Empirical Biocatalyst Engineering: Escaping the Tyranny of High

Chapter 3

Empirical Biocatalyst Engineering: Escaping the Tyranny of High-Throughput Screening

Downloaded by UNIV OF CALIFORNIA SANTA BARBARA on June 16, 2016 | http://pubs.acs.org Publication Date: February 15, 2005 | doi: 10.1021/bk-2005-0900.ch003

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Jon E. Ness , Tony Cox , Sridhar Govindarajan , Claes Gustafsson , Richard A. Gross , and Jeremy Minshull 2

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DNA 2.0, 1455 Adams Drive, Menlo Park, C A 94025 N S F I / U C R C for Biocatalysis and Bioprocessing of Macromolecules, Polytechnic University, 6 Metrotech Center, Brooklyn, NY 11201

High throughput assays are a commonly used tool in empirical protein engineering. Such screens often do not accurately predict the behavior of proteins, including biocatalysts, under commercially relevant conditions. We are developing an alternative approach based on mathematical data-mining tools that allow us to determine sequence-activity relationships for proteins. Sequence-activity relationships can be used in the design of proteins with specified properties. The availability of methods to quickly synthesize designed sets of proteins make this a cost-effective technique for biocatalyst engineering. Because only small numbers ofvariants(