title: Engineering a dirhodium artificial metalloenzyme for selective olefin cyclopropanation.
abstract: Artificial metalloenzymes (ArMs) formed by incorporating synthetic metal catalysts into protein scaffolds have the potential to impart to chemical reactions selectivity that would be difficult to achieve using metal catalysts alone. In this work, we covalently link an alkyne-substituted dirhodium catalyst to a prolyl oligopeptidase containing a genetically encoded L-4-azidophenylalanine residue to create an ArM that catalyses olefin cyclopropanation. Scaffold mutagenesis is then used to improve the enantioselectivity of this reaction, and cyclopropanation of a range of styrenes and donor-acceptor carbene precursors were accepted. The ArM reduces the formation of byproducts, including those resulting from the reaction of dirhodium-carbene intermediates with water. This shows that an ArM can improve the substrate specificity of a catalyst and, for the first time, the water tolerance of a metal-catalysed reaction. Given the diversity of reactions catalysed by dirhodium complexes, we anticipate that dirhodium ArMs will provide many unique opportunities for selective catalysis.
authors.affiliation: Coskata Inc. 4575 Weaver Parkway, Warrenville, IL 60555, USA.
authors.forename: Poonam
authors.initials: P
authors.lastname: Srivastava
authors.affiliation: Department of Chemistry, University of Chicago 5735 S. Ellis Avenue, Chicago, IL 60637, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Chemistry, University of Chicago 5735 S. Ellis Avenue, Chicago, IL 60637, USA.
authors.forename: Ken
authors.initials: K
authors.lastname: Ellis-Guardiola
authors.affiliation: Department of Chemistry, University of Chicago 5735 S. Ellis Avenue, Chicago, IL 60637, USA.
authors.forename: Jared C
authors.initials: JC
authors.lastname: Lewis
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D002384:Catalysis; D003521:Cyclopropanes / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D000085822:Prolyl Oligopeptidases; D012238:Rhodium / Q000737:chemistry*; D012697:Serine Endopeptidases / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; D003521:Cyclopropanes; D009942:Organometallic Compounds; C030797:cyclopropane; D012238:Rhodium; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases