Flexibility of Lipase Brought About by Solvent Effects Controls Its Enantioselectivity in Organic Media

The behavior of the enantioselectivity of Candida rugosa lipase was investigated in the esterification of 2-(4-substituted phenoxy)propionic acids with 1-butanol in aliphatic, aromatic, and ethereal solvents. The observed enantioselectivity (E value) was greatly affected by the solvent nature. Two key solvent characteristics, dielectric constant ((epsilon)) and hydrophobicity (log P), failed to explain the solvent effects on the E value. On the other hand, the variation of the E value was found to be successfully correlated with the lipase flexibility brought about by the solvent effects, the flexibility of which was estimated by the ESR measurements of the spinlabeled lipase. Although organic chemists should often undertake a solvent screening step in the biocatalytic asymmetric resolutions, the obtained correlation will provide a useful guide in the solvent optimization step.