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

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.

SUBMITTER: Hyster TK

PROVIDER: S-EPMC4227740 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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

Hyster Todd K TK Farwell Christopher C CC Buller Andrew R AR McIntosh John A JA Arnold Frances H FH

Journal of the American Chemical Society 20141024 44

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 identica ...[more]

PMID: 25325618

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