Enzyme-Catalyzed Halogenation and Oxidation

本项目的重点是从海洋生物(如节瘤蘑菇、巨孢子藻)中分离出的钒溴过氧化物酶的反应性。海洋环境是卤化和选择性氧化代谢物的非常丰富的来源，其中许多具有重要的生物活性(例如，化学防御、抗菌剂)，以及作为药物(抗肿瘤、抗炎、抗真菌、抗菌)和特殊化学品(例如，染料)的应用。V-BrPO催化某些有机化合物的溴化和其他有机化合物的氧化。等电点表明，在没有良好的溴化底物的情况下，V-BrPO催化形成单线态氧。V-BrPO不会被高浓度的单线态氧或氧化的溴物种灭活，这与Feheme卤代过氧化物酶的行为相反。该计划将研究重要的海洋天然产物前体(如吲哚、呋喃、B-二酮和B-酮酸)的溴化和氧化的选择性，溴化和氧化的动力学和机理。还将对PI最近发现的钒酶的氯过氧化物酶活性的机理进行研究。将研究来自真菌Curveraria inaequis的非血红素氯过氧化物酶，包括活性中心金属离子(例如，可能是铁、锌或钒)的测定，卤化与氧气形成的动力学和机理，以及氧化与卤化的相对反应性。

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.