TOPIC：Exploring the reactivity of heme-thiolate oxygenases and peroxygenases – P450 vs APO
SPEAKER：John T. Groves 教授 美国科学院院士，普林斯顿大学化学系
TIME：October 12 (Wednesday) PM15:00 
LOCATION：药学院5号楼316室
INVITER：周虎臣教授(药学院)，任奇志副教授(beat365)
 

Exploring the reactivity of heme-thiolate oxygenases and peroxygenases – P450 vs APO

John T. Groves

Hugh Stott Taylor Chair of Chemistry

Department of Chemistry, Princeton University, Princeton, NJ 08544 USA

jtg(r1)Known heme-thiolate proteins include cytochrome P450, nitric oxide synthase and chloroperoxidase. Recently, a new family of fungal heme-thiolate peroxygenases have been discovered. These proteins are novel and highly efficient biocatalysts that are capable of catalyzing the oxygenation of a variety of substrates using H2O2 as the oxidant. Drug molecules are readily transformed into typical P450-type metabolites. We have found that the peroxygenases APO secreted by the agaric fungi

Agrocybe aegerita and Marasmius rotula catalyze the H2O2-dependent hydroxylation of simple alkanes and other organic substrates with high efficiency. Iron(IV) intermediates, compound I and compound II, of APO have been spectroscopically observed and kinetically characterized. The pKa of compound II [Cys-S Fe(IV)-OH] has been determined by a novel reductive technique. The reduction potential and the O-H bond dissociation energy of Fe(IV)-OH have also been determined, thus accessing the reduction potential of compound I as well. APO-II is shown to have surprisingly high reactivity toward C-H and phenolic O-H hydrogen atom abstraction. The mechanism of C-H hydroxylation by APO will be compared and contrasted to those of other heme proteins and model porphyrin systems. Supported by the US National Institutes of Health (2R37 GM036298-30).

References
1. Xiaoshi Wang, René Ullrich, Martin Hofrichter, and John T. Groves, Proc. Nat. Acad. Sci. U.S.A., 2015, 112, 3686-3691.
2. John T. Groves and Nicholas C. Boaz, Science, 2014, 345, 142-143.
3. John T. Groves, Nature Chemistry, 2014, 6, 89-91.
4. Nicholas C. Boaz, Seth R. Bell, and John T. Groves, J. Am. Chem. Soc. 2015, 137 (8), 2875–2885.
5.Xiaoshi Wang, Sebastian Peter, Matthias Kinne, Martin Hofrichter, John T. Groves J. Am. Chem. Soc., 2012, 134, 12897–12900.
6.Xiaoshi Wang, Sebastian Peter, René Ullrich, Martin Hofrichter, and John T. Groves, Angew. Chem. Int. Ed. 2013, 52, 9238-9241.