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Enantioselective, intermolecular benzylic C–H amination catalysed by an engineered iron-haem enzyme

Prier, Christopher K. and Zhang, Ruijie K. and Buller, Andrew R. and Brinkmann-Chen, Sabine and Arnold, Frances H. (2017) Enantioselective, intermolecular benzylic C–H amination catalysed by an engineered iron-haem enzyme. Nature Chemistry, 9 (7). pp. 629-634. ISSN 1755-4330. PMCID PMC5555633. doi:10.1038/nchem.2783.

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C–H bonds are ubiquitous structural units of organic molecules. Although these bonds are generally considered to be chemically inert, the recent emergence of methods for C–H functionalization promises to transform the way synthetic chemistry is performed. The intermolecular amination of C–H bonds represents a particularly desirable and challenging transformation for which no efficient, highly selective, and renewable catalysts exist. Here we report the directed evolution of an iron-containing enzymatic catalyst—based on a cytochrome P450 monooxygenase—for the highly enantioselective intermolecular amination of benzylic C–H bonds. The biocatalyst is capable of up to 1,300 turnovers, exhibits excellent enantioselectivities, and provides access to valuable benzylic amines. Iron complexes are generally poor catalysts for C–H amination: in this catalyst, the enzyme's protein framework confers activity on an otherwise unreactive iron-haem cofactor.

Item Type:Article
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URLURL TypeDescription ReadCube access CentralArticle
Prier, Christopher K.0000-0003-0902-1636
Zhang, Ruijie K.0000-0002-7251-5527
Buller, Andrew R.0000-0002-9635-4844
Brinkmann-Chen, Sabine0000-0002-5419-4192
Arnold, Frances H.0000-0002-4027-364X
Alternate Title:Enantioselective, Intermolecular Benzylic C–H Amination Catalyzed by an Engineered Iron-Heme Enzyme
Additional Information:© 2017 Macmillan Publishers Limited. Received 14 March 2017. Accepted 21 April 2017. Published online 29 May 2017. Our research is supported by the National Science Foundation, Division of Molecular and Cellular Biosciences (grant MCB-1513007) and by funds from the American Recovery and Reinvestment Act (ARRA) through the National Institutes of Health Shared Instrumentation Grant Program (S10RR027203). C.K.P. thanks the Resnick Sustainability Institute for a postdoctoral fellowship. R.K.Z. was supported by a National Science Foundation Graduate Research Fellowship (NSF GRFP; DGE-1144469), is a trainee in the Caltech Biotechnology Leadership Program, and has received financial support from the Donna and Benjamin M. Rosen Bioengineering Center. A.R.B. is funded by a Ruth Kirschstein NIH Postdoctoral Fellowship F32G110851. We thank S. Virgil, J. Kaiser, and R. D. Lewis for experimental assistance, and O. F. Brandenberg, S. C. Hammer, and S. B. J. Kan for helpful discussion and comments on the manuscript. These authors contributed equally to this work. Christopher K. Prier & Ruijie K. Zhang. Author ontributions: C.K.P. and R.K.Z. designed, carried out, and analysed all amination experiments, with F.H.A. providing guidance. C.K.P., R.K.Z. and S.B.-C. obtained protein crystals. R.K.Z. and A.R.B. solved the crystal structure. C.K.P. and F.H.A. wrote the manuscript with input from all of the authors. Data availability: Complete experimental procedures, including synthesis methods for all compounds, characterization data, and details of bioconversion experiments are described in the Supplementary Information. The crystal structure of P411_(BM3) P-4 A82L A78V F263L has been deposited in the Protein Data Bank (PDB) under accession code 5UCW. The authors declare no competing financial interests.
Group:Resnick Sustainability Institute, Rosen Bioengineering Center
Funding AgencyGrant Number
American Recovery and Reinvestment Act (ARRA)UNSPECIFIED
Resnick Sustainability InstituteUNSPECIFIED
NSF Graduate Research FellowshipDGE-1144469
Donna and Benjamin M. Rosen Bioengineering CenterUNSPECIFIED
NIH Postdoctoral FellowshipF32G110851
Issue or Number:7
PubMed Central ID:PMC5555633
Record Number:CaltechAUTHORS:20170413-120718900
Persistent URL:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:76551
Deposited By: George Porter
Deposited On:30 May 2017 17:57
Last Modified:25 Mar 2022 23:17

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