1. A review-biosynthesis of optically pure ethyl ( S)-4-chloro-3-hydroxybutanoate ester: recent advances and future perspectives.
- Author
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Qi Ye, Pingkai Ouyang, and Hanjie Ying
- Subjects
ESTERS ,BIOSYNTHESIS ,CHIRAL drugs ,PICHIA ,CARBONYL reductase ,MOLECULAR cloning - 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). [ABSTRACT FROM AUTHOR]
- Published
- 2011
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