Enantioselective synthesis of (S)-3-cyano-5-methylhexanoic acid by a high DMSO concentration tolerable Arthrobacter sp. ZJB-09277
•A novel bioprocess for (S)-3-cyano-5-methyl hexanoic acid by esterase was reported.•Activity and selectivity of the esterase were affected by the alcohol moiety of esters.•E-value of the hydrolysis reaction was notably enhanced by addition of 50% DMSO.•The whole-cell catalysts showed strong tolerance against high DMSO concentration.
A novel biocatalytic route for (S)-3-cyano-5-methylhexanoic acid, the key chiral intermediate of pregabalin, was successfully developed using whole cells of newly isolated Arthrobacter sp. ZJB-09277. Kinetic resolution of a series of rac-3-cyano-5-methylhexanoic acid esters bearing a β-stereocenter indicated that steric effect of the leaving alcohol moiety played an important role in determining activity and enantioselectivity of Arthrobacter sp. ZJB-09277 esterase. Enantiomeric ratio of the esterase toward rac-3-cyano-5-methylhexanoic acid ethyl ester was significantly increased from 33 to 80 by addition of 50% (v/v) DMSO and key reaction parameters optimization. The whole-cell catalysts exhibited strong tolerance against high DMSO concentration up to 80% (v/v). Enzymatic resolution of the substrate at a concentration of 100 mM gave (S)-3-cyano-5-methylhexanoic acid in 44.6 mM and 95.1% ee, which greatly increased the feasibility of this bioprocess to become an industrial approach.
Journal: Biochemical Engineering Journal - Volume 83, 15 February 2014, Pages 97–103