Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Stereoselective Bioreduction of Ethyl 3-Oxo-3-(2-Thienyl) Propanoate Using the Short-Chain Dehydrogenase/Reductase ChKRED12

  • Ren, Zhi-Qiang (Key Laboratory of Environmental and Applied Microbiology, Chengdu Institute of Biology, Chinese Academy of Sciences) ;
  • Liu, Yan (Key Laboratory of Environmental and Applied Microbiology, Chengdu Institute of Biology, Chinese Academy of Sciences) ;
  • Pei, Xiao-Qiong (Key Laboratory of Environmental and Applied Microbiology, Chengdu Institute of Biology, Chinese Academy of Sciences) ;
  • Wu, Zhong-Liu (Key Laboratory of Environmental and Applied Microbiology, Chengdu Institute of Biology, Chinese Academy of Sciences)
  • Received : 2018.04.30
  • Accepted : 2018.07.31
  • Published : 2019.11.28
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Abstract

Ethyl (S)-3-hydroxy-3-(2-thienyl) propanoate ((S)-HEES) acts as a key chiral intermediate for the blockbuster antidepressant drug duloxetine, which can be achieved via the stereoselective bioreduction of ethyl 3-oxo-3-(2-thienyl) propanoate (KEES) that contains a 3-oxoacyl structure. The sequences of the short-chain dehydrogenase/reductases from Chryseobacterium sp. CA49 were analyzed, and the putative 3-oxoacyl-acyl-carrier-protein reductase, ChKRED12, was able to stereoselectively catalyze the NADPH-dependent reduction to produce (S)-HEES. The reductase activity of ChKRED12 towards other substrates with 3-oxoacyl structure were confirmed with excellent stereoselectivity (>99% enantiomeric excess) in most cases. When coupled with a cofactor recycling system using glucose dehydrogenase, the ChKRED12 was able to catalyze the complete conversion of 100 g/l KEES within 12 h, yielding the enantiopure product with >99% ee, showing a remarkable potential to produce (S)-HEES.

Keywords

References

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