J. Martin Bollinger
Thu, Mar. 24, 2016, 4:30pm
Frick Chemistry Laboratory, Taylor Auditorium
Host: Mohammad Seyedsayamdost
Demystifying the chemical magic of non-heme-iron enzymes in natural product biosynthesis
Non-heme-iron (NH-Fe) enzymes activate O2 for an array of biomedically and agriculturally important oxidation reactions. Our past decade’s work has characterized iron(IV)-oxo (ferryl) complexes in several such NH-Fe enzymes.1 Most often, the ferryl complexes generate substrate radicals by abstracting hydrogen (H•) from aliphatic carbons,2-6 leading to formation of new C–O,2-4 C–Cl/Br,5 or C–S bonds.1 Motivated by our success in rationalizing the divergent outcomes of the NH-Fe 2-(oxo)glutarate-dependent aliphatic hydroxylases and halogenases,6 we now seek both to exploit the ferryl manifold for novel carbon-functionalization reactions7 and to explain the structural and mechanistic bases for several other natural reaction types, including dehydrogenation of an alcohol to epoxide,8 stereo-inversion of a chiral carbon,9 and desaturation and cleavage of C–C bonds, that are initiated by ferryl complexes in other NH-Fe enzymes. Insight obtained will inform combinatorial design of new antibiotic and anticancer drugs.