Mechanistic and Structural Studies of Novel Heme-Containing Peroxidases

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9604004 Dawson Heme-containing peroxidases catalyze organic substrate oxidation with concomitant reduction of hydrogen peroxide to water. Two novel heme-containing peroxidases, one able to incorporate halogens into aromatic substrates and the other able to remove them, have recently been isolated from marine organisms and initially characterized. The properties of these enzymes challenge the current dogma of how peroxidases function: one chlorinates substrates without having a thiolate proximal ligand and the other both oxygenates and dehalogenates haloaromatics including the defluorination of fluoroaromatics. To better understand the unusual properties of these two heme peroxidases, spectroscopic, structural and mechanistic investigations will be carried out. These studies will involve the use of magnetic circular dichroism, EPR, and resonance Raman spectroscopy as well as high resolution crystallography to fully characterize the metal coordination structure and complete three dimensional structures of these two enzymes. Their mechanisms of action will be extensively examined including the use of isotopically labelled hydrogen peroxide to compare and contrast their mechanisms of hydrogen peroxide activation with those of the well studied plant peroxidases. Two novel enzymes from marine sources which are capable of generating and/or handling halogen-containing aromatic compounds have been isolated and will be thoroughly investigated including the determination of their mechanism of action and three dimensional structure. The first enzyme is able to incorporate halogens into aromatic substrates and may find applications as an industrial biocatalyst in the synthesis of halogen-containing aromatics. The second enzyme is able to remove halogens from aromatic compounds and is likely to have applications in bioremediation of water or soil contaminated with haloaromatics.