Aminotransferase-catalyzed Asymmetric Synthesis of Benazepril Intermediate

作者：Hwang Bum Yeol^*; Cha Minho; Park Hyung Yeon; Kim Byung Gee

来源：Biotechnology and Bioprocess Engineering, 2011, 16(4): 625-630.

DOI：10.1007/s12257-011-0066-y

• aminotransferase
• benazepril
• product inhibition
• reaction coupling
• docking simulation

Benazepril is a medication used to treat hypertension, congestive heart failure and chronic renal failures. A benazepril intermediate was synthesized through asymmetric synthesis using aromatic aminotransferase from Enterobacter sp. BK2K-1 (AroATEs). Sodium 4-methoxy-4-(2-nitrophenyl)-2-oxobutanoate (1) and (E)-4-(2-nitrophenyl)-2-oxobut-3-enoic acid (2) were tested as amino acceptors for the transamination by AroATEs. The AroATEs showed higher activity towards 1, which could be explained using a docking simulation. Both the substrate and product inhibitions for the reaction of 1 as an amino acceptor and L-glutamate as an amino donor were examined. The product inhibition by alpha-ketoglutarate was able to be solved by the removal of the product using the glutamate dehydrogenase (GDH) and formate dehydrogenase (FDH) coupling system. Using 50 mM of 1, above 99% conversion (> 99% ee) was achieved using the AroATEs, with the GDH and FDH combined system.

• 出版日期2011-8