Diverse Engineered Heme Proteins Enable Stereodivergent Cyclopropanation of Unactivated Alkenes.

ABSTRACT: Developing catalysts that produce each stereoisomer of a desired product selectively is a longstanding synthetic challenge. Biochemists have addressed this challenge by screening nature's diversity to discover enzymes that catalyze the formation of complementary stereoisomers. We show here that the same approach can be applied to a new-to-nature enzymatic reaction, alkene cyclopropanation via carbene transfer. By screening diverse native and engineered heme proteins, we identified globins and serine-ligated "P411" variants of cytochromes P450 with promiscuous activity for cyclopropanation of unactivated alkene substrates. We then enhanced their activities and stereoselectivities by directed evolution: just 1-3 rounds of site-saturation mutagenesis and screening generated enzymes that trans

SUBMITTER: Knight AM 

PROVIDER: S-EPMC5879470 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature