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Abstract

With the advent of directed evolution of stereoselective enzymes almost 20 years ago and the rapid development of this exciting area of research, the traditional limitations of biocatalysts in organic chemistry have been eliminated. It is now possible to enhance or invert enantioselectivity, broaden the substrate scope and increase the activity of many different types of enzymes. In addition to providing a prolific source of catalysts for asymmetric transformations, many lessons can be learned from directed evolution on the molecular level, because stereoselectivity is a sensitive probe. This review focuses on two types of lessons arising from studies focusing on (1) uncovering the source of altered stereoselectivity, and (2) constructing fitness landscapes which reveal additive and non-additive mutational effects as well as ways to escape from local minima. Case studies featuring enzymes of the type epoxide hydrolase, lipase and Baeyer–Villiger monooxygenase are presented.