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

Humicola lanuginosa lipase was used for enantioselective hydrolyses of a se ries of homologous 2-phenoxyalkanoic acid ethyl esters. The enantioselectiv ity (E-value) of the enzyme changed from an (R)-enantiomer preference for t he smallest substrate, 2-phenoxypropanoic acid ester, to an (S)-enantiomer preference for the homologous esters with longer acyl moieties. The E-value s span the range from E=13 (R) to E=56 (S). A molecular modeling study iden tified two different substrate-binding modes for each enantiomer. We found that the enantiomers favored different modes. This discovery provided a mod el that offered a rational explanation for the observed switch in enantiose lectivity. (C) 1999 Elsevier Science Ltd. All rights reserved.