Ampicillin Synthesis Using a Two-Enzyme Cascade with Both α-Amino Ester Hydrolase and Penicillin G Acylase

被引:14
作者
Blum, Janna K. [1 ]
Deaguero, Andria L. [1 ]
Perez, Carolina V. [1 ]
Bommarius, Andreas S. [1 ,2 ]
机构
[1] Parker H Petit Inst Bioengn & Biosci, Sch Chem & Biomol Engn, Atlanta, GA 30332 USA
[2] Georgia Inst Technol, Sch Chem & Biochem, Atlanta, GA 30332 USA
关键词
amino esters; antibiotics; enzyme catalysis; hydrolases; lactams; BETA-LACTAM ANTIBIOTICS; 3 CONSECUTIVE BIOTRANSFORMATIONS; FULLY AQUEOUS-MEDIUM; ACETOBACTER-TURBIDANS; XANTHOMONAS-CITRI; SUBSTRATE-SPECIFICITY; ENZYMATIC-SYNTHESIS; CEFAZOLIN; CATALYSIS;
D O I
10.1002/cctc.201000135
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
The current enzymatic production of semisynthetic beta-lactam antibiotics requires isolation and purification of the intermediate 6-aminopenicillanic acid which adds cost and complexity to the manufacturing process. In this work, we took advantage of the unique substrate specificity of a-amino ester hydrolases to perform a purely aqueous one-pot production of ampicillin from penicillin G and D-phenylglycine methyl ester, catalyzed by a-amino ester hydrolase and penicillin G acylase. The synthesis was performed in both a one-pot, one-step synthesis resulting in a maximum conversion of 39%, and a one-pot, two-step process resulting in a maximum conversion of 47%. The two-enzyme cascade reported in this paper is a promising alternative to the current enzymatic two-step, two-pot manufacturing process for semisynthetic beta-lactam antibiotics which requires intermittent isolation of 6-aminopenicillanic acid.
引用
收藏
页码:987 / 991
页数:5
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