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Optimizing non-natural protein function with directed evolution

Brustad, Eric M. and Arnold, Frances H. (2011) Optimizing non-natural protein function with directed evolution. Current Opinion in Chemical Biology, 15 (2). pp. 201-210. ISSN 1367-5931. PMCID PMC3080047. doi:10.1016/j.cbpa.2010.11.020.

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Developing technologies such as unnatural amino acid mutagenesis, non-natural cofactor engineering, and computational design are generating proteins with novel functions; these proteins, however, often do not reach performance targets and would benefit from further optimization. Evolutionary methods can complement these approaches: recent work combining unnatural amino acid mutagenesis and phage selection has created useful proteins of novel composition. Weak initial activity in a computationally designed enzyme has been improved by iterative rounds of mutagenesis and screening. A marriage of ingenuity and evolution will expand the scope of protein function well beyond Mother Nature's designs.

Item Type:Article
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URLURL TypeDescription CentralArticle
Brustad, Eric M.0000-0002-7031-5433
Arnold, Frances H.0000-0002-4027-364X
Additional Information:© 2011 Elsevier. Available online 23 December 2010. The authors thank Mary Farrow, Christopher Snow, Philip Romero, and Crystal Dilworth for thoughtful discussions during the preparation of this manuscript. EB is supported by a Ruth M Kirschstein NIH postdoctoral fellowship Award Number F32GM087102 from the National Institute of General Medical Sciences. We also acknowledge support from the Jacobs Institute for Molecular Engineering for Medicine and NIH 1-R01-DA028299-01.
Funding AgencyGrant Number
NIH Postdoctoral FellowshipF32GM087102
Jacobs Institute for Molecular Engineering and MedicineUNSPECIFIED
National Institute of General Medical SciencesUNSPECIFIED
Issue or Number:2
PubMed Central ID:PMC3080047
Record Number:CaltechAUTHORS:20110518-102635009
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Official Citation:Eric M Brustad, Frances H Arnold, Optimizing non-natural protein function with directed evolution, Current Opinion in Chemical Biology, Volume 15, Issue 2, Biocatalysis and Biotransformation/Bioinorganic Chemistry, April 2011, Pages 201-210, ISSN 1367-5931, DOI: 10.1016/j.cbpa.2010.11.020. (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:23710
Deposited By: Ruth Sustaita
Deposited On:18 May 2011 18:12
Last Modified:09 Nov 2021 16:17

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