Ala Asn Gly Ala Phe Arg Ala Tyr Asp Gly Tyr Asp Tyr His 575 Trp Tyr Gly Ser 580 Ser Leu Ala Ser Pro 585 Leu Phe Ala Ser Val Leu Thr 590 Leu Leu Asn 595 Giu Glu Arg Phe Ilie Gly Lys Giy Pro Val Gly Phe 605 Val Asn 610 Pro Val Leu Tyr Tyr Pro Gin Val Leu 620 Asn Asp Ile Thr 265 /282 Asn Giy Thr Asn Ala Gly Cys 625 630 Gly Trp Asp Pro Ala Ser Gly 645 Gly Thr Tyr Leu Gly Thr 650 Phe Ser Ala Ile Pro Asn Tyr Pro Leu Met 655 00 Lys Gin Leu Phe Leu Ser Len Pro 660 <210> 165 <211> 520 <212> PRT <213> Aspergilins niger <400> 165 Met 1 Arg Val Thr Thr Ala Ile Ala Ser 5 Leu 10 Len Len Vai Giy Ser Ala Thr Ser Len His Arg Ser Gin Asn Pro His Arg Arg 25 Ala Val Pro Pro Pro Len Ser Arg Thr Thr Val Ala Ser Arg Val Pro Val Gin Arg Asp Phe Gin Tyr Len Thr Lys Thr Ala Arq Phe Len Val Asn Gly Ser Ile Pro Gin Val1Asp Phe Asp Val Gly -75 Gin Ser Tyr Ala Gly Len Leu Pro Asn Th r Pro Thr Gly Asn Ser Len Phe Phe Trp Phe Phe Pro Ser Asn Pro Gin Ala Ser Asp Gin Ile Thr Ile Trp Len Asn Gly Gly 115 Pro Gly Cys Ser Len Asp Gly Leu Len 125 Gin Gin Asn Gly Pro 130 Phe Len Trp Gin Pro 135 Gly Thr Tyr Lys Val Pro Asn Pro Tyr 145 Ser Trp Thr Asn Len 150 Thr Asn Val Val Ile Asp Gin Pro 266 /282 Gly Thr Gly Phe Se r 165 Pro Gly Pro Ser Thr 170 Val Asn Asn Giu Giu Asp 175 Val Ala Ala Asp Leu His 195 Phe Asn Ser Trp Lys His Phe Val Asp Thr Phe 190 Tyr Ala Gly Gly Arg Lys Vai Ile Thr Gly Giu Ser 205 Met Tyr 210 Val Pro Tyr Ile Ala 215 Asp Ala Met Leu Glu Giu Asp Thr Thr 225 Tyr Phe Asn Leu Gly Ile Gin Ile Asp Pro Ser Ile Ser Asp Ser Val Met 245 Met Tyr Ser Pro Al a 250 Val Arg His Leu Asn His 255 Tyr Asn Asn Ala Lys Ala 275 Phe Gin Leu Asn Ser 265 Thr Phe Leu Ser Tyr Ile Asn 270 Lys Ala Ile Asp Lys Cys Gly Asn Ala Phe Leu Asp 285 Thr Tyr 290 Pro Pro Pro Ser Phe Pro Thr Ala Pro 300 Giu Ile Thr Giu Asp Cys Gin Val Trp 305 Pro Cys Phe Asn Tyr 325 Asp 310 Giu Val Val Met Ala Tyr Asp Ilie Tyr His Leu Ile Phe Cys Pro Tyr Leu Trp 335 Asp Val Leu Asn Arg Ser 355 Gly 340 Phe Pro Ser Leu Ser Gly Pro Asn Asn Tyr Phe 350 Thr Asp Tyr Asp Val Gin Lys Ile 360 Leu His Val Pro Ser Val 370 Cys Ser Giu Thr Ile Phe Ala Asn Asp Gly Ser Asp Ser Ser Trp Gly Leu Pro Ser Val Ile 395 Giu Arg Thr Asn 267/I282 Thr Ile Ile Gly His Gly Trp Leu Asp Tyr 410 Leu Leu Phe Leu Asn Gly Ser Leu Ala Gin Arg Pro 435 Thr 420 Ile Gin Asn Met Thr 425 Trp Asn Gly Lys Gin Gly Phe 430 Tyr Gly Leu Pro Val Giu Pro Phe Val Pro Tyr His 445 Ala Giu 450 Leu Tyr Trp Gly Giu Pro Asp Pro Tyr 460 Arg Asn Leu Asp Ala Gly Leu Thr Phe 480 Ala Gly Tyr Leu Gi y 470 Thr Ala His Thr Ser Ser Val Tyr Leu Ser Gly His Giu 485 Pro Gin Tyr Val Pro Gly 495 Ala Ala Tyr Gin Leu Glu Phe Leu Gly Arg Ile Ser Ser Leu 510 Ser Ala Lys 515 <210> 166 <211> 551 <212> PRT Gly Asn Tyr Thr <213> Aspergillus niger <400> 166 Met 1 Arg Gly Ser Arg 5 Leu Val Leu Leu Pro Leu Ala Ala Leu Ser Cys Ala Met Pro Lys Ala Pro Glu Asn Glu Trp Ser Thr Ile Arg Arg Gin Leu Asn Asn Val Ser Thr Gly Val Ser Ile Lys Thr Pro Thr Ilie Arg Tyr Lys Giu Pro Gly Thr Glu Gly 55 Ile Cys Glu Thr Thr Gly Vai Lys Ser Tyr Ser Gly Tyr Val Leu Ser Pro Giu 268 /282 His Thr Phe Phe Trp Phe Phe Gin Ser Arg Arg Asp Pro Glu Asn Asp Pro Val Thr Len Trp Len Asn 100 Gin Gin Len Gly Gly Gly 105 Pro Gly Ser Asp Ser Leu Ile 110 Gly Leu Phe 115 00 Pro 120 Cys H-is Ile Thr Pro 125 Glu Tyr Gin Ser Ile 130 Ile Asn Gin Tyr Trp Asn Gin Vai Thr Asn Len Len Phe Len 145 Ser Gin Pro Leu Gi y 150 Vai Gly Phe Ser Ser Giu Thr Gin Giy Ser Len Asn Pro 165 Phe Thr Gly Ala Gin Asn Ala Ser Phe Ala 175 Gly Vai Gin Thr Asp Ile 195 Giy 180 Arg Tyr Pro Val Asp Ala Thr Ile Ile Asp Thr 190 Gly Phe Len Ala Ala Arg Ala Thr 200 Trp Giu Val Leu Gin 205 Ser Gly 210 Len Ser Gin Len Asp 215 Ser Glu Val Lys Ser 220 Lys Giu Phe Asn Leu 225 His Trp Thr Gin Ser Phe Tyr Gin Gin 245 Giy Gly His Tyr Gi y 235 Pro Ala Phe Phe Asn Ser Lys Ile Al a 250 Ser Giy Giu Vai Asn Gly 255 Val Gin Len Ala Ala Ilie 275 Phe Asn Ser Len Ile Ile Asn Gly Ile Ile Asp 270 Asn Asn Thr Gin Ala Asp Tyr Ala Asp Phe Ala Tyr Gly 290 Ile Lys Ala Val Asn 295 Asp Thr Vai Tyr Asn 300 Tyr Met Lys Phe Ala 305 Asn Thr Met Pro Asn 310 Gly Cys Gin Asp Gin Val Ala Ser Cys Lys 315 320 269 /282 Leu Thr Asn Arg Ser Leu Ser Asp Ala lie Cys Thr Giu Ala 335 Ala Asn Met Gly Arq Gly 355 Cys 340 Arg Asp Asn Val Giu 345 Gly Pro Tyr Tyr Gin Phe Giy 350 Pro Thr Pro Val Tyr Asp Ile Arg 360 His Pro Tyr Asn Pro Ser 370 Tyr Phe Val Asp Leu Lys Lys Asp Ser 380 Val Met Asp Ala Gly Val Asp Ile Asn 390 Tyr Thr Glu Ser Ser 395 Gly Glu Val Tyr Ala Phe Gin Gin Gly Asp Phe Val Pro Asn Phe Ile Glu Asp 415 Leu Glu Glu Asp Aia Asp 435 Leu Gin Leu Pro Arg Vai Ser Leu Ile Tyr Gly 430 Ile Ser Leu Tyr Ile Cys Asn Trp 440 Phe Gly Giy Gin Ala Val 450 Asn Tyr Pro His Al a 455 Ala Gin Phe Arg Ala Gly Tyr Thr Pro 465 Met Thr Val Asp Vai Giu Tyr Giy Thr Arg Giu Tyr Gly 480 Asn Phe Ser Phe Thr 485 Arg Val Tyr Gin Ala 490 Giy His Giu Val Pro Tyr 495 Tyr Gin Pro Trp Asp Ilie 515 Ile 500 Ala Ala Leu Gin Leu 505 Phe Asn Arg Thr Leu Phe Gly 510 Tyr Ser Thr Aia Ala Gly Thr Gin Ile Trp Pro Glu 525 Asn Giy 530 Thr Ser Gin Ala His Thr Giu Ser Phe Val Pro Leu Ser 540 Thr 545 Ala Ser Ser Thr Val Asn 550 270 /282 <210> <211> <212> 13> 167 623 PRT Aspergillus niger <400> 167 Met 1 Pro Phe Pro Ph e 5 Ser Ser Ala Leu Gly Tyr Ile Leu Thr Thr Ser Thr Thr Pro Giu Asp Leu Thr Ser Leu Val Gly Gin Tyr Tyr Pro Pro Thr Gly Ala Arg Leu Thr Val Ile His Ser Giu Ile Phe Ilie Ser Tyr Lys Gin Pro Gly Ile Cys Thr Thr Pro Ser Thr Pro Ser Tyr Ser Gly Ilie His Leu Pro Pro 75 His Thr Leu Thr Asn Leu Ser Ile Pro Gly Ile Ser Ilie Ser Pro Tyr Pro Ile Asn Thr Phe Phe Trp Pro Leu Thr 115 Phe Pro Ser Arq His His Asn Asn Asp Thr Ser 110 Ser Met Ile Ile Trp Met Asn Gly 120 Gly Pro Gly Giy Gly Leu 130 Phe Gin Giu Asn Gly 135 Pro Cys Thr Vai Thr Asp Ser Asn Ser 145 Thr Ala Tyr Asn Trp Ser Trp Asn Giu 155 Tyr Vai Asp Met Leu 160 Tyr Ilie Giu Gin Pro 165 Val Gin Thr Giy Ph e 170 Ser Tyr Asp Val Leu Arg 175 Asn Giy Thr Ser Gin Asp 195 Leu 180 Asp Leu Asn Giu Phe Leu Vai Gly Thr Leu Pro 190 Gly Gly Arg Val His Giy Thr Asn Gly Thr Val Asn 205 Aia Leu Trp Val Ala Leu Gin Vai Trp Leu Gly Giu Phe Ser Giu Tyr 271 282 Ser Ser Vai Asp Gly 230 Asn Gly Gly Giy Asp 235 Asp Arg Val Ser Trp Thr Giu Ser Gly Gly Arg Tyr Pro Ala Tyr Thr Ala Leu 255 Phe Gin Giu Lys Lys Ile 275 Met 260 Asn Giu Arg Ilie Glu 265 Ser Giy Glu Val Ser Thr Gly 270 Cys Val Asp His Leu Asp Thr Gly Ile Ile Asn Leu Leu 290 Val Gin Val Pro Ser 295 Phe Pro Giu Gin Aila 300 Tyr Asn Asn Thr Giy Ilie Glu Gly Ile 310 Asn Arg Thr Leu Tyr 315 Asp Arg Ala Met Asp 320 Ser Trp Ser Lys Pro 325 Gly Gly Cys Arg Asp 330 Met Ile Ile Glu Cys Arg 335 Asp Ala Giy Asp Tyr Cys 355 Leu Giy Asp Pro Ile Ile Cys Glu Giu Ala Ser 350 Thr Ser Gly Ser Arg Giu Ilie Ser Leu Tyr Thr Asn 365 Arg Giy 370 Tyr Tyr Asp Ile Ala 375 His Phe Thr Pro Ala Ala Leu Val Tyr Phe Val Giy Leu Asn Arg Pro Val Gin Lys Ala Gly Vai Pro Val Tyr Thr Met Ser Giu Ala Vai Gly Asn Ser 415 Phe Ala Ser Gly Asp Ilie 435 Thr 420 Gly Asp Tyr Pro Arg 425 Asn Asp Pro Arg Gly Met Ile 430 Ala Met Val Gly Tyr Leu Leu Asp 440 Ser Gly Val Lys Tyr Gly Asp Arg Asp Tyr Ala Cys Pro Trp Arg Gly Gly Glu Asp Val 272/I282 Leu Leu Val Giu Tyr 470 Glu Asp Ala Giu Phe Arg Ala Ala Tyr Ala Giu Val Gin 485 Thr Lys Ser Ser Tyr 490 Val Gly Gly Leu Val Arg 495 Gin Tyr Gly Val Pro Phe 515 The Ser Phe Thr Arg 505 Vai Phe Gin Ala Gly His Glu 510 Asn Arg Ala Tyr Gin Pro Giu Ala Tyr Glu Ile Gin Phe 530 Asn Trp Asp Ile Al a 535 Thr Gly Gly Ile Ser 540 Leu Glu Gin Asn Gin 545 Ser Tyr Gly Thr Giy Pro Ser Ser Trp His Ile Lys Glu Val Pro Glu Ser 565 Pro Giu Pro Thr Cys 570 Tyr Leu Leu Ala Met Asp 575 Ser Thr Cys Vai Val Arg 595 Asp Giu Gin Arg Arg Val Leu Ser Giy Asp Ala 590 Giu Ser Ser Asp Trp Val Val Val1 600 Asp Asp Ile Glu Al a 605 Phe Ser 610 Giy Val Gly Asp Leu Aia Gin Val Leu Giy His <210> 168 (211> 439 <212> PRT <213> Aspergiiius niger <400> 168 Met Arg Thr Ser Thr Leu Leu Leu Leu Ser Thr Aia Gly Ala Aia Leu Ala Ser Pro Tyr Pro Leu Pro Asp 25 Asp His Glu Val Pro Asn Thr Gin Gly Ser Gin Val Val Phe Ala Ala Asp Giu Ala Lys His Val 273/282 Ile Leu Ser Ala Leu Asn Ala His Ser Asp Pro Val 55 Ala Ala Met Val Ser Leu Arg Pro Glu Thr 70 Ala Ala Phe Leu Glu Pro Arg Leu Leu His Ile Arg Gly Glu Glu Lys Ala Glu -Trp 90 Met Thr Glu Gly Asp Lys Leu Arg Leu Gin Asp Phe 115 Arg 100 Gin Arg Gly Lys Lys 105 Phe Met Asp Ile Thr Glu His 110 Gly Asp Pro Tyr Ala Glu Gin Met Ala Ser Phe Asn Leu 130 Pro Lys Leu Ser Lys Gly Leu Val Pro Leu Phe Ser Gin 145 Ile Glu Thr Glu Arg 150 Met His Asp Ile Leu 155 Gin His Met Thr Tyr Tyr Asn Arg Tyr Gly Asp Tyr Gly Glu Met Ser Ser Glu 175 Trp Leu His Thr His Ile 195 Asp 180 Tyr Ile Ala Ala Ile Ser Lys Ser Pro Phe Arg 190 Gin Ser Ser Ser Leu Glu Tyr Phe 200 Thr His Pro Phe Arg 205 Ile Ile 210 Ala Arg Phe Glu Lys Val Arg Ser Phe Ser Gin Pro Leu 220 Tyr Leu Phe Pro Leu Thr 225 Ile Ile Gly Ala Gin Asp Ser Ala Leu Pro Ala Pro Gly 245 Ala Asp Asp Asp Ser Gly Thr Val Ser Ile 255 Leu Glu Ala Phe 260 Arg Val Leu Ala Asn Gly Tyr Thr Pro Lys Asp 270 Gly Pro Val 275 Glu Phe His Trp Tyr 280 Ala Ala Glu Glu Ala Gly Leu Leu 285 274/282 Gly Ser 290 Gin Ala Ile Ala Tyr Lys Lys Glu Gly Ala Lys Ile Asp 305 Ala Met Met Glu Phe 310 Asp Met Thr Ala Phe 315 Ile Ala Arg Asn Ala 320 Thr Glu Thr Ile Gly 325 Phe Val Ala Thr Ala Asp Ala Ala Leu Thr 335 Asn Trp Ala Val Tyr Glu 355 Asn Leu Ser Arg Tyr Ile Ser Ile Pro Ala Glu 350 Ser Tyr Thr Leu Gly Pro Asn Gly Ser Asp Tyr Lys Leu 370 Asn Tyr Pro Ala Phe Ala Ser Glu Gly Asn Pro Leu Ala 380 Val His Gly Ile Lys Gly Ser Phe Pro Gly 390 Glu Met Asp Pro Asp Arg Met Asp Val 405 Asp Asp Glu Thr Gly 410 Val Phe Ser Ile Glu His 415 Met Ala Arg Phe 420 Ser Glu Leu Ala Ala Phe Val Val Glu Gin Ala 430 Gly Trp Asp 435 Asn Thr Trp Arg <210> 169 <211> 526 <212> PRT <213> Aspergillus niger <400> 169 Met Arg Ser Phe Ser Val Val Ala Ala 1 5 Ala Ser Leu Ala Gin Ala Ala Arg Pro 25 Ser Arg Pro Ala Ser Ser Lys.Ser Ala 40 Ser Leu Ala Leu Ser Trp Arg Leu Val Pro Lys Pro Ile Glu Ala Tyr Ala Thr Thr Gly 275/282 Phe Giu Gin Leu Leu Asp His Asn Pro Giu Gi Th PeSe Gly Thr Phe Ser Gin Arg Tyr Trp Trp Thr Giu Tyr Trp Gly 75 Gly Pro Gly Ser Pro Glu Gly Val Val Leu Phe Asn Pro Gly Glu Val Ala Asp Gly Tyr Tyr Leu Thr Gly Ala Val 115 Asn 100 Asp Thr Leu Thr Val Tyr Ala Gin Giu Ile Gin 110 Ser Ser Pro Ile Leu Ile Glu His 120 Arg Tyr Trp Gly Tyr Giu 130 Val Leu Asn Ala Thr Leu Gin Tyr Leu Thr Leu Asp Gin 140 Vai Lys Leu Gin Phe Ser 145 Ile Leu Asp Met Tyr Phe Ala Giu Thr 155 Asp Asn Ser Ser Arg 165 Ser Asn Ala Gin Ala Pro Trp Vai Met Vai 1,75 Gly Gly Ser Pro Gly Thr 195 Tyr 180 Ser Giy Ala Leu Thr 185 Ala Trp Thr Giu Ser Ile Ala 190 Val Giu Ala Phe Trp Ala Tyr Ala Thr Ser Ala Ile Tyr 210 Asp Phe Trp Gin Phe Tyr Pro Ile Gin 220 Gin Gly Met Ala Gin 225 Asn Cys Ser Lys Val Ser Leu Val Ala 235 Giu Tyr Val Asp Ile Gly Lys Asn Gly 245 Thr Ala Lys Glu Gin Giu Leu Lys Glu Leu 255 Phe Gly Leu Pro Asn Gly 275 Gly 260 Ala Val Giu His Tyr 265 Asp Asp Phe Ala Aia Val Leu 270 Thr Gly Tyr Pro Tyr Leu Trp Asp Asn Asp Phe 276/282 Ser Ser 290 Phe Phe Gin Phe Asp Ala Val Giu Val Giu Ala Gly Al a 305 Ala Val Thr Pro Gl y 310 Pro Giu Gly Val Gly 315 Leu Glu Lys Ala Ala Asn Tyr Ala Trp Phe Asn Ser Thr 330 Ile Leu Pro Asri Tyr Cys 335 Ala Ser Tyr Ser Tyr Asn 355 Gl y 340 Tyr Trp Thr Asp Giu Trp Ser Val Ala 345 Phe Thr Asp Thr Ser 365 Cys Phe Asp 350 Val Gly Asn Ala Ser Ser Pro Ile 360 Pro Val 370 Asp Arg Gin Trp Trp Phe Leu Cys Glu Pro Phe Phe Trp 385 Leu Trp Gin Asp Gly Val Ser Ala Ser 405 Pro Glu Gly Thr Ser 395 Thr Ile Val Pro Tyr Trp Gin Arg Cys Pro Leu Tyr Phe Pro 415 Glu Val Asn Thr Val Asn 435 Tyr Thr Tyr Gly Ser 425 Ala Lys Gly Lys Asn Ser Ala 430 Asn Thr Thr Ser Trp Thr Gly Trp Asp Met Thr Arg Leu 450 Ile Trp Thr Asn Gin Tyr Asp Pro T rp 460 Arg Asp Ser Gly Ser Ser Thr Phe Arg 470 Pro Gly Gly Pro Val Ser Thr Ala Asn 480 Glu Pro Val Gin Ile Pro Gly Gly His Cys Ser Asp Leu Tyr 495 Met Glu Asp Giu Val Lys 515 Tyr 500 Tyr Ala Asn Glu Gi y 505 Val Arg Lys Val Val Asp Asn 510 Gin Ile Lys Glu Val Giu Glu Tyr Tyr Ala 525 277/282 <210> <211> <212> <213> 170 424 PRT Aspergillus niger <400> 170 Met 1 Gin Leu Leu Gin Ser Leu Ile Val Ala Val Cys Phe Ser Tyr Gly Val Leu Ser Phe Lys Val Leu Pro His Gly Pro Ser 25 Asn Gin His Lys Ala Arg Ser His Gly Pro Glu Arg Val Arg Gly Thr Gly Ala Leu Ala Ala Leu Arg Lys Ala Tyr Arg Lys Tyr Gly Ala Pro Ser Ser Phe Asn Ilie Asp Leu Asp Phe Lys Pro Thr Thr Thr His Ala Ala Gly Ser Ile Ala Giu Pro Gin Thr Gly Ala Val Ser Ala Thr Ser Gly Giy Gin 115 Val1 100 Giu Asn Asp Ala Giu 105 Phe Val Ser Pro Val Leu Ile 110 Ser Asp Phe Lys Ile Val Met Phe Asp Thr Gly Ser 125 Trp Vai 130 Phe Asp Thr Asn Leu 135 Asn Giu Thr Leu Thr 140 Gly His Thr Giu Tyr 145 Asn Pro Ser Asn Ser Thr Phe Lys Met Asp Gly Tyr Phe Asp Val Ser Gly Asp Asp Ser Ala Ser Gly Pro Val Gly 175 Thr Asp Thr Gly Val Pro 195 Val 180 Asn Ile Gly Gly Ala 185 Ile Val Lys Giu Gin Ala Phe 190 Thr Asn Ser Asp Gin Val Ser Gin 200 Ser Phe Ilie Giu Asp 205 278 /282 Asn Gly 210 Leu Val Gly Leu Gly 215 Phe Ser Ser Ile Asn 220 Thr Ile Lys Pro Ala Gin Asp Thr Phe 230 Phe Ala Asn Val Al a 235 Pro Ser Leu Asp Giu 240 Pro Val Met Thr Al a 245 Ser Leu Lys Ala Gly Vai Gly Giu Tyr Giu 255 Phe Giy Thr Ser Val Asp 275 Asp Lys Asp Lys Tyr 265 Gin Gly Asn Ile Ala Asn Ile 270 Pro Lys Tyr Ser Ser Asn Gly Trp Gin Phe Ser Th r 285 Ser Val 290 Ala Asp Gly Giu Leu 295 Lys Asp Ile Gly Leu Asn Thr Ser Ile 305 Ala Asp Thr Gly Ser Leu Met Leu Leu 315 Asp Glu Asp Vai Val1 320 Thr Ala Tyr Tyr Gin Val Pro Asn Val Tyr Val Ser Ser Ala 335 Giy Gly Tyr Vai Leu Gly 355 Tyr Pro Cys Asn Thr 345 Thr Leu Pro Ser Phe Ser Leu 350 Leu Ile Asn Giu Ser Ser Leu Thr Ile Pro Gly Phe Ser 370 Lys Val Gly Thr Asn 375 Thr Thr Thr Gly Gin 380 Ala Leu Cys Phe Gi y 385 Gly Ile Gin Ser Giy Asn Thr Ser Leu 395 Gin Ile Leu Gly Asp 400 Ile Phe Leu Lys Phe Phe Val Val Asp Met Arg Gly Pro Ser 415 Leu Gly Vai Ser Pro Lys Asn <210> '211> <212> 171 548 PRT <213> Aspergilius nicer 279 /282 <400> 171 Met 1 Arg Ile Asp Ala Ala Leu His Le u 10 Val Pro Val Leu Leu Gly Gin Val Gly Al a Leu Gin Leu Pro Val Gin Asp Ser Asn Ser Gin Trp Gin Lys Pro Asn Ala Gly Asp Lys Pro Leu Ile Ser Ser Pro Leu Leu Gin Glu Gin Val Lys Giu Asn Leu Leu Arg Ala Arg Gin Tyr Lys Ile Ala Glu Leu Gly Glu Asp Glu Tyr Asn His Pro Arg Val Ile Giy Lys Gly His Leu Thr Leu Asp Tyr Ile Tyr Ser Thr Leu Phe Pro Ala 115 Th r 100 Asp Leu Gly Asp T yr 105 Tyr Thr Val Val Asn Gin Ser 110 Vai Leu Gly Val Ser Gly Asn Phe Giu Ser Arg His Asp 130 Val Pro Lys Ser Thr Pro Met Gly Leu 140 Thr Pro Pro Thr Arg 145 Asn Lys Glu Pro Val 150 Tyr Gly Ser Leu Ala Val Ser Asn Leu 160 Gly Cys Glu Ala Ser 165 Asp Tyr Ser Ser Asn 170 Leu Lys Gly Ala Val Ala 175 Phe Ile Ser Gly Lys Ala 195 Gly Ser Cys Pro Gly Thr Lys Ser Gin Leu Ala 190 Glu Arg Gly Gly Ala Val Ala Val Ile Tyr Asn As n 205 Asp Leu 210 Ser Gly Thr Leu Giy 215 Asn Pro Thr Pro Asp 220 His Val Ala Thr Phe Gly Ile Ser Asp Glu Asp Ala Ala Pro Val Leu Giu Lys Leu Asn 280/I282 240 Lys Gly Glu Lys Asp Ala Ile Ala Val Asp Ala Ile Val Glu 255 Thr Ile His Thr Thr Asn Ile Ile 260 Val Met Leu Gly Gly Gin Thr Thr Asp Gly Asp Pro 270 Ala Glu Gly Asn Asn Cys 275 His Ser Asp Ser Val1 285 Pro Gly 290 Ile Asn Asp Asp Gly 295 Ser Gly Thr Leu Leu Leu Glu Leu Al a 305 Thr Leu Leu Thr Phe Arg Val Asn As n 315 Cys Val Arg Phe Al a 320 Trp Trp Ala Ala Glu Glu Gly Leu Gly Ser Asp Tyr Tyr Val 335 Ser Val Leu Tyr Asp Met 355 Thr 340 Pro Glu Glu Asn Arg 345 Lys Ile Arg Leu Phe Met Asp 350 Tyr Asn Ala Leu Gly Ser Pro Phe Ala Tyr Gin Thr Asn 370 Ala Val Asn Pro Glu 375 Gly Ser Glu Glu Arg Asp Leu Tyr Thr 385 Asp Phe Tyr Glu His Gly Phe Asn Thr Tyr Ile Pro Asp Gly Arg Ser Tyr Asp Ala Phe Arg His Gly Ile Pro Gly 415 Gly Gly Ile Asp Met Phe 435 Thr Gly Ala Glu Gi y 425 Ile Lys Thr Val Glu Glu Ala 430 Cys Tyr His Gly Gly Val Ala Gin Trp Tyr Asp Gin Ile 450 Cys Asp Thr Val Al a 455 Asn Val Asn Leu Thr 460 Ala Trp Glu Trp Asn Thr Lys Leu Val Ala His Ser Ile Ala Thr Tyr Ala Lys Ser Phe 281 /282 465 Asp Gly Giu Glu Thr Thr Thr Ala 530 480 00 Phe Pro Giu Arq Ser Asp Giu Pro Ile Ser Pro Ala Ala Phe 485 490 495 Pro Lys Tyr His Gly His Ala Leu Gin Leu Leu Arg Gly Asn 500 505 510 Gly Thr Gin Ser Val Leu Trp Gly Ala Gin Ile Gin Asn Gly 515 520 525 Ala Ser Val Leu Asn Leu Leu Ser Ile Arg Arg Arg Gly Thr 535 540 Phe 545 Ser Leu Ser 282 /282