Abstract
The use of Candida antarctica lipase B and lipases from Candida rugosa and Rhizomucor miehei for kinetic resolutions is discussed. Theories and methods for molecular modelling are presented briefly. We have studied the transition state geometry in acyl transfer reactions of serine hydrolases by ab initio calculations of proton transfer mechanisms in ester hydrolysis in order to be able to predict enantioselectivity by means of molecular modelling. A combination of molecular modelling and kinetic studies was used to construct models that explain and predict the enantioselectivity of these lipases. The calculations and the experimental results provide support for a proposal that enantiomers can bind in different orientations. Structural factors of importance for the enantioselectivity have been idenified. Our results provide information on the scope and limitations of the use of these enzymes in asymmetric synthesis. Molecular modelling also provides information about possible genetic modifications of the enzymes in order obtain a useful catalyst for a specific enantioselective transformation or for the use of the lipase framework and part of the catalytic site for the catalysis of unnatural reactions.
