WO2001000845A1 - Genes de corynebacterium glutamicum pour la biosynthese de l'acide folique et leur utilisation pour la production microbienne d'acide folique - Google Patents

Genes de corynebacterium glutamicum pour la biosynthese de l'acide folique et leur utilisation pour la production microbienne d'acide folique Download PDF

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Publication number
WO2001000845A1
WO2001000845A1 PCT/EP2000/005864 EP0005864W WO0100845A1 WO 2001000845 A1 WO2001000845 A1 WO 2001000845A1 EP 0005864 W EP0005864 W EP 0005864W WO 0100845 A1 WO0100845 A1 WO 0100845A1
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WIPO (PCT)
Prior art keywords
polypeptide
folic acid
seq
amino acids
deletion
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PCT/EP2000/005864
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German (de)
English (en)
Inventor
Matthias Mack
Karin Herbster
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Basf-Lynx Bioscience Ag
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Publication date
Application filed by Basf-Lynx Bioscience Ag filed Critical Basf-Lynx Bioscience Ag
Priority to AU59782/00A priority Critical patent/AU5978200A/en
Priority to CA002377458A priority patent/CA2377458A1/fr
Priority to EP00945815A priority patent/EP1194565A1/fr
Priority to KR1020017016565A priority patent/KR20020026469A/ko
Publication of WO2001000845A1 publication Critical patent/WO2001000845A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • C07K14/34—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Corynebacterium (G)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10—Transferases (2.)
    • C12N9/1085—Transferases (2.) transferring alkyl or aryl groups other than methyl groups (2.5)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/52—Genes encoding for enzymes or proenzymes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10—Transferases (2.)
    • C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
    • C12N9/1235—Diphosphotransferases (2.7.6)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/78—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/88—Lyases (4.)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/18—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
    • C12P17/182—Heterocyclic compounds containing nitrogen atoms as the only ring heteroatoms in the condensed system

Definitions

  • the present invention relates to the production process for folic acid by fermentation using a genetically modified organism.
  • This invention consists of the nucleotide sequences of four genes (folE, folP, folB and folK) from Corynebacterium glutamicum for folic acid biosynthesis and their use for the microbial production of folic acid. These four genes form an operon and are transcribed in the following order: folE, folP, folB, folK.
  • Folic acid is essential for animal organisms. Its derivative tetrahydrofolate is a very versatile carrier of activated single-carbon units in cells of the animal organism. Folic acid consists of three groups: a substituted pteridine ring, p-aminobenzoate and glutamate. Mammals cannot synthesize a pteridine ring. They take in folic acid from food and from microorganisms in their intestinal tract. Folic acid deficiency mainly leads to lesions in the mucous membranes.
  • Folic acid is mainly used as a food additive.
  • Microorganisms can be used for the fermentative production of folic acid. They can be optimized in their folic acid biosynthesis performance by genetically modifying the biosynthetic pathway of folic acid.
  • genetic engineering means increasing the number of copies and / or the rate of transcription of the genes of the biosynthetic pathway for folic acid.
  • the proportion of gene product and thus also the intracellular enzyme activity increases.
  • Increased enzyme activity leads to an increased rate of conversion of food (eg glucose) to folic acid and thus to an increased product concentration.
  • the nucleotide sequences of the genes of the folic acid biosynthetic pathway must be identified.
  • This invention is concerned with four new gene sequences for the folic acid biosynthesis from Corynebacterium glutamicum and with their use for the microbial production of folic acid.
  • Part of the invention is the folE gene product.
  • SEQ ID NO. 2 describes a polypeptide sequence.
  • the folE gene product encodes a polypeptide of 202 amino acids with a molecular weight of 22029 Da.
  • the present invention is also concerned with functional derivatives of this polypeptide, which can be obtained if one in SEQ ID NO. 2 one or more amino acids, preferably up to 25% of the amino acids, preferably up to 15% of the amino acids, are replaced by deletion, insertion or substitution or by a combination of deletion, insertion and substitution.
  • the term functional derivative means that the enzymatic activity of the derivative is still in the same order of magnitude as that of the polypeptide with the sequence SEQ ID NO. 2.
  • Another part of the invention is the folP gene product.
  • SEQ ID NO. 4 describes a polypeptide sequence.
  • the folP gene product encodes a polypeptide of 285 amino acids with a molecular weight of 29520 Da.
  • the present invention is also concerned with functional derivatives of this polypeptide, which can be obtained if one in SEQ ID NO. 4 one or more amino acids, preferably up to 40% of the amino acids, preferably up to 25% of the amino acids, are replaced by deletion, insertion or substitution or by a combination of deletion, insertion and substitution.
  • the term functional derivative means that the enzymatic activity of the derivative is still of the same order of magnitude as that of the polypeptide with the sequence SEQ ID NO. 4th
  • SEQ ID NO. 6 describes a polypeptide sequence.
  • the folB gene product encodes a polypeptide of 131 amino acids with a molecular weight of 14020 Da.
  • the present invention is also concerned with functional derivatives of this polypeptide, which can be obtained if one in SEQ ID NO. 6 one or more amino acids, preferably up to 30% of the amino acids, preferably up to 20% of the amino acids, are replaced by deletion, insertion or substitution or by a combination of deletion, insertion and substitution.
  • the term functional derivative means that the enzymatic activity of the derivative is still of the same order of magnitude as that of the polypeptide with the sequence SEQ ID R. 6.
  • SEQ ID NO. 8 describes a polypeptide sequence.
  • the folK gene product encodes a polypeptide of 160 amino acids with a molecular weight of 18043 Da.
  • the present invention is also concerned with functional derivatives of this polypeptide, which can be obtained if one in SEQ ID NO. 8 by deletion, insertion or substitution or by a combination of deletion, Insertion and substitution of one or more amino acids, preferably replacing up to 40% of the amino acids, preferably up to 30% of the amino acids.
  • functional derivative it is meant that the enzymatic activity of the derivative is still in the same order of magnitude as that of the polypeptide with the sequence SEQ ID NO. 8th.
  • polynucleotide sequences which encode the polypeptides described above.
  • the polynucleotide sequences can be generated starting from sequences which are isolated from Corynebacterium glutamicum (ie SEQ ID NO. 1, 3, 5 and 7) by modifying these sequences by site-directed mutagenesis or after back-translating the corresponding polypeptide with genetic code carries out a total chemical synthesis.
  • polynucleotide sequences can preferably be used for the transformation of host organisms, and preferably of microorganisms, in the form of gene constructs which contain at least one copy of one of these polynucleotides together with at least one regulatory sequence.
  • Regulatory sequences include promoters, terminators, enhancers and ribosomal binding sites.
  • Preferred host organisms for the transformation with these gene constructs are Coryneibacterium and Bacillus species. Any eukaryotic microorganism can also be used, preferably yeast strains of the genus Ashbya, Candlda, Plchla, Saccharomyces and Hansenula.
  • Another part of the invention consists in the process for the preparation of folic acid by culturing a host organism which is transformed in the manner described above and in the subsequent isolation of the folic acid.
  • the trained personnel are familiar with the processes and procedures for cultivating microorganisms and isolating folic acid from a microbial production.
  • DNA from the genome of Corynebacterium glutamlcum ATCC 13032 can be obtained by standard methods which have already been described, e.g. B. by J. Altenbuchner and J. Cullum (1984, Mol. Gen. Genet. 195: 134-138).
  • the genome library can be prepared according to standard regulations (e.g. Sambrook, J. et al. (1989) Molecular cloning: a laboratory manual, Cold Spring Harbor Laboratory Press) with any cloning vector, e.g. pBluescript II KS- (Stratagene) or ZAP Express TM (Stratagene). Any fragment size can be used, preferably 5'au3AI fragments with a length of 2-9 kb, which can be integrated into cloning vectors with digested BamHI.
  • E. coli clones can be selected from the genome library shown in Example 1.
  • E. coli cells are cultivated according to standard ancestors in suitable media (e.g. LB supplemented with 100 mg / 1 ampicillin), after which the plasmid DNA can be isolated. If one clones genome fragments from the DNA of Corynebacterium glutamlcum in pBluescript II KS- (see Example 1), the DNA can be sequenced with the help of the oligonucleotides 5 '-AATTAACCCTCACTAAAGGG-3' and 5'-GTAATACGACTCACTATAGGGC-3 '.
  • nucleotide sequences can e.g. using the BLASTX algorithm (Altschul et al. (1990) J. Mol. Biol. 215: 403-410). In this way, one can discover new sequences and elucidate the function of these new genes.
  • Example 3 The analysis of the E. coli clones, as described in Example 2, which was followed by the analysis of the sequences obtained in Example 3, resulted in a sequence as described with SEQ ID NO. 3 is described.
  • this sequence showed similarity to dihydropteroate synthases (FolP; EC 2.5.1.15) from different organisms. The greatest similarity was with the dihydropteroate synthase (FolP) from Mycobacterlum tuberculosls (NRDB 006274; 53% agreement at the amino acid level).
  • Example 3 When the E. coli clones were analyzed as described in Example 2, followed by the analysis of the sequences obtained in Example 3, a sequence was obtained as described with SEQ ID NO. 5 is described.
  • this sequence showed similarity to dihydroneopterin aldolases (FolB; EC 4.1.2.25) from different organisms. The greatest similarity 5 was with the dihydroneopterin aldolase (FolB) from Mycobacterlum tuberculosis (NRDB 006275; 61% agreement at the amino acid level).
  • Example 5 The analysis of the E. coli clones as described in Example 2, which was followed by the analysis of the sequences obtained in Example 3, resulted in one Sequence as shown with SEQ ID NO. 7 is described.
  • this sequence showed similarity with 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinases (FolK; EC 2.7.6.3) from different organisms. The greatest similarity was with that
  • GTP cyclohydrolase I for dihydropteroate synthase, for dihydroneopterin aldolase and for 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase from Corynebacterium glutamicum for the production of folic acid
  • the genes for the GTP cyclohydrolase I, for the dihydropteroate synthase, for the dihydroneopterin aldolase and for the 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase from Corynebacterium glutamicum can be obtained with the aid of suitable cloning and expression systems introduce into Corynebacterium glutamicum or into any other microorganism. Genetically modified microorganisms can be produced which differ from the wild-type organism with regard to the activity or the number of gene copies. These new, genetically modified strains can be used to produce folic acid.
  • SEQ ID NO. 1 DNA (folE)
  • SEQ ID NO. 2 amino acid (FolE)
  • SEQ ID NO. 3 DNA (folP)
  • SEQ ID NO. 4 amino acid (FolP)
  • SEQ ID NO. 6 amino acid (FolB)
  • SEQ ID NO. 7 DNA (folK)
  • SEQ ID NO. 8 amino acid (FolK)

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Biomedical Technology (AREA)
  • Microbiology (AREA)
  • Medicinal Chemistry (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

L'invention concerne des séquences nucléotidiques de quatre gènes (folE, folP, folB et folK) de Corynebacterium glutamicum servant à la biosynthèse de l'acide folique et leur utilisation pour la production microbienne d'acide folique.
PCT/EP2000/005864 1999-06-25 2000-06-23 Genes de corynebacterium glutamicum pour la biosynthese de l'acide folique et leur utilisation pour la production microbienne d'acide folique WO2001000845A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
AU59782/00A AU5978200A (en) 1999-06-25 2000-06-23 Genes from corynebacterium glutamicum for the biosynthesis of folic acid and their use for the microbial production of folic acid
CA002377458A CA2377458A1 (fr) 1999-06-25 2000-06-23 Genes de corynebacterium glutamicum pour la biosynthese de l'acide folique et leur utilisation pour la production microbienne d'acide folique
EP00945815A EP1194565A1 (fr) 1999-06-25 2000-06-23 Genes de corynebacterium glutamicum pour la biosynthese de l'acide folique et leur utilisation pour la production microbienne d'acide folique
KR1020017016565A KR20020026469A (ko) 1999-06-25 2000-06-23 엽산 생합성을 위한 코리네박테리움 글루타미쿰으로부터의유전자, 및 미생물에 의한 엽산 생산에 있어서 그들의 용도

Applications Claiming Priority (2)

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DE19929363.5 1999-06-25
DE19929363A DE19929363A1 (de) 1999-06-25 1999-06-25 Gene aus Corynebacterium glutamicum für die Folsäurebiosynthese und ihr Einsatz zur mikrobiellen Herstellung von Folsäure

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EP (1) EP1194565A1 (fr)
KR (1) KR20020026469A (fr)
CN (1) CN1371418A (fr)
AU (1) AU5978200A (fr)
CA (1) CA2377458A1 (fr)
DE (1) DE19929363A1 (fr)
WO (1) WO2001000845A1 (fr)
ZA (1) ZA200200582B (fr)

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1262541A1 (fr) * 2001-05-28 2002-12-04 Stichting Top-Instituut Voedselwetenschappen Production de l'acide folique biodisponible
US6680187B2 (en) 2000-09-13 2004-01-20 Degussa Ag Nucleotide sequences coding for the PTSI protein
US6689587B2 (en) 2000-11-10 2004-02-10 Degussa Ag Polynucleotides encoding the nadC gene and methods of producing nicotinic acid or nicotinic acid derivatives
US6692946B2 (en) 2000-11-10 2004-02-17 Degussa Ag Polynucleotides encoding the nadA gene and methods of producing nicotinic acid or nicotinic acid derivatives
US6759224B2 (en) 2000-09-09 2004-07-06 Degussa Ag Nucleotide sequences which code for the sahH gene
US6812016B2 (en) 2000-09-02 2004-11-02 Degussa Ag Nucleotide sequences which code for the metY gene
US6812006B2 (en) 2000-08-10 2004-11-02 Degussa Ag Nucleotide sequences which code for the lysR3 gene
US6815196B2 (en) 2000-09-02 2004-11-09 Degussa Ag Nucleotide sequences encoding o-succinylhomoserine sulfhydrylase
US6875586B2 (en) 2000-08-10 2005-04-05 Degussa Ag Nucleotide sequences coding for the luxR gene
US6893852B1 (en) 1999-07-02 2005-05-17 Ajinomoto Co., Inc. Dna encoding sucrose pts enzyme II
US6902916B2 (en) 2000-08-10 2005-06-07 Degussa Ag Nucleotide sequences coding for the 1ysR1 gene
US6942996B2 (en) 2000-08-02 2005-09-13 Degussa Ag Isolated polynucleotide from Corynebacterium encoding a homocysteine methyltransferase
US6958228B2 (en) 2000-08-02 2005-10-25 Degussa Ag Nucleotide sequence which code for the metH gene
US7038034B2 (en) 2000-09-09 2006-05-02 Degussa Ag Nucleotide sequences coding for the Dep33 efflux protein
US7105321B2 (en) 2000-08-26 2006-09-12 Degussa Ag Nucleotide sequences which code for the ccpA2 gene
US7468262B2 (en) 2003-05-16 2008-12-23 Ajinomoto Co., Inc. Polynucleotides encoding useful polypeptides in corynebacterium glutamicum ssp. lactofermentum

Families Citing this family (4)

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CN1952114B (zh) * 2005-10-20 2010-04-14 浙江爱迪亚营养科技开发有限公司 一种谷氨酸棒杆菌及其应用于制备烟酰胺的方法
CN109810991B (zh) * 2019-03-02 2021-11-12 昆明理工大学 二氢蝶酸合酶基因folP的用途
CN111235169A (zh) * 2020-02-03 2020-06-05 昆明理工大学 一种GTP环化水解酶I基因folE及应用
CN112852844A (zh) * 2021-03-05 2021-05-28 昆明理工大学 羟甲基二氢蝶呤焦磷酸激酶基因folK的用途

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EP0761818A1 (fr) * 1995-08-28 1997-03-12 Toray Industries, Inc. Procédé pour la préparation de l'acide folique

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EP0761818A1 (fr) * 1995-08-28 1997-03-12 Toray Industries, Inc. Procédé pour la préparation de l'acide folique

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IWAI K ET AL: "OCCURRENCE OF CRITHIDIA FACTORS AND FOLIC-ACID IN VARIOUS BACTERIA", JOURNAL OF BACTERIOLOGY, vol. 104, no. 1, 1970, pages 197 - 201, XP000960985, ISSN: 0021-9193 *

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6893852B1 (en) 1999-07-02 2005-05-17 Ajinomoto Co., Inc. Dna encoding sucrose pts enzyme II
US6958228B2 (en) 2000-08-02 2005-10-25 Degussa Ag Nucleotide sequence which code for the metH gene
US6942996B2 (en) 2000-08-02 2005-09-13 Degussa Ag Isolated polynucleotide from Corynebacterium encoding a homocysteine methyltransferase
US6812006B2 (en) 2000-08-10 2004-11-02 Degussa Ag Nucleotide sequences which code for the lysR3 gene
US7173105B2 (en) 2000-08-10 2007-02-06 Degussa Ag Nucleotide sequences coding for the LuxR gene
US6902916B2 (en) 2000-08-10 2005-06-07 Degussa Ag Nucleotide sequences coding for the 1ysR1 gene
US6875586B2 (en) 2000-08-10 2005-04-05 Degussa Ag Nucleotide sequences coding for the luxR gene
US7105321B2 (en) 2000-08-26 2006-09-12 Degussa Ag Nucleotide sequences which code for the ccpA2 gene
US6812016B2 (en) 2000-09-02 2004-11-02 Degussa Ag Nucleotide sequences which code for the metY gene
US6815196B2 (en) 2000-09-02 2004-11-09 Degussa Ag Nucleotide sequences encoding o-succinylhomoserine sulfhydrylase
US7038034B2 (en) 2000-09-09 2006-05-02 Degussa Ag Nucleotide sequences coding for the Dep33 efflux protein
US6759224B2 (en) 2000-09-09 2004-07-06 Degussa Ag Nucleotide sequences which code for the sahH gene
US6680187B2 (en) 2000-09-13 2004-01-20 Degussa Ag Nucleotide sequences coding for the PTSI protein
US7160703B2 (en) 2000-09-14 2007-01-09 Degussa Ag Nucleotide sequences coding for the PtsI protein
US6692946B2 (en) 2000-11-10 2004-02-17 Degussa Ag Polynucleotides encoding the nadA gene and methods of producing nicotinic acid or nicotinic acid derivatives
US6689587B2 (en) 2000-11-10 2004-02-10 Degussa Ag Polynucleotides encoding the nadC gene and methods of producing nicotinic acid or nicotinic acid derivatives
EP1262541A1 (fr) * 2001-05-28 2002-12-04 Stichting Top-Instituut Voedselwetenschappen Production de l'acide folique biodisponible
WO2002097063A1 (fr) * 2001-05-28 2002-12-05 Campina B.V. Production d'acide folique biodisponible
US7468262B2 (en) 2003-05-16 2008-12-23 Ajinomoto Co., Inc. Polynucleotides encoding useful polypeptides in corynebacterium glutamicum ssp. lactofermentum
US7696315B2 (en) 2003-05-16 2010-04-13 Ajinomoto Co., Inc. Polynucleotides encoding useful polypeptides in Corynebacterium glutamicum ssp. lactofermentum
US7695946B2 (en) 2003-05-16 2010-04-13 Ajinomoto Co., Inc. Polynucleotides encoding useful polypeptides in Corynebacterium glutamicum ssp. lactofermentum

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CN1371418A (zh) 2002-09-25
DE19929363A1 (de) 2000-12-28
CA2377458A1 (fr) 2001-01-04
ZA200200582B (en) 2003-03-26
AU5978200A (en) 2001-01-31
EP1194565A1 (fr) 2002-04-10
KR20020026469A (ko) 2002-04-10

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