Abstract
Ethyl (S)-4-chloro-3-hydroxybutanoate ester ((S)-CHBE) is a precursor of enantiopure intermediates used for the production of chiral drugs, including the cholesterol-lowering 3-hydroxy-3-methyl-glutaryl CoA reductase inhibitors (statins). The asymmetric reduction of ethyl 4-chloro-3-oxobutanoate ester (COBE) to (S)-CHBE by biocatalysis has several positive attributes, including low cost, mild reaction conditions, high yield, and a high level of enantioselectivity. During genome database mining of the yeast Pichia stipitis, our group found two novel carbonyl reductases (PsCRI and PsCRII) that have a promising future for the industrial production of (S)-CHBE with >99% enantiomeric excess. This review covers the main process of biosynthesis of (S)-CHBE: screening of microorganisms that catalyze the reduction of COBE to (S)-CHBE (I); gene cloning, expression, and characterization of carbonyl reductases for the production of (S)-CHBE in Escherichia coli (II); development of cofactor generation systems for regenerating cofactors (III); and biocatalysis of COBE to (S)-CHBE by recombinant E. coli (IV).
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Acknowledgements
This work was supported by the Major Basic Research Program of China (grant no. 2009CB724700) and the National Key Technology RD Program (grant no. 2008BAI63B07). Hanjie Ying was supported by the China National Funds for Distinguished Young Scientists (grant no. 21025625). Qi YE was supported by the Innovation Fund for Doctoral Dissertation of Nanjing University of Technology (BSCX200911). We also thank Prof. Ming Yan, Jian Xiong, and Lin Xu for revising the paper.
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Ye, Q., Ouyang, P. & Ying, H. A review—biosynthesis of optically pure ethyl (S)-4-chloro-3-hydroxybutanoate ester: recent advances and future perspectives. Appl Microbiol Biotechnol 89, 513–522 (2011). https://doi.org/10.1007/s00253-010-2942-3
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DOI: https://doi.org/10.1007/s00253-010-2942-3