Event Information
Mechanistic Studies of Oxidative Halophenol Dehalogenation by Heme-Containing Peroxidases
- Abstract:
Toxic halophenols are produced through industrial processes and pose both environmental risks and health hazards. Curiously, marine worms in coastal sediments also produce noxious halophenols, apparently to deter predators. To survive in the presence of such poisons, the marine worm Amphitrite ornata uses a catalytically-active globin dehaloperoxidase to oxidatively dehalogenate halophenols to the corresponding quinones. Two mechanisms for this reaction have been proposed: a direct two-electron oxygen atom transfer and a mechanism involving two successive one-electron steps via a phenoxy radical. We have also shown that the most versatile heme-containing peroxidase, Caldariomyces fumago chloroperoxidase (CCPO) - best known as a halogenation catalyst - and the oxygen transport protein myoglobin both catalyze halophenol dehalogenation. With all three enzymes, the mechanism has been probed using para-halophenols, and the product distribution is consistent with involvement of a phenoxy radical intermediate. Furthermore, since CCPO forms relatively stable high-valent Compound I and II intermediates (respectively two and one electron oxidized relative to the ferric state), it provides an ideal system with which to use rapid-scan stopped-flow techniques to differentiate between the two mechanisms. Parallel studies with A. ornata dehaloperoxidase and myoglobin have also been pursued. Finally, as it has recently shown that phenoxy radicals and quinones bind irreversibly and covalently to DNA, the ability of myoglobin to oxidatively dehalogenate halophenols may explain their carcinogenicity.
Host: A.L. Crumbliss
Departmental Seminar