Switched enantiopreference of Humicola lipase for 2-phenoxyalkanoic acid ester homologs can be rationalized by different substrate binding modes

Abstract

Humicola lanuginosa lipase was used for enantioselective hydrolyses of a series of homologous 2-phenoxyalkanoic acid ethyl esters. The enantioselectivity ( E-value) of the enzyme changed from an ( R)-enantiomer preference for the smallest substrate, 2-phenoxypropanoic acid ester, to an ( S)-enantiomer preference for the homologous esters with longer acyl moieties. The E-values span the range from E=13 ( R) to E=56 ( S). A molecular modeling study identified two different substrate-binding modes for each enantiomer. We found that the enantiomers favored different modes. This discovery provided a model that offered a rational explanation for the observed switch in enantioselectivity.