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Enantioselective Imidation of Sulfides via Enzyme-Catalyzed Intermolecular Nitrogen-Atom Transfer

Farwell, Christopher C. and McIntosh, John A. and Hyster, Todd K. and Wang, Z. Jane and Arnold, Frances H. (2014) Enantioselective Imidation of Sulfides via Enzyme-Catalyzed Intermolecular Nitrogen-Atom Transfer. Journal of the American Chemical Society, 136 (24). pp. 8766-8771. ISSN 0002-7863. PMCID PMC4154708. http://resolver.caltech.edu/CaltechAUTHORS:20140610-140803475

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Abstract

Engineering enzymes with novel reaction modes promises to expand the applications of biocatalysis in chemical synthesis and will enhance our understanding of how enzymes acquire new functions. The insertion of nitrogen-containing functional groups into unactivated C–H bonds is not catalyzed by known enzymes but was recently demonstrated using engineered variants of cytochrome P450_(BM3) (CYP102A1) from Bacillus megaterium. Here, we extend this novel P450-catalyzed reaction to include intermolecular insertion of nitrogen into thioethers to form sulfimides. An examination of the reactivity of different P450_(BM3) variants toward a range of substrates demonstrates that electronic properties of the substrates are important in this novel enzyme-catalyzed reaction. Moreover, amino acid substitutions have a large effect on the rate and stereoselectivity of sulfimidation, demonstrating that the protein plays a key role in determining reactivity and selectivity. These results provide a stepping stone for engineering more complex nitrogen-atom-transfer reactions in P450 enzymes and developing a more comprehensive biocatalytic repertoire.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://pubs.acs.org/doi/abs/10.1021/ja503593nPublisherArticle
http://dx.doi.org/10.1021/ja503593nDOIArticle
http://pubs.acs.org/doi/suppl/10.1021/ja503593nPublisherSupporting Information
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154708/PubMed CentralArticle
ORCID:
AuthorORCID
Arnold, Frances H.0000-0002-4027-364X
Additional Information:© 2014 American Chemical Society. ACS AuthorChoice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. Received: April 15, 2014. Publication Date (Web): May 23, 2014. Article ASAP. The authors acknowledge the support of 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). C.C.F. is supported by an NSF Graduate Research Fellowship (DGE-1144469). J.A.M., T.K.H., and Z.J.W. are supported by NIH Ruth L. Kirschstein National Research Service Awards (F32GM101792, F32GM108143, F32EB015846). We thank R. Kelly Zhang and Hans Renata for helpful comments on the manuscript, and Scott Virgil and the 3CS catalysis center for HPLC and LC-MS analysis.
Funders:
Funding AgencyGrant Number
Jacobs Institute for Molecular Engineering for MedicineUNSPECIFIED
Office of Naval Research (ONR)N00014-11-1-0205
NSF Graduate Research FellowshipDGE-1144469
NIH Predoctoral FellowshipF32GM101792
NIH Predoctoral FellowshipF32GM108143
NIH Predoctoral FellowshipF32EB015846
PubMed Central ID:PMC4154708
Record Number:CaltechAUTHORS:20140610-140803475
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20140610-140803475
Official Citation:Enantioselective Imidation of Sulfides via Enzyme-Catalyzed Intermolecular Nitrogen-Atom Transfer Christopher C. Farwell, John A. McIntosh, Todd K. Hyster, Z. Jane Wang, and Frances H. Arnold Journal of the American Chemical Society 2014 136 (24), 8766-8771
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:46185
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:10 Jun 2014 21:36
Last Modified:08 Sep 2017 23:06

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