title: Highly diastereoselective and enantioselective olefin cyclopropanation using engineered myoglobin-based catalysts.
abstract: Using rational design, an engineered myoglobin-based catalyst capable of catalyzing the cyclopropanation of aryl-substituted olefins with catalytic proficiency (up to 46,800 turnovers) and excellent diastereo- and enantioselectivity (98-99.9%) was developed. This transformation could be carried out in the presence of up to 20 g L(-1) olefin substrate with no loss in diastereo- and/or enantioselectivity. Mutagenesis and mechanistic studies support a cyclopropanation mechanism mediated by an electrophilic, heme-bound carbene species and a model is provided to rationalize the stereopreference of the protein catalyst. This work shows that myoglobin constitutes a promising and robust scaffold for the development of biocatalysts with carbene-transfer reactivity.
authors.affiliation: Department of Chemistry, University of Rochester, 120 Trustee Road, Rochester, NY 14627 (USA).
authors.forename: Melanie
authors.initials: M
authors.lastname: Bordeaux
authors.forename: Vikas
authors.initials: V
authors.lastname: Tyagi
authors.forename: Rudi
authors.initials: R
authors.lastname: Fasan
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D002384:Catalysis; D003521:Cyclopropanes / Q000737:chemistry*; D009211:Myoglobin / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; D003521:Cyclopropanes; D009211:Myoglobin; D011994:Recombinant Proteins; C030797:cyclopropane
keywords: biocatalysis; carbenes; iron; protein engineering; small-ring systems