Structural highlights
Publication Abstract from PubMed
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-A 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.
Enzyme-Controlled Nitrogen-Atom Transfer Enables Regiodivergent C-H Amination.,Hyster TK, Farwell CC, Buller AR, McIntosh JA, Arnold FH J Am Chem Soc. 2014 Oct 24. PMID:25325618[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hyster TK, Farwell CC, Buller AR, McIntosh JA, Arnold FH. Enzyme-Controlled Nitrogen-Atom Transfer Enables Regiodivergent C-H Amination. J Am Chem Soc. 2014 Oct 24. PMID:25325618 doi:http://dx.doi.org/10.1021/ja509308v
