Aminotransferase-catalyzed asymmetric synthesis of benazepril intermediate

  • Bum-Yeol Hwang
  • Minho Cha
  • Hyung-Yeon Park
  • Byung-Gee Kim
Research Paper

Abstract

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 α-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.

Keywords

aminotransferase benazepril product inhibition reaction coupling docking simulation 

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Copyright information

© The Korean Society for Biotechnology and Bioengineering and Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  • Bum-Yeol Hwang
    • 1
    • 2
  • Minho Cha
    • 1
  • Hyung-Yeon Park
    • 1
  • Byung-Gee Kim
    • 1
  1. 1.School of Chemical Engineering and Institute for Molecular Biology and GeneticsSeoul National UniversitySeoulKorea
  2. 2.Department of Chemical Engineering, QB3 InstituteUniversity of California-BerkeleyBerkeleyUSA

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