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Directed Evolution of Protein Catalysts

Authors
  • Zeymer, Cathleen
  • Hilvert, Donald
Type
Published Article
Journal
Annual Review of Biochemistry
Publisher
Annual Reviews
Publication Date
Jun 20, 2018
Volume
87
Pages
131–157
Identifiers
DOI: 10.1146/annurev-biochem-062917-012034
Source
Annual Reviews
Keywords
License
Yellow

Abstract

Directed evolution is a powerful technique for generating tailor-made enzymes for a wide range of biocatalytic applications. Following the principles of natural evolution, iterative cycles of mutagenesis and screening or selection are applied to modify protein properties, enhance catalytic activities, or develop completely new protein catalysts for non-natural chemical transformations. This review briefly surveys the experimental methods used to generate genetic diversity and screen or select for improved enzyme variants. Emphasis is placed on a key challenge, namely how to generate novel catalytic activities that expand the scope of natural reactions. Two particularly effective strategies, exploiting catalytic promiscuity and rational design, are illustrated by representative examples of successfully evolved enzymes. Opportunities for extending these approaches to more complex biocatalytic systems are also considered.

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