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Aminotransferase-catalyzed asymmetric synthesis of benazepril intermediate

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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.

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Authors and Affiliations

  1. School of Chemical Engineering and Institute for Molecular Biology and Genetics, Seoul National University, Seoul, 151-742, Korea

    Bum-Yeol Hwang, Minho Cha, Hyung-Yeon Park & Byung-Gee Kim

  2. Department of Chemical Engineering, QB3 Institute, University of California-Berkeley, CA, 94720-3220, Berkeley, USA

    Bum-Yeol Hwang

Authors
  1. Bum-Yeol Hwang
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  2. Minho Cha
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  3. Hyung-Yeon Park
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  4. Byung-Gee Kim
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Correspondence to Byung-Gee Kim.

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Hwang, BY., Cha, M., Park, HY. et al. Aminotransferase-catalyzed asymmetric synthesis of benazepril intermediate. Biotechnol Bioproc E 16, 625–630 (2011). https://doi.org/10.1007/s12257-011-0066-y

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  • DOI: https://doi.org/10.1007/s12257-011-0066-y

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