Enzyme-Catalyzed Halogenation and Oxidation

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The focus of this project is the reactivity of vanadium bromoperoxidase isolated from marine organisms (e.g., Ascophyllum nodosum, Fucus distichus Macrocystis pyrifera). The marine environment is a very rich source of halogenated and selectively oxidized metabolites, many of which have important biological activities (e.g., chemical defense,, antimicrobial), and applications as pharmaceuticals (antineoplastic, antiinflammatory, antifungal, antibacterial) and specialty chemicals (e.g., dyes). V-BrPO catalyzes the bromination of certain organic compounds and the oxidation of others. The PI has shown that in the absence of a good substrate for bromination, V-BrPO catalyzes the formation of singlet oxygen. V-BrPO is not inactivated by high concentrations of singlet oxygen or oxidized bromine species, contrary to the behavior of the FeHeme haloperoxidases. The plan is to investigate the selectivity of bromination vs oxidation for important marine natural product precursors (e.g., indoles, furans, B-diketons and B-ketoacids), the kinetics and mechanism of bromination and oxidation. The mechanism of chloroperoxidase activity of the vanadium enzyme which the PI has recently discovered , will also be investigated. The non heme chloroperoxidase from the fungus Curvularia inaequalis will be studied, including determination of the active-site metal ion (e.g., likely to be iron, zinc or vanadium), the kinetics and mechanism of halogenation vs dioxygen formation, and the relative reactivity of oxidation vs halogenation.