Increased amounts of substances by modifying a microorganism to

Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Preparing alpha or beta amino acid or substituted amino acid...

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Details

424 932, 435115, 4352521, 43525233, 435849, 435108, 435110, 435116, A01N 6300, C12P 1304, C12N 100, C12N 120

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058307168

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD

The present invention relates to a method for producing a target substance using a microorganism. Typical examples of the microorganism used in the present invention include microorganisms belonging to the genus Escherichia and coryneform bacteria, which have conventionally been used for production of various substances. Target substances produced herein include L-amino acids, antibiotics, vitamins, growth factors, physiologically active substances, and other substances generally produced by microorganisms. The present application discloses the method which improves the productivity of a final target substance in the process of producing the target substance using microorganisms.


BACKGROUND ART

L-amino acid fermentation is typically exemplified as a well known method for producing a target substance using microorganisms. L-amino acids are used not only for spices and foods but also as components of various medical nutrient mixtures, additives of animal feed, agents in pharmaceutical and chemical industries, further, growth factors for production of L-amino acids such as L-lysine and L-homoserine using microorganisms. Coryneform bacteria, microorganisms belonging to the genera Escherichia, Bacillus and Serratia and the like are known as microorganisms can be used for fermentation production of L-amino acid.
Wild type bacteria (wild type strains), auxotrophic strains induced from wild type strains, metabolic regulatory mutants induced from wild type strains as various drug resistant mutants, and strains having properties of both auxotrophic strains and metabolic regulatory mutants may be used for fermentation production of L-amino acids. Substances required for the auxotrophic strains vary from strain to strain, and auxotrophic strains which require the identical substance varied in degree of those auxotrophy. Similarly, the metabolic regulatory mutants obtained as various drug resistant mutants have diversities.
Recombinant DNA technology has recently been used for L-amino acid fermentation. The theory of this technology is based on enhancement of an L-amino acid biosynthetic system in a host microorganism through enrichment of a gene(s) coding for an L-amino acid biosynthetic enzyme(s). Details of such technology are described in, for example, "Amino Acid Fermentation, Society Press Japan (1986)"
However, the microorganisms conventionally used in fermentation production of L-amino acids have biosynthetic pathways including L-amino acid biosynthetic pathways and coenzyme biosynthetic pathways, identical with those of wild type microorganisms. The L-amino acid-producing microorganisms have been bred by desensitization of inhibition by a final product or the like existing in the L-amino acid biosynthetic pathway. For means to achieve such a breeding, for example, providing auxotrophic properties or drug resistance to cell of microorganism, or amplifying a gene(s) coding for biosynthetic enzyme(s) by recombinant DNA technology have been applied.
A lot of substances other than L-amino acids can be produced through fermentation using microorganisms. As examples of such substances, antibiotics and vitamins are exemplified. There are various kind of antibiotics and a variety of materials are used as precursors of biosyntheses of such antibiotics. For example, sugars, amino acids, acetic acid, propionic acid and mevalonic acid are used. A target antibiotic is produced from such a precursor through conversion process of various metabolites other than the precursor. The same mechanism is observed in vitamins and other biogenic substances.
In production of aforementioned substances using microorganisms, each substance is produced in a biosynthetic pathway in the cell of microorganism. One of the important coenzymes essential for effective function of responsible enzymes in the biosynthetic system is reduced nicotinamide adenine dinucleotide phosphate (hereinafter may be referred to as NADPH). However, relationship between NADPH and production of substances using microorganisms have not been reporte

REFERENCES:
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Database WPI, Week 2584, Derwent Publications Ltd., London, GB, AN 84-155419, XP002060859, "Sorbitol Prepn. Using Yeast of Pichia Genus--by Culturing Yeast in Medium Contg. Pentose, and Reacting Glucose with Opt. Treated Yeast Presence of NADPH" Agency of Ind. Sci. & Technology, May 11, 1984.
Adam Jaworski et al, "Transformation of Steroids by Fungal Spores", Eur. J. Appl. Microbiol. Biotechnol, vol. 16, pp. 63-69, 1982.
Brigitte Dauce-Le Reverend, et al. European J. Appli. Microbiol. Bitotechnol. (1982) 15, pp. 227-231.
Biochemistry, 3.sup.rd Edition, Zubay p. 579 W.M. Brown Publishers, 1993.

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