title: Catalytic strategy for carbon-carbon bond scission by the cytochrome P450 OleT.
abstract: OleT is a cytochrome P450 that catalyzes the hydrogen peroxide-dependent metabolism of Cn chain-length fatty acids to synthesize Cn-1 1-alkenes. The decarboxylation reaction provides a route for the production of drop-in hydrocarbon fuels from a renewable and abundant natural resource. This transformation is highly unusual for a P450, which typically uses an Fe(4+)-oxo intermediate known as compound I for the insertion of oxygen into organic substrates. OleT, previously shown to form compound I, catalyzes a different reaction. A large substrate kinetic isotope effect (≥8) for OleT compound I decay confirms that, like monooxygenation, alkene formation is initiated by substrate C-H bond abstraction. Rather than finalizing the reaction through rapid oxygen rebound, alkene synthesis proceeds through the formation of a reaction cycle intermediate with kinetics, optical properties, and reactivity indicative of an Fe(4+)-OH species, compound II. The direct observation of this intermediate, normally fleeting in hydroxylases, provides a rationale for the carbon-carbon scission reaction catalyzed by OleT.
authors.affiliation: Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC 29208.
authors.forename: Job L
authors.initials: JL
authors.lastname: Grant
authors.affiliation: Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC 29208.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Mitchell
authors.affiliation: Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC 29208 makrist@mailbox.sc.edu.
authors.forename: Thomas Michael
authors.initials: TM
authors.lastname: Makris
mesh_terms: D000475:Alkenes / Q000737:chemistry* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D055162:Biocatalysis; D002244:Carbon / Q000737:chemistry / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008956:Models, Chemical; D010084:Oxidation-Reduction; D040141:Staphylococcaceae / Q000737:chemistry* / Q000201:enzymology
chemical_list: D000475:Alkenes; D001426:Bacterial Proteins; D005227:Fatty Acids; D002244:Carbon; D003577:Cytochrome P-450 Enzyme System
keywords: compound II; cytochrome P450; hydrocarbon; metal−oxo; oxygen activation