A new mechanism of enantioselectivity toward chiral primary alcohol by lipase from Pseudomonas cepacia

The stereo-recognition of chiral primary alcohols by lipase from Pseudomonas cepacia was found to deviate from earlier observations. Enantioselectivity toward 14 pairs of chiral primary alcohol esters by this lipase was dependent on the existence of an Onon-alpha (oxygen at non-alpha-position of the acyloxy group) in the alcohol moiety, and decreased as the size of the acyl moiety increased. Chemical modification on the lipase and molecular dynamics simulations indicated that Tyr(29) located within the catalytic cavity forms a hydrogen bond with the Onon-alpha of the preferred enantiomer of the primary alcohol ester. However, a larger acyl moiety suffered stronger hindrance from the catalytic cavity wall of the lipase, pushing the Onon-alpha away from Tyr(29), and thus weakening the stereo-recognition. (C) 2014 Elsevier B.V. All rights reserved.