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Catalysts on Demand: Selective Oxidations by Laboratory-Evolved Cytochrome P450 BM3

Lewis, Jared C. and Arnold, Frances H. (2009) Catalysts on Demand: Selective Oxidations by Laboratory-Evolved Cytochrome P450 BM3. Chimia, 63 (6). pp. 309-312. ISSN 0009-4293. doi:10.2533/chimia.2009.309.

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Efficient catalysts for selective oxidation of C-H bonds using atmospheric oxygen are highly desirable to decrease the economic and environmental costs associated with conventional oxidation processes. We have used methods of directed evolution to generate variants of bacterial cytochrome P450 BM3 that catalyze hydroxylation and epoxidation of a wide range of nonnative substrates. This fatty acid hydroxylase was converted to a propane monooxygenase (PMO) capable of hydroxylating propane at rates comparable to that of BM3 on its natural substrates. Variants along the PMO evolutionary lineage showed broadened substrate scope; these became the starting points for evolution of a wide array of enzymes that can hydroxylate and derivatize organic scaffolds. This work demonstrates how a single member of enzyme family is readily converted by evolution into a whole family of catalysts for organic synthesis.

Item Type:Article
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Arnold, Frances H.0000-0002-4027-364X
Additional Information:© 2009 Schweizerische Chemische Gesellschaft. Received: January 28, 2009. This work was supported by the U.S. Department of Agriculture, grant 2006-35505-16660, and by the U.S. Department of Energy, grant DE-FG02-06ER15762, to F.H.A. J.C.L is supported by the U.S. National Institutes of Health, fellowship 1F32GM079932-01.
Funding AgencyGrant Number
Department of Agriculture (USDA)2006-35505-16660
Department of Energy (DOE)DE-FG02-06ER15762
NIH Predoctoral Fellowship1F32GM079932-01
Subject Keywords:Biocatalysis; Evolution; Drug metabolite; Oxidation; P450
Issue or Number:6
Record Number:CaltechAUTHORS:20090914-094240617
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:15831
Deposited By: George Porter
Deposited On:02 Oct 2009 19:02
Last Modified:08 Nov 2021 23:22

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