A Caltech Library Service

P450_(BM3)-Axial Mutations: A Gateway to Non-Natural Reactivity

Hyster, Todd K. and Arnold, Frances H. (2015) P450_(BM3)-Axial Mutations: A Gateway to Non-Natural Reactivity. Israel Journal of Chemistry, 55 (1). pp. 14-20. ISSN 0021-2148. doi:10.1002/ijch.201400080.

Full text is not posted in this repository. Consult Related URLs below.

Use this Persistent URL to link to this item:


Enzymes capable of catalyzing non-natural reactions have the potential to alter the way relevant molecules are prepared on-scale. Efforts to this end have largely focused on combining non-natural cofactors with proteins lacking catalytic function to obtain non-natural reactivity. An alternative approach is to utilize a native cofactor to catalyze non-natural reactions. Recently, our group demonstrated that heme-containing cytochrome P450s are able to catalyze the highly selective cyclopropanation of alkenes. Superior activity was observed upon changing the axial cysteine to serine (“P411”). Mutation at the conserved axial ligand has enabled P450s to catalyze other non-natural reactions such as N—H insertion and C—H amination.

Item Type:Article
Related URLs:
URLURL TypeDescription
Hyster, Todd K.0000-0003-3560-355X
Arnold, Frances H.0000-0002-4027-364X
Additional Information:© 2014 Wiley-VCH Verlag GmbH & Co. Received: May 1, 2014. Accepted: May 27, 2014. Article first published online: 20 Aug 2014. We have described the work of many former and current Arnold Lab students and postdoctoral fellows, including Pedro Coelho, Eric Brustad, John McIntosh, Jane Z. Wang, Chris Farwell, Hans Renata, Todd Hyster, and Nicole Peck. The authors also gratefully acknowledge support from the Jacobs Institute for Molecular Engineering for Medicine, at Caltech, and the Department of the Navy, Office of Naval Research (grant N00014-11-1-0205). T. K. H. is supported by a Ruth L. Kirschstein NRSA postdoctoral fellowship (1F32GM108143). The content of this paper is solely the responsibility of the authors and does not represent the official views of the funding agencies. We also thank John McIntosh and Sheel Dodani for helpful comments on this manuscript. Early View (Online Version of Record published before inclusion in an issue).
Funding AgencyGrant Number
Jacobs Institute for Molecular Engineering for MedicineUNSPECIFIED
Office of Naval Research (ONR)N00014-11-1-0205
NIH Predoctoral Fellowship1F32GM108143
NIH Predoctoral FellowshipCA138126
Subject Keywords:amination; axial ligation; cyclopropanes; enzyme catalysis; P450
Issue or Number:1
Record Number:CaltechAUTHORS:20140825-135432162
Persistent URL:
Official Citation:Hyster, T. K. and Arnold, F. H. (2015), P450BM3-Axial Mutations: A Gateway to Non-Natural Reactivity. Isr. J. Chem., 55: 14–20. doi: 10.1002/ijch.201400080
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:48857
Deposited By: Ruth Sustaita
Deposited On:25 Aug 2014 21:19
Last Modified:10 Nov 2021 18:36

Repository Staff Only: item control page