Enzyme-controlled nitrogen-atom transfer enables regiodivergent C-H amination

Todd K. Hyster, Christopher C. Farwell, Andrew R. Buller, John A. McIntosh, Frances H. Arnold

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

We recently demonstrated that variants of cytochrome P450BM3 (CYP102A1) catalyze the insertion of nitrogen species into benzylic C-H bonds to form new C-N bonds. An outstanding challenge in the field of C-H amination is catalyst-controlled regioselectivity. Here, we report two engineered variants of P450BM3 that provide divergent regioselectivity for C-H amination - one favoring amination of benzylic C-H bonds and the other favoring homo-benzylic C-H bonds. The two variants provide nearly identical kinetic isotope effect values (2.8-3.0), suggesting that C-H abstraction is rate-limiting. The 2.66-Å crystal structure of the most active enzyme suggests that the engineered active site can preorganize the substrate for reactivity. We hypothesize that the enzyme controls regioselectivity through localization of a single C-H bond close to the iron nitrenoid.

Original languageEnglish (US)
Pages (from-to)15505-15508
Number of pages4
JournalJournal of the American Chemical Society
Volume136
Issue number44
DOIs
StatePublished - Nov 5 2014

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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