Olefin Cyclopropanation via Carbene Transfer Catalyzed by Engineered Cytochrome P450 Enzymes

• Published in: Science (American Association for the Advancement of Science) Vol. 339; no. 6117; pp. 307 - 310
• Main Authors: Coelho, Pedro S., Brustad, Eric M., Kannan, Arvind, Arnold, Frances H.
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 18-01-2013; The American Association for the Advancement of Science
• Subjects: Activation; Alkenes - chemistry; Bacillus megaterium - enzymology; Carbenes; Carbon; Catalysis; Cyclopropanes - chemistry; Cytochrome P-450 Enzyme System - chemistry; Cytochrome P-450 Enzyme System - genetics; Enzymes; Genetic engineering; Hydrocarbons; Iron; Methane - analogs & derivatives; Methane - chemistry; Models, Chemical; Oxidation; Oxygen; Protein Engineering; Stereoisomerism; Tuning
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1231434

Transition metal—catalyzed transfers of carbenes, nitrenes, and oxenes are powerful methods for functionalizing C=C and C—H bonds. Nature has evolved a diverse toolbox for oxene transfers, as exemplified by the myriad monooxygenation reactions catalyzed by cytochrome P450 enzymes. The isoelectronic carbene transfer to olefins, a widely used C—C bond—forming reaction in organic synthesis, has no biological counterpart. Here we report engineered variants of cytochrome P450 BM3 that catalyze highly diastereo- and enantioselective cyclopropanation of styrenes from diazoester reagents via putative carbene transfer. This work highlights the capacity to adapt existing enzymes for the catalysis of synthetically important reactions not previously observed in nature.