Journal
CURRENT OPINION IN STRUCTURAL BIOLOGY
Volume 22, Issue 4, Pages 406-412Publisher
CURRENT BIOLOGY LTD
DOI: 10.1016/j.sbi.2012.03.010
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Funding
- Defense Threat Reduction Agency (DTRA) of the US Department of Defense
- CounterACT Program of the US National Institutes Of Health
- Israel Science Foundation
- Willner Albert Foundation
- Blanche Foundation
- Jack Wolgin Foundation
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The field of directed evolution has progressed to the point where it is feasible to engineer enzymes for unnatural substrates and reactions with catalytic efficiencies and regio-specificity or stereo-specificity that rival those of natural enzymes. Here, we describe the conceptual and methodological advances that have enabled this progress. We address methodologies based on small libraries enriched with improved variants and carrying compensatory stabilizing mutations. Such libraries can be combined with low-throughput screens that provide high accuracy and directly target the desired substrate and reaction conditions, and thereby provide highly improved variants.
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