2-STEP IMMOBILIZED ENZYME CONVERSION OF CEPHALOSPORIN-C TO 7-AMINOCEPHALOSPORANIC ACID

被引:53
作者
CONLON, HD
BAQAI, J
BAKER, K
SHEN, YQ
WONG, BL
NOILES, R
RAUSCH, CW
机构
[1] Biopure Corporation, Cambridge, Massachusetts, 02141
关键词
CEPHALOSPORIN C; PRODUCTION OF 7ACA; IMMOBILIZED D-AMINO ACID OXIDASE; IMMOBILIZED GL-ACYLASE; INDUSTRIAL ENZYME PROCESS;
D O I
10.1002/bit.260460603
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The first large-scale production of 7-aminocephalosporanic acid (7ACA) from cephalosporin C (CPC) using a wholly enzymatic synthesis method is reported here. We produced 7ACA from CPC in as high a molar yield as 85% using the immobilized enzymes D-amino acid oxidase (D-AOD) and glutaryl-7-ACA acylase (GL-acylase). In the first reactor, CPC is converted to keto-adipyl-7-aminocephalosporanic acid (keto-7ACA) using an immobilized D-AOD isolated from a yeast, Trigonopsis variabilis. The keto-7ACA is then spontaneously converted to glutaryl-7-aminocephalosporanic acid (GL-7ACA) via a chemical reaction with hydrogen peroxide. The hydrogen peroxide is also a product of the D-AOD reaction. Near quantitative conversion of the keto-7ACA to GL-7ACA was observed. The second reactor converts GL-7ACA to 7ACA using an immobilized GL-acylase, which was isolated from a recombinant Escherichia coli. The final 7ACA crystalline product is a high quality product. The reactions are conducted under very mild aqueous conditions: pH 8.0 and 20 degrees to 25 degrees C. The production of desacetyl side products is minimal. This process is currently being implemented on an industrial scale to produce 7ACA. (C) 1995 John Wiley & Sons, Inc.
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页码:510 / 513
页数:4
相关论文
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