Solvent effects in non-aqueous biocatalysis

Enzymes are extraordinary catalysts not only satisfying the needs of living organisms, but also exhibiting catalytic activity in unnatural non-aqueous environment. This opens a path for exploiting them in technological applications and carrying out new reactions. The change of a reaction medium significantly alters enzyme activity or enantioselectivity, but the underlying molecular explanation is missing. This proposal focuses on elucidating the dependence of enantioselectivity on the composition of a mixed solvent for transesterification catalyzed by Candida antarctica lipase B which will be investigated by ab initio calculations, coupled valence bond state description and classical molecular dynamics simulations with enhanced sampling techniques. At first, the detailed nature of the rate-limiting step of the reaction will be revealed. Then, the effect of solvent composition on the behavior of the most important reaction intermediate and on the actual reaction will be explored. Gained molecular level insight will provide guidelines for rational optimization of reaction conditions.