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Asymmetric synthesis of tert-butyl (3R,5S)-6-chloro-3,5-dihydroxyhexanoate using a self-sufficient biocatalyst based on carbonyl reductase and cofactor co-immobilization

  • Xiao-Jian Zhang
  • Wen-Zhong Wang
  • Rong Zhou
  • Zhi-Qiang LiuEmail author
  • Yu-Guo Zheng
Research Paper
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Abstract

tert-Butyl (3R,5S)-6-chloro-3,5-dihydroxyhexanoate [(3R,5S)-CDHH] is the key chiral intermediate to synthesize the side chain of the lipid-lowering drug rosuvastatin. Carbonyl reductases showed excellent activity for the biosynthesis of (3R,5S)-CDHH. The requirement of cofactor NADH/NADPH leads to high cost for the industrial application of carbonyl reductases. In this study, a self-sufficient biocatalyst based on carbonyl reductase and NADP+ co-immobilization strategy was developed on an amino resin carrier LX-1000HAA (SCR-NADP+@LX-1000HAA). The self-sufficient biocatalyst achieved in situ cofactor regeneration and showed the activity recovery of 77.93% and the specific activity of 70.45 U/g. Asymmetric synthesis of (3R,5S)-CDHH using SCR-NADP+@LX-1000HAA showed high enantioselectivity (> 99% e.e.) and yield (98.54%). Batch reactions were performed for ten cycles without extra addition of NADP+, and the total yield of (3R,5S)-CDHH achieved at 10.56 g/g biocatalyst. The present work demonstrated the potential of the self-sufficient biocatalyst for the asymmetric biosynthesis of rosuvastatin intermediate.

Graphic abstract

Keywords

Carbonyl reductase NADPH Self-sufficient biocatalyst Asymmetric synthesis tert-Butyl (3R,5S)-6-chloro-3,5-dihydroxyhexanoate 
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Notes

Acknowledgements

This work was financially supported by the Natural Science Foundation of China (no. 21672190).

Compliance with ethical standards

Conflict of interest

We declare that we have no conflict of interest.

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© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and BioengineeringZhejiang University of TechnologyHangzhouChina

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