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EP1322766A2 - Procede pour modifier le genome de corynebacteries - Google Patents

Procede pour modifier le genome de corynebacteries

Info

Publication number
EP1322766A2
EP1322766A2 EP01982319A EP01982319A EP1322766A2 EP 1322766 A2 EP1322766 A2 EP 1322766A2 EP 01982319 A EP01982319 A EP 01982319A EP 01982319 A EP01982319 A EP 01982319A EP 1322766 A2 EP1322766 A2 EP 1322766A2
Authority
EP
European Patent Office
Prior art keywords
corynebacteria
corynebacterium
methylation pattern
acid
vector
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP01982319A
Other languages
German (de)
English (en)
Inventor
Markus Pompejus
Hartwig Schröder
Burkhard Kröger
Oskar Zelder
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Paik Kwang Industrial Co Ltd
Original Assignee
BASF SE
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by BASF SE filed Critical BASF SE
Priority to EP08075086A priority Critical patent/EP1921151A1/fr
Publication of EP1322766A2 publication Critical patent/EP1322766A2/fr
Withdrawn legal-status Critical Current

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Classifications

    • 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.)
    • C12N9/1003—Transferases (2.) transferring one-carbon groups (2.1)
    • C12N9/1007—Methyltransferases (general) (2.1.1.)
    • 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
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/74—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
    • C12N15/77—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora for Corynebacterium; for Brevibacterium

Definitions

  • the invention relates to a new method for changing the genome of Corynebacteria, use of these bacteria and new vectors.
  • the invention relates to a method for modifying corynebacteria with the aid of vectors which cannot be replicated in corynebacteria 10.
  • Corynebacterium glutamicu is a gram-positive, aerobic bacterium that (like other Corynebacteria, i.e. Corynebacterium and Brevibacteriu species) is used in the industry
  • DNA sequence sections can also be removed from the genome (e.g. genes or parts of genes), but sequence exchanges (e.g. base exchanges) can also be carried out in the genome.
  • the change in the genome can be achieved by introducing DNA into the cell, which preferably does not replicate in the cell, and by recombining this introduced DNA with genomic host DNA and thus changing the genomic DNA.
  • the methods known for this are complex and all have special problems (see, for example, van der Rest, ME et al. (1999) Appl. Microbiol. Biotechnol. 52, 541-545).
  • a known method is based on conjugation (Schwarzer & Pühler (1991) Biotechnology 9, 84-87).
  • the disadvantage is that special mobilizable plasmids have to be used which have to be conjugatively transferred from a donor strain (usually E. coli) to the recipient (for example Corynebacterium species). This method is also very labor intensive.
  • the heat shock response in bacteria in response to the heat shock has a variety of consequences for the metabolism of the cells (see e.g. Gross, CA. (1996), pp. 1382-1399 in Escherichia coli and Salmonella (Neidhart et al., Eds.) ASM press, Washington).
  • Corynebacteria in the sense of the invention are understood to be Corynebacterium species, Brevibacterium species and Mycobacterium species. Corynebacterium species and Brevibacterium species are preferred. Examples of Corynebacterium species and Brevibacterium species are: Brevibacterium brevis, Brevibacterium lactofermentum, Corynebacterium ammoniagenes, Corynebacterium glutamicum, Corynebacterium diphtheriae, Corynebacterium lactofermentum. Examples of Mycobacterium species are: Mycobacterium tuberculosis, Mycobacterium leprae, Mycobacterium bovis.
  • NRRL ARS Culture Collection, Northern Regional Research Laboratory, Peoria, EL, USA
  • NCIMB National Collection of Industrial and Marine Bacteria Ltd., Aberdeen, UK
  • DSMZ German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany
  • the invention discloses a new and simple method for changing genomic sequences in Corynebacteria. These can be genomic integrations of nucleic acid molecules (e.g. complete genes), disruptions (e.g. deletions or integrative disruptions) and sequence changes (e.g. single or multiple point mutations, complete gene exchanges).
  • nucleic acid molecules e.g. complete genes
  • disruptions e.g. deletions or integrative disruptions
  • sequence changes e.g. single or multiple point mutations, complete gene exchanges.
  • methyltransferases in particular the cglIM gene, can also be used to integrate DNA into the genome of Corynebacterium glutamicum, for example to disrupt or overexpress genes in the genome. This is also possible with other methyltransferases introducing the Corynebacteria-specific methylation pattern.
  • a vector which cannot be replicated in the corynebacterium to be transformed is used for this.
  • a non-replicable vector means a DNA that cannot replicate freely in Corynebacteria. It is possible that this DNA can replicate freely in other bacteria if, for example, it carries an appropriate origin of replication. However, it is also possible that this DNA cannot replicate in other bacteria if, for example, a linear DNA is used.
  • the method according to the invention is based on a direct transformation of C. glutamicum (e.g. by electroporation) without having to use special methods of culturing the cells to be transformed or special methods during the transformation (such as heat shock etc.).
  • the transformation can also be carried out with the addition of restriction endonucleases (as described in DE19823834).
  • the advantage of the method according to the invention is that the introduced DNA is not recognized as foreign DNA and therefore is not broken down by the restriction system.
  • Another advantage of the method according to the invention is that no conjugation has to be carried out - this considerably reduces the amount of work and allows improved flexibility in the choice of the plasmids used.
  • Another advantage is that no special strains of Corynebacteria have to be used and that no special treatment of the strains to be transformed is necessary, in particular no heat shock is necessary. See example for experimental details.
  • Fine chemicals are understood to mean: organic acids, both proteinogenic and non-proteinogenic amino acids, nucleotides and nucleosides, lipids and fatty acids, diols, carbohydrates, aromatic compounds, vitamins and cofactors as well as enzymes.
  • fine chemical is known in the art and includes molecules that are produced by an organism and have applications in various industries, such as, but not limited to, the pharmaceutical, agricultural, and cosmetic industries. These compounds include organic acids such as tartaric acid, itaconic acid and diamino-pimelic acid, both proteinogenic and non-proteinogenic amino acids, purine and pyrimidine bases, nucleosides and nucleotides (as described, for example, in Kuninaka, A. (1996) Nucleotides and related compounds, pp. 561-612, in Biotechnology Vol. 6, Rehm et al., ed. VCH: Weinheim and the citations contained therein), lipids, saturated and unsaturated fatty acids (e.g.
  • arachidonic acid arachidonic acid
  • diols e.g. propanediol and butanediol
  • carbohydrates e.g. hyaluronic acid and trehalose
  • aromatic compounds e.g. aromatic amines, vanillin and indigo
  • vitamins and cofactors as described in Ullmann's Encyclopedia of Industrial Chemistry, Vol. A27, "Vitamins", Pp. 443-613 (1996) VCH: Weinheim and the citations contained therein; and Ong, AS, Niki, E. and Packer, L.
  • amino acids comprise the basic structural units of all proteins and are therefore essential for normal cell functions.
  • amino acid is known in the art.
  • the proteinogenic amino acids of which there are 20 types, serve as structural units for proteins in which they are linked to one another via peptide bonds, whereas the non-proteinogenic amino acids (of which hundreds are known) are usually not found in proteins (see Ullmann's Encyclopedia of Industrial Chemistry, Vol. A2, pp. 57-97 VCH: Weinheim (1985)).
  • the amino acids can be in the D- or
  • L-amino acids are usually the only type found in naturally occurring proteins finds. Biosynthetic and degradation pathways of each of the 20 proteinogenic amino acids are well characterized in both prokaryotic and eukaryotic cells (see, for example, Stryer, L. Biochemistry, 3rd edition, pp. 578-590 (1988)).
  • the "essential" amino acids histidine, isoleucine, leucine, lysine, methionine,
  • Phenylalanine, threonine, tryptophan and valine are converted into the remaining 11 "non-essential" amino acids (alanine, arginine, asparagine, aspartate, cysteine, glutamate) by simple biosynthetic routes , Glutamine, glycine, proline, serine and tyrosine). Higher animals have the ability to synthesize some of these amino acids, but the essential amino acids must be ingested with food for normal protein synthesis to take place.
  • Lysine is not only an important amino acid for human nutrition, but also for monogastric animals such as poultry and pigs.
  • Glutamate is most commonly used as a flavor additive (monosodium glutamate, MSG) and is widely used in the food industry, as well as aspartate, phenylalanine, glycine and cysteine.
  • Glycine, L-methionine and tryptophan are all used in the pharmaceutical industry.
  • Glutamine, valine, leucine, isoleucine, histidine, arginine, proline, serine and alanine are used in the pharmaceutical and cosmetic industries. Threonine, tryptophan and D- / L-methionine are widespread feed additives (Leuchtenberger, W. (1996) Amino aeids - technical produetion and use, pp. 466-502 in Rehm et al., (Ed.) Biotechnology Vol. 6, chapter 14a, VCH: Weinheim).
  • amino acids can also be used as precursors for the synthesis of synthetic amino acids and proteins such as N-acetylcysteine, S-carboxymethyl-L-cysteine, (S) -5-hydroxytryptophan and others, in Ullmann's Encyclopedia of Industrial Chemistry, Vol. A2, pp. 57-97, VCH, Weinheim, 1985 are suitable substances.
  • Cysteine and glycine are each produced from serine, the former by condensation of homocysteine with serine, and the latter by transferring the side chain ⁇ -carbon atom to tetrahydrofolate, in a reaction catalyzed by serine transhydroxymethylase.
  • Phenylalanine and tyrosine are synthesized from the precursors of the glycolysis and pentose phosphate pathways, erythrose-4-phosphate and phosphoenolpyruvate in a 9-step biosynthetic pathway that only differs in the last two steps after the synthesis of prephenate. Tryptophan is also produced from these two starting molecules, but its synthesis takes place in an 11-step process.
  • Tyrosine can also be prepared from phenylalanine in a reaction catalyzed by phenylalanine hydroxylase.
  • Alanine, valine and leucine are each biosynthetic products from pyruvate, the end product of glycolysis.
  • Aspartate is made from oxaloacetate, an intermediate of the citrate cycle.
  • Asparagine, methionine, threonine and lysine are each produced by converting aspartate.
  • Isoleucine is made from threonine.
  • histidine is formed from 5-phosphoribosyl-1-pyrophosphate, an activated sugar.
  • Amino acids the amount of which exceeds the cell's protein biosynthesis requirements, cannot be stored and are instead broken down, so that intermediate products are provided for the main metabolic pathways of the cell (for an overview see Stryer, L., Biochemistry, 3. Ed. Chapter 21 "Amino Acid Degradation and the Urea Cycle”; S 495-516 (1988)).
  • the cell is able to convert unwanted amino acids into useful metabolic intermediates, the production of amino acids is expensive in terms of energy, precursor molecules and the enzymes required for their synthesis.
  • Vitamins, cofactors and nutraceuticals comprise another group of molecules. Higher animals have lost the ability to synthesize them and must therefore absorb them, although they are easily synthesized by other organisms such as bacteria. These molecules are either biologically active molecules per se or precursors of biologically active substances that serve as electron carriers or intermediates in a number of metabolic pathways. In addition to their nutritional value, these compounds also have a significant industrial value as dyes, antioxidants and catalysts or other processing aids. (For an overview of the structure, activity and industrial applications of these compounds, see, for example, Ullmann's Encyclopedia of Industrial Chemistry, "Vitamins", Vol. A27, pp. 443-613, VCH: Weinheim, 1996).
  • vitamin is known in the art and encompasses nutrients which are required by an organism for normal function, but which cannot be synthesized by this organism itself.
  • the group of vitamins can include cofactors and nutraceutical compounds.
  • cofactor includes non-proteinaceous compounds that are necessary for normal enzyme activity to occur. These compounds can be organic or inorganic; the cofactor molecules according to the invention are preferably organic.
  • nutraceutical encompasses food additives which are beneficial to plants and animals, in particular humans. Examples of such molecules are vitamins, antioxidants and also certain lipids (e.g. polyunsaturated fatty acids).
  • Thiamine (vitamin B x ) is formed by chemical coupling of pyrimidine and thiazole units.
  • Riboflavin (vitamin B 2 ) is synthesized from guanosine 5'-triphosphate (GTP) and ribose 5'-phosphate. Riboflavin in turn is used to synthesize flavin mono- nucleotide (FMN) and flavin adenine dinucleotide (FAD) used.
  • Panthothenate pantothenic acid, R- (+) -N- (2, 4-di-hydroxy-3, 3-dimethyl-l-oxobutyl) -ß-alanine
  • pantothenate biosynthesis consist of the ATP-driven condensation of ß-alanine and pantoic acid.
  • pantothenate The enzymes responsible for the biosynthetic steps for the conversion into pantoic acid, into ß-alanine and for the condensation into pantothenic acid are known.
  • the metabolically active form of pantothenate is coenzyme A, whose biosynthesis takes place over 5 enzymatic steps.
  • Pantothenate, pyridoxal-5'-phosphate, cysteine and ATP are the precursors of coenzyme A.
  • These enzymes not only catalyze the formation of pantothenate, but also the production of (R) -pantoic acid, (R) -pantolactone, (R ) -Panthenol (provitamin B 5 ), Pantethein (and its derivatives) and coenzyme A.
  • Lipoic acid is derived from octanoic acid and serves as a coenzyme in energy metabolism, where it becomes part of the pyruvate dehydrogenase complex and the ketoglutarate dehydrogenase complex.
  • Folates are a group of substances that are all derived from folic acid, which in turn is derived from L-glutamic acid, p-aminobenzoic acid and 6-methylpterine.
  • Corrinoids such as the cobalamines and especially vitamin B ⁇
  • the porphyrins belong to a group of chemicals that are characterized by a tetrapyrrole ring system.
  • the biosynthesis of vitamin B ⁇ 2 is sufficiently complex that it has not been fully characterized, but a large part of the enzymes and substrates involved is now known.
  • Nicotinic acid (nicotinate) and nicotinamide are pyridine derivatives, which are also known as "niacin”.
  • Niacin is the precursor of the important coenzymes NAD (Nicotina ariaenin dinucleotide) and NADP (Nicotinamide adenine dinucleotide phosphate) and their reduced forms.
  • nucleic acid molecules which comprise a nitrogen-containing base, a pentose sugar (for RNA, the sugar is ribose, for DNA, the sugar is D-deoxyribose) and phosphoric acid.
  • nucleoside encompasses molecules which serve as precursors of nucleotides, but which, in contrast to the nucleotides, have no phosphoric acid unit.
  • nucleotides that do not form nucleic acid molecules, but that serve as energy stores (i.e. AMP) or as coenzymes (i.e. FAD and NAD).
  • S-adenosyl-methionine, folate or riboflavin as an energy source for the cell (e.g. ATP or GTP) and for chemicals themselves, are usually used as flavor enhancers (e.g. IMP or GMP) or for many medical applications (see e.g. Kuninaka , A., (1996) "Nucleotides and Related Compounds in Biotechnology Vol. 6, Rehm et al., Ed. VCH: Weinheim, pp. 561-612).
  • Enzymes which are based on purine, pyrimidine, nucleoside or nucleotide metabolism are also increasingly serving as targets against which crop protection chemicals, including fungicides, herbicides and insecticides, are being developed.
  • the purine nucleotides are synthesized from ribose 5-phosphate via a series of steps via the intermediate compound inosine 5 'phosphate (IMP), which leads to the production of guanosine 5' monophosphate (GMP) or adenosine 5 'monophosphate (AMP ) leads from which the triphosphate forms used as nucleotides can be easily produced. These compounds are also used as energy stores so that their degradation provides energy for many different biochemical processes in the cell. Pyrimidine biosynthesis takes place via the formation of uridine 5 'monophosphate (UMP) from ribose 5-phosphate. UMP in turn is converted to cytidine 5 'triphosphate (CTP).
  • IMP intermediate compound inosine 5 'phosphate
  • AMP adenosine 5 'monophosphate
  • the deoxy forms of all nucleotides are produced in a one-step reduction reaction from the diphosphate ribose form of the nucleotide to the diphosphate deoxyribose for the nucleotide. After phosphorylation, these molecules can participate in DNA synthesis.
  • Trehalose consists of two glucose molecules that are linked together via an ⁇ , -1, 1 bond. It is commonly used in the food industry as a sweetener, as an additive for dried or frozen foods, and in beverages. However, it is also used in the pharmaceutical, cosmetics and biotechnology industries (see, e.g., Nishimoto et al., (1998) US Patent No. 5,759,610; Singer, MA and Lindquist, S. Trends Biotech. 16 (1998) 460-467; Paiva,
  • Trehalose is produced by enzymes from many microorganisms and is naturally released into the surrounding medium from which it can be obtained by methods known in the art.
  • ddh gene of C. glutamicum (Ishino et al. (1987) Nucleic Acids Res. 15, 3917), in particular a fragment at the 5 -terminal region of the ⁇ kodieren- amplify any sequence portion of the region with known methods by PCR and clone the resulting PCR product in pSLl ⁇ (Kim, YH & H.-S. Lee (1996) J. Microbiol. Biotechnol. 6, 315-320) to obtain the vector pSL18 ⁇ ddh.
  • Other vectors with a marker gene suitable for C. glutamicum can also be used for this. The procedure is familiar to the person skilled in the art.
  • the cgIIM gene can be expressed in a suitable E. coli strain (McrBC deficient (alternative name hsdRM deficient) such as NM522 or HB101) in different ways, both as a genomic copy and on plasmids.
  • McrBC deficient alternative name hsdRM deficient
  • One method is based on the use of the plasmid pTcl5AcglIM.
  • the plasmid pTcl5AcglIM comprises the origin of replication of the plasmid pl5A (Selzer et al. (1983) Cell 32, 119-129), a gene for resistance to tetracycline (Genbank Acc. No. J01749) and the cgIIM gene (Schäfer et al.
  • E. coli strains that carry pTcl5AcglIM have DNA that carries the cgllM methylation pattern. Accordingly, the pSLl8 derivatives (such as pSL18 ⁇ ddh, see above) are also "cgIIM-methylated”.
  • the plasmid DNA of the N 522 strain (pTcl5AcglIM / pSLl8 ⁇ ddh) can be obtained by customary methods (Sambrook, J. et al. (1989) "Molecular Cloning: A Laboratory Manual”. Cold Spring Harbor Laboratory Press or Ausubel, FM et al.
  • C. glutamicum ATCC13032 can be used, but other corynebacteria can also be used.
  • Plasmid pSLl ⁇ ddh obtained from an E. coli strain without pTcl5AcglIM did not lead to transformants after electroporation in any of our experiments.
  • pSLl ⁇ ddh obtained from a pTcl5AcglIM-carrying E. coli strain resulted in transformants being obtained by electroporation.
  • These transformants were clones in which the ddh gene was deactivated, as could be shown, for example, by a lack of Ddh activity. Ddh activity can be measured by known methods (see e.g. Misono et al. (1986) Agric. Biol. Chem. 50, 1329-1330).

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Abstract

L'invention concerne un procédé pour produire des corynebactéries contenant une ou plusieurs séquences génomiques modifiées, selon lequel on utilise un vecteur ne se répliquant pas dans les corynebactéries et dont l'acide nucléique n'est pas reconnu comme étranger par les corynebactéries.
EP01982319A 2000-09-20 2001-09-19 Procede pour modifier le genome de corynebacteries Withdrawn EP1322766A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP08075086A EP1921151A1 (fr) 2000-09-20 2001-09-19 Procédé de modification du génome de corynebactéries

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10046870A DE10046870A1 (de) 2000-09-20 2000-09-20 Verfahren zur Veränderung des Genoms von Corynebakterien
DE10046870 2000-09-20
PCT/EP2001/010805 WO2002024917A2 (fr) 2000-09-20 2001-09-19 Procede pour modifier le genome de corynebacteries

Related Child Applications (1)

Application Number Title Priority Date Filing Date
EP08075086A Division EP1921151A1 (fr) 2000-09-20 2001-09-19 Procédé de modification du génome de corynebactéries

Publications (1)

Publication Number Publication Date
EP1322766A2 true EP1322766A2 (fr) 2003-07-02

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ID=7657155

Family Applications (2)

Application Number Title Priority Date Filing Date
EP08075086A Withdrawn EP1921151A1 (fr) 2000-09-20 2001-09-19 Procédé de modification du génome de corynebactéries
EP01982319A Withdrawn EP1322766A2 (fr) 2000-09-20 2001-09-19 Procede pour modifier le genome de corynebacteries

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EP08075086A Withdrawn EP1921151A1 (fr) 2000-09-20 2001-09-19 Procédé de modification du génome de corynebactéries

Country Status (8)

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US (2) US20030170775A1 (fr)
EP (2) EP1921151A1 (fr)
JP (1) JP2004509625A (fr)
KR (1) KR20030074597A (fr)
AU (1) AU2002213937A1 (fr)
CA (1) CA2422743A1 (fr)
DE (1) DE10046870A1 (fr)
WO (1) WO2002024917A2 (fr)

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DE10222858A1 (de) 2002-05-23 2003-12-04 Basf Ag Verfahren zur fermentativen Herstellung schwefelhaltiger Feinchemikalien
DE10239073A1 (de) * 2002-08-26 2004-03-11 Basf Ag Verfahren zur fermentativen Herstellung schwefelhaltiger Feinchemikalien
DE10239082A1 (de) 2002-08-26 2004-03-04 Basf Ag Verfahren zur fermentativen Herstellung schwefelhaltiger Feinchemikalien
DE10239308A1 (de) 2002-08-27 2004-03-11 Basf Ag Verfahren zur fermentativen Herstellung von schwefelhaltigen Feinchemikalien
DE10359660A1 (de) 2003-12-18 2005-07-28 Basf Ag Psod-Expressionseinheiten
DE10359594A1 (de) 2003-12-18 2005-07-28 Basf Ag PEF-TU-Expressionseinheiten
MXPA06006759A (es) 2003-12-18 2006-09-04 Basf Ag Metodos para la preparacion de lisina por fermentacion de corynebacterium glutamicum.
DE10359595A1 (de) 2003-12-18 2005-07-28 Basf Ag Pgro-Expressionseinheiten
DE102004061846A1 (de) 2004-12-22 2006-07-13 Basf Ag Mehrfachpromotoren
KR100694427B1 (ko) * 2005-12-02 2007-03-12 씨제이 주식회사 코리네박테리움 속 미생물 및 이를 이용한 5'-이노신산의제조 방법
ES2539280T3 (es) 2006-10-24 2015-06-29 Basf Se Procedimiento de reducción de la expresión génica mediante el uso de codones modificado
WO2009007326A2 (fr) 2007-07-06 2009-01-15 Basf Se Procédé de préparation d'une solution de glucose aqueuse
KR100957689B1 (ko) * 2008-01-18 2010-05-12 씨제이제일제당 (주) 5'-구아노신 모노포스페이트 생산능이 향상된코리네박테리움 속 미생물 및 이를 이용한 5'-구아노신모노포스페이트의 생산방법
US9963709B2 (en) * 2012-09-14 2018-05-08 Uchicago Argonne, Llc Transformable Rhodobacter strains, method for producing transformable Rhodobacter strains
JP2019050731A (ja) * 2016-01-15 2019-04-04 三島光産株式会社 酸素発生型光合成を行う生物の増殖促進方法
CN111073841A (zh) * 2019-11-25 2020-04-28 华农（肇庆）生物产业技术研究院有限公司 一种可有效表达外源蛋白的棒状杆菌atcc 13032改良菌种以及构建方法
KR102706898B1 (ko) * 2022-06-07 2024-09-19 씨제이제일제당 주식회사 리보플라빈 생산능이 향상된 코리네박테리움 속 미생물 및 이를 이용한 리보플라빈을 생산하는 방법
KR102879056B1 (ko) * 2023-01-27 2025-10-30 씨제이제일제당 (주) 글루타미시박터 할로피토콜라 유래 판토에이트-베타-알라닌 리가아제의 활성이 강화된 미생물 및 이의 용도

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KR20030074597A (ko) 2003-09-19
US20080131942A1 (en) 2008-06-05
EP1921151A1 (fr) 2008-05-14
WO2002024917A2 (fr) 2002-03-28
CA2422743A1 (fr) 2003-03-18
US20030170775A1 (en) 2003-09-11
WO2002024917A3 (fr) 2002-06-27
AU2002213937A1 (en) 2002-04-02
DE10046870A1 (de) 2002-03-28

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