Enzyme-Catalyzed Halogenation and Oxidation

酶催化卤化和氧化

• 批准号: 9018025
• 负责人: Alison Butler
• 金额: $ 24万
• 依托单位: University of California-Santa Barbara
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-03-01 至 1996-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9018025&HistoricalAwards=false
• 关键词: Enzyme; Catalyzed; Halogenation; Oxidation

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.

本项目的重点是从海洋生物（如：葡萄叶藻、黑角藻等）中分离的溴过氧化物钒酶的反应性。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（如化学防御、抗菌），并应用于药物（抗肿瘤、抗炎、抗真菌、抗菌）和特种化学品（如染料）。V-BrPO催化某些有机化合物的溴化和其他有机物的氧化。PI表明，在没有良好的溴化底物的情况下，V-BrPO催化单线态氧的形成。V-BrPO不会被高浓度的单线态氧或氧化溴灭活，这与铁血红素卤素过氧化物酶的行为相反。该计划旨在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）的溴化与氧化的选择性、溴化和氧化的动力学和机制。本文还将对新发现的钒酶的氯过氧化物酶活性机理进行研究。本文将对曲霉非血红素氯过氧化物酶进行研究，包括活性位点金属离子（如铁、锌或钒）的测定、卤化与双氧形成的动力学和机理、氧化与卤化的相对反应活性。