Catalytic strategy for carbon–carbon bond scission by the cytochrome P450 OleT

• Published in: Proceedings of the National Academy of Sciences - PNAS 2016-09, Vol.113 (36), p.10049-10054
• Main Authors: Grant, Job L., Mitchell, Megan E., Makris, Thomas Michael
• Format: Article
• Language: English
• Subjects: Alkenes; Alkenes - chemistry; Alkenes - metabolism; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Biocatalysis; Biological Sciences; Carbon; Carbon - chemistry; Carbon - metabolism; Catalysis; Cytochrome; Cytochrome P-450 Enzyme System - chemistry; Cytochrome P-450 Enzyme System - metabolism; Fatty Acids - chemistry; Fatty Acids - metabolism; Hydrogen peroxide; Kinetics; Metabolism; Models, Chemical; Natural resources; Optical properties; Oxidation-Reduction; Physical Sciences; Staphylococcaceae - chemistry; Staphylococcaceae - enzymology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1606294113

OleT is a cytochrome P450 that catalyzes the hydrogen peroxide-dependent metabolism of C n chain-length fatty acids to synthesize C n-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 Fe4+−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 Fe4+−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.