title: Directed evolution of cytochrome c for carbon-silicon bond formation: Bringing silicon to life.
abstract: Enzymes that catalyze carbon-silicon bond formation are unknown in nature, despite the natural abundance of both elements. Such enzymes would expand the catalytic repertoire of biology, enabling living systems to access chemical space previously only open to synthetic chemistry. We have discovered that heme proteins catalyze the formation of organosilicon compounds under physiological conditions via carbene insertion into silicon-hydrogen bonds. The reaction proceeds both in vitro and in vivo, accommodating a broad range of substrates with high chemo- and enantioselectivity. Using directed evolution, we enhanced the catalytic function of cytochrome c from Rhodothermus marinus to achieve more than 15-fold higher turnover than state-of-the-art synthetic catalysts. This carbon-silicon bond-forming biocatalyst offers an environmentally friendly and highly efficient route to producing enantiopure organosilicon molecules.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: S B Jennifer
authors.initials: SB
authors.lastname: Kan
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Russell D
authors.initials: RD
authors.lastname: Lewis
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA. frances@cheme.caltech.edu.
authors.forename: Frances H
authors.initials: FH
authors.lastname: Arnold
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D055162:Biocatalysis; D002244:Carbon / Q000737:chemistry*; D045304:Cytochromes c / Q000737:chemistry* / Q000235:genetics; D019020:Directed Molecular Evolution / Q000379:methods*; D006860:Hydrogen Bonding; D008697:Methane / Q000031:analogs & derivatives / Q000737:chemistry; D017646:Organosilicon Compounds / Q000138:chemical synthesis*; D045245:Rhodothermus / Q000201:enzymology*; D012825:Silicon / Q000737:chemistry*; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D017646:Organosilicon Compounds; C030011:carbene; D002244:Carbon; D045304:Cytochromes c; D008697:Methane; D012825:Silicon