Research Paper

Biotechnology and Bioprocess Engineering

, 16:625

First online:

Aminotransferase-catalyzed asymmetric synthesis of benazepril intermediate

  • Bum-Yeol HwangAffiliated withSchool of Chemical Engineering and Institute for Molecular Biology and Genetics, Seoul National UniversityDepartment of Chemical Engineering, QB3 Institute, University of California-Berkeley
  • , Minho ChaAffiliated withSchool of Chemical Engineering and Institute for Molecular Biology and Genetics, Seoul National University
  • , Hyung-Yeon ParkAffiliated withSchool of Chemical Engineering and Institute for Molecular Biology and Genetics, Seoul National University
  • , Byung-Gee KimAffiliated withSchool of Chemical Engineering and Institute for Molecular Biology and Genetics, Seoul National University Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

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