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Published February 2009 | Accepted Version
Journal Article Open

Directed enzyme evolution: climbing fitness peaks one amino acid at a time

Abstract

Directed evolution can generate a remarkable range of new enzyme properties. Alternate substrate specificities and reaction selectivities are readily accessible in enzymes from families that are naturally functionally diverse. Activities on new substrates can be obtained by improving variants with broadened specificities or by step-wise evolution through a sequence of more and more challenging substrates. Evolution of highly specific enzymes has been demonstrated, even with positive selection alone. It is apparent that many solutions exist for any given problem, and there are often many paths that lead uphill, one step at a time.

Additional Information

© 2009 Elsevier. Available online 25 February 2009. CAT was supported by Ruth M Kirschstein National Research Service Award F32 GM076964 and NIH grant R01 GM074712-01A1. We also acknowledge support from the Institute for Collaborative Biotechnologies, the Jacobs Institute for Molecular Medicine, and the Department of Energy.

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