Decarboxylation of Fatty Acids to Terminal Alkenes by Cytochrome P450 Compound I Job L. Grant Chun H. Hsieh Thomas M. Makris 10.1021/jacs.5b01965.s001 https://acs.figshare.com/articles/journal_contribution/Decarboxylation_of_Fatty_Acids_to_Terminal_Alkenes_by_Cytochrome_P450_Compound_I/2174251 OleT<sub>JE</sub>, a cytochrome P450, catalyzes the conversion of fatty acids to terminal alkenes using hydrogen peroxide as a cosubstrate. Analytical studies with an eicosanoic acid substrate show that the enzyme predominantly generates nonadecene and that carbon dioxide is the one carbon coproduct of the reaction. The addition of hydrogen peroxide to a deuterated substrate–enzyme (E–S) complex results in the transient formation of an iron­(IV) oxo π cation radical (Compound I) intermediate which is spectroscopically indistinguishable from those that perform oxygen insertion chemistries. A kinetic isotope effect for Compound I decay suggests that it abstracts a substrate hydrogen atom to initiate fatty acid decarboxylation. Together, these results indicate that the initial mechanism for alkene formation, which does not result from oxygen rebound, is similar to that widely suggested for P450 monooxygenation reactions. 2015-04-22 00:00:00 hydrogen peroxide P 450 monooxygenation reactions oxygen insertion chemistries alkene substrate hydrogen atom Compound formation eicosanoic acid substrate show Cytochrome P 450