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Expanding P450 catalytic reaction space through evolution and engineering

McIntosh, John A. and Farwell, Christopher C. and Arnold, Frances H. (2014) Expanding P450 catalytic reaction space through evolution and engineering. Current Opinion in Chemical Biology, 19 . pp. 126-134. ISSN 1367-5931. PMCID PMC4008644. http://resolver.caltech.edu/CaltechAUTHORS:20140407-153730279

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Abstract

Advances in protein and metabolic engineering have led to wider use of enzymes to synthesize important molecules. However, many desirable transformations are not catalyzed by any known enzyme, driving interest in understanding how new enzymes can be created. The cytochrome P450 enzyme family, whose members participate in xenobiotic metabolism and natural products biosynthesis, catalyzes an impressive range of difficult chemical reactions that continues to grow as new enzymes are characterized. Recent work has revealed that P450-derived enzymes can also catalyze useful reactions previously accessible only to synthetic chemistry. The evolution and engineering of these enzymes provides an excellent case study for how to genetically encode new chemistry and expand biology's reaction space.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.cbpa.2014.02.001DOIArticle
http://www.sciencedirect.com/science/article/pii/S1367593114000155PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008644PubMed CentralArticle
ORCID:
AuthorORCID
Arnold, Frances H.0000-0002-4027-364X
Additional Information:© 2014 Elsevier Ltd. The authors acknowledge the support of the Jacobs Institute of Molecular Medicine at Caltech and the Office of Naval Research (grant N00014-11-1-0205). JAM is supported by an NIH Ruth L. Kirschstein National Research Service Award (F32GM101792) and CCF is supported by an NSF Graduate Research Fellowship. The content is solely the responsibility of the authors and does not represent the official views of any of the funding agencies. We thank Devin Trudeau, Jackson Cahn, Jane Wang, Ryan Lauchli, Sabine Brinkmann-Chen, Sheel Dodani, Tillman Heinisch, Todd Hyster, and Martin Enqvist for helpful comments on several versions of this review. The authors are aware of no conflicts of interest regarding the preparation and submission of this manuscript.
Funders:
Funding AgencyGrant Number
Jacobs Institute for Molecular Engineering for MedicineUNSPECIFIED
Office of Naval Research (ONR)N00014-11-1-0205
NIH Predoctoral FellowshipF32GM101792
NSF Graduate Research FellowshipUNSPECIFIED
PubMed Central ID:PMC4008644
Record Number:CaltechAUTHORS:20140407-153730279
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20140407-153730279
Official Citation:John A McIntosh, Christopher C Farwell, Frances H Arnold, Expanding P450 catalytic reaction space through evolution and engineering, Current Opinion in Chemical Biology, Volume 19, April 2014, Pages 126-134, ISSN 1367-5931, http://dx.doi.org/10.1016/j.cbpa.2014.02.001. (http://www.sciencedirect.com/science/article/pii/S1367593114000155)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:44719
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:08 Apr 2014 14:20
Last Modified:08 Sep 2017 23:08

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