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Combinatorial Alanine Substitution Enables Rapid Optimization of Cytochrome P450_(BM3) for Selective Hydroxylation of Large Substrates

Lewis, Jared C. and Mantovani, Simone M. and Fu, Yu and Snow, Christopher D. and Komor, Russell S. and Wong, Chi-Huey and Arnold, Frances H. (2010) Combinatorial Alanine Substitution Enables Rapid Optimization of Cytochrome P450_(BM3) for Selective Hydroxylation of Large Substrates. ChemBioChem, 11 (18). pp. 2502-2505. ISSN 1439-4227. PMCID PMC4447097. http://resolver.caltech.edu/CaltechAUTHORS:20110118-104553247

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Abstract

Made for each other: Combinatorial alanine substitution of active site residues in a thermostable cytochrome P450_(BM3) variant was used to generate an enzyme that is active with large substrates. Selective hydroxylation of methoxymethylated monosaccharides, alkaloids, and steroids was thus made possible (see Scheme). This approach could be useful for improving the activity of enzymes that show only limited activity with larger substrates.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1002/cbic.201000565 DOIArticle
http://onlinelibrary.wiley.com/doi/10.1002/cbic.201000565/abstractPublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447097PubMed CentralArticle
ORCID:
AuthorORCID
Arnold, Frances H.0000-0002-4027-364X
Additional Information:© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Received: September 21, 2010. Published online on November 24, 2010. J.C.L. is supported by a U.S. National Institutes of Health Pathways to Independence Award (1K99M087551-01A1). S.M.M. is supported by the Fundacao Coordenadoria de Aperfeicoamento de Pessoal de Nivel Superior (CAPES; 1756-09-5). This work was supported by the U.S. National Institutes of Health (2R01 M068664-05A1), the U.S. Department of Energy, Office of Basic Science, grant DE-FG02-06ER15762, and King Abdullah University of Science and Technology (KAUST), Award No. KUS-F1-028-03.
Funders:
Funding AgencyGrant Number
NIH1K99M087551-01A1
NIH2R01 M068664-05A1
Fundacao Coordenadoria de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)1756-09-5
Department of Energy (DOE)DE-FG02-06ER15762
King Abdullah University of Science and Technology (KAUST)KUS-F1-028-03
Subject Keywords:alkaloids; biocatalysis; cytochromes; monosaccharides; steroids
PubMed Central ID:PMC4447097
Record Number:CaltechAUTHORS:20110118-104553247
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20110118-104553247
Official Citation:Lewis, J. C., Mantovani, S. M., Fu, Y., Snow, C. D., Komor, R. S., Wong , C.-H. and Arnold, F. H. (2010), Combinatorial Alanine Substitution Enables Rapid Optimization of Cytochrome P450BM3 for Selective Hydroxylation of Large Substrates. ChemBioChem, 11: 2502–2505. doi: 10.1002/cbic.201000565
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:21785
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:31 Jan 2011 23:44
Last Modified:24 Jul 2017 17:41

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