These authors contributed equally to this work.
Enantioselective Intramolecular CH Amination Catalyzed by Engineered Cytochrome P450 Enzymes In Vitro and In Vivo†
Article first published online: 24 JUL 2013
Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Angewandte Chemie International Edition
Volume 52, Issue 35, pages 9309–9312, August 26, 2013
How to Cite
McIntosh, J. A., Coelho, P. S., Farwell, C. C., Wang, Z. J., Lewis, J. C., Brown, T. R. and Arnold, F. H. (2013), Enantioselective Intramolecular CH Amination Catalyzed by Engineered Cytochrome P450 Enzymes In Vitro and In Vivo . Angew. Chem. Int. Ed., 52: 9309–9312. doi: 10.1002/anie.201304401
We thank S. Virgil and the 3CS catalysis center at Caltech for assistance with HPLC and LC–MS analyses, and D. Montgomery, Y. Liu, N. Peck, K. Rabe, R. Lauchli, and D. VanderVelde for helpful discussions. This work was supported by the Department of the Navy, Office of Naval Research (grant N00014-11-1-0205), and by the Jacobs Institute for Molecular Engineering for Medicine at Caltech. J.A.M. and Z.J.W. are supported by Ruth L. Kirschstein National Research Service Awards (F32GM101792) and (F32EB015846). C.C.F. is supported by an NSF Graduate Research Fellowship.
- Issue published online: 22 AUG 2013
- Article first published online: 24 JUL 2013
- Manuscript Revised: 12 JUN 2013
- Manuscript Received: 22 MAY 2013
- Department of the Navy
- Office of Naval Research. Grant Number: N00014-11-1-0205
- Jacobs Institute for Molecular Engineering for Medicine at Caltech
- Ruth L. Kirschstein National Research Service Awards. Grant Numbers: F32GM101792, F32EB015846
- CH activation;
- enzyme catalysis;
- protein engineering;
- synthetic biology
Nitrogen activation: Though P450 enzymes are masters of oxygen activation and insertion into CH bonds, their ability to use nitrogen for the same purpose has so far not been explored. Engineered variants of cytochrome P450BM3 have now been found to catalyze intramolecular CH aminations in azide substrates. Mutations to two highly conserved residues significantly increased this activity.