On the role of Transition-State Substrate Desolvation in Enzymatic Enantioselectivity in Aqueous-Organic Mixtures

Publisher Website
Google Scholar
Abstract
We previously found that the observed solvent dependence of enzymatic enantioselectivity in organic media could be almost quantitatively explained on the basis of the energetics of substrate desolvation upon formation of enzyme-bound transition states. In the present study, we have expanded this thermodynamic treatment to predominantly aqueous media and analyzed two recent literature reports on the variation of lipase enantioselectivity by the addition of organic cosolvents. Our analysis has revealed that in neither case can the energetics of substrate desolvation significantly contribute to the experimentally observed changes in the enantioselectivity of lipases. Therefore other factors, e.g., cosolvent-induced conformational changes in enzyme molecules or differential solvent displacement from the enzyme active center by the substrate, must be at play.