Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Preparing alpha or beta amino acid or substituted amino acid...
Patent
1997-09-22
1999-05-25
Lilling, Herbert J.
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Preparing alpha or beta amino acid or substituted amino acid...
435850, C12P 1304, C12N 120
Patent
active
059069279
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a process for producing L-2-aminoadipic acid by utilizing microorganisms. L-2-Aminoadipic acid is a nonprotein amino acid and it is usable as a valuable intermediate for medicines such as a methotrexate derivative (WO 92/09436) effective as an antirheumatic drug, remedy for psoriasis and carcinostatic agent. This compound is also usable as a terminal-modifying agent for physiologically active peptides such as peptide antibiotics and peptide hormones and as a precursor in the fermentative production of .beta.-lactam antibiotics typified by penicillins and cephalosporins.
BACKGROUND OF THE INVENTION
L-2-Aminoadipic acid is found widely in the biological field including Cholera vibrio which is a bacterium, vegetables typified by corns and frog embryos. Further, L-2-aminoadipic acid also holds a position of an intermediate in the biosynthesis of lysine with eukaryotic microorganisms or of a precursor in the biosynthesis of .beta.-lactam antibiotics. The chemical synthesis of L-2-aminoadipic acid is not yet an effective means from the viewpoint of the cost, since an optical resolution and multi-stage reactions are necessitated. As for the production of L-2-aminoadipic acid with microorganisms, a process wherein this acid is produced from L-pipecolic acid with a microorganism of Alcaligenes, (hereinafter referred to as "J. P. KOKAI") No. Hei 1-98495! and there is also known a process wherein it is produced from L-lysine with a microorganism of Agrobacterium, Klebsiella, Alcaligenes, Brevibacterium or Bacillus (J. P. KOKAI No. Hei 6-181787). However, these two processes have problems when they are to be employed for the mass production. Namely, starting L-pipecolic acid is expensive in the former process and the reaction efficiency is usually low in the latter process.
DISCLOSURE OF THE INVENTION
The object of the present invention is to provide a microbial process for the mass production L-2-aminoadipic acid directly from L-lysine in a high yield.
The present invention has been completed on the basis of a finding that L-2-aminoadipic acid can be directly and efficiently obtained from L-lysine by using a microorganism of a specified genus capable of converting an aminomethyl group into carboxyl group by the oxidation without modifying the .alpha.-amino group of the lysine.
Namely, the present invention provides a process for producing L-2-aminoadipic acid, which comprises the step of converting an aminomethyl group of L-lysine into a carboxyl group by use of a culture of a microorganism of the genus Flavobacterium.
BEST MODE FOR CARRYING OUT THE INVENTION
L-2-Aminoadipic acid produced by the process of the present invention is represented by the following formula 1: described above.
The salts include salts of L-2-aminoadipic acid with organic acids such as acetic acid and tartaric acid; inorganic acids such as hydrochloric acid and sulfuric acid; organic bases such as triethylamine and N-methylmorpholine; and inorganic bases such as sodium hydroxide and potassium hydroxide.
The microorganism of the genus Flavobacterium usable in the present invention may be that of any strain of the genus Flavobacterium so far as it is capable of converting the aminomethyl group of lysine into carboxyl group by the oxidation to directly form L-2-aminoadipic acid from lysine. A preferred example thereof is a bacterium of No. 7-1 strain of the genus Flavobacterium which is obtained from the soil. The No. 7-1 strain is deposited with the National Institute of Bioscience and Human-Technology Agency of Industrial Science and Technology, the Ministry of International Trade and Industry (address: 1-3, Higashi 1-chome, Tsukuba-shi, Ibaraki-ken, Japan) under FERM BP-5457 (Flavobacterium sp. 7-1; deposition date: Jan. 17, 1995).
The No. 7-1 strain is a gram-negative, aerobic bacillus having a cell width of 0.5 .mu.m and length of 2 .mu.m, which forms no endospores and which is positive to catalase, oxidase and phosphatase and secretes a yellow pigment. This strain is free from flag
REFERENCES:
Kenji Soda et al, "L-Lysine--.alpha.-Ketoglutarate Aminotransferase. I. Identification of a Product, .increment..sup.1 -Piperideine-6-carboxylic Acid", Biochemistry, 7(11)4102-4109, 1968.
Soda et al, "L-Lysine--.alpha.-Ketoglutarate Aminotransferase. II. Purification, Crystallization, and Properties", Biochemistry, 7(11)4110-4119, 1968.
Soda et al, "Studies on Transamination in Microorganisms, Part III. L-Lysine--.alpha.-Ketoglutarate Acid Transaminase Reaction", Agr. Biol. Chem., 25(11)811-819, 1961.
APS Abstract of Japanese Patent 06-181787 Nakayama, Jul. 5, 1994.
APS Abstract of Japanese Patent 60-160889 Yokozeki et al, Aug. 22, 1985.
Biosis Abstract 80:247113 Kern et al "Antimicrob Agents Chemother" 17(4) 1980 pp. 679-685, 1980.
Nakata Kuniho
Narita Takao
Tsunekawa Hiroshi
Yoshioka Takeo
Chugai Seiyaku Kabushiki Kaisha
Lilling Herbert J.
Mercian Corporation
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