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Enzymatic preparation of t-butyl-6-cyano-(3R, 5R)-dihydroxyhexanoate by a whole-cell biocatalyst co-expressing carbonyl reductase and glucose dehydrogenase

Paper ID Volume ID Publish Year Pages File Format Full-Text
34478 45027 2015 7 PDF Available
Title
Enzymatic preparation of t-butyl-6-cyano-(3R, 5R)-dihydroxyhexanoate by a whole-cell biocatalyst co-expressing carbonyl reductase and glucose dehydrogenase
Abstract

•Co-expression of carbonyl reductase and glucose dehydrogenase was achieved in a favorable order.•Exogenous addition of cofactors was completely eliminated for the bioreduction.•Whole-cell based biocatalytic process was established for the preparation of statin side chains.

Statins are the most effective drugs for hyperlipidemia-related diseases by competitively inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase. Because of the difficulty and environmental concerns associated with chemical preparation of the chiral diols of statin side chains, different biocatalytic approaches have been explored and the two-step bio-reduction process for the introduction of two chiral hydroxyl groups has been industrialized. However, the high costs and poor stability of nicotinamide cofactors in the process was a major limiting factor. In the present study, a whole-cell biocatalyst simultaneously expressing carbonyl reductase and glucose dehydrogenase was constructed. This biocatalyst was then used to synthesize t-butyl-6-cyano-(3R, 5R)-dihydroxyhexanoate via enzymatic reduction of t-butyl-6-cyano-(5R)-hydroxy-3-carboxylhexanoate, which involves in the self-recycling of endogenous cofactors. After systematic optimization, the bioconversion was complete with a productivity of 120 g l−1 day−1 without exogenous addition of cofactors after 7 h at 35 g/L substrate concentration. Thus, the present system has simplified the process and improved the overall efficiency for the preparation of statin side chains.

Keywords
Carbonyl reductase; Glucose dehydrogenase; Nicotinamide cofactor; Whole-cell biocatalysis; Statin side chains
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Enzymatic preparation of t-butyl-6-cyano-(3R, 5R)-dihydroxyhexanoate by a whole-cell biocatalyst co-expressing carbonyl reductase and glucose dehydrogenase
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Publisher
Database: Elsevier - ScienceDirect
Journal: Process Biochemistry - Volume 50, Issue 1, January 2015, Pages 104–110
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us