Enzyme-Catalyzed Halogenation and Oxidation

酶催化卤化和氧化

基本信息

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

项目摘要

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.

该项目的重点是从海洋生物（例如泡叶藻、墨角藻、巨囊藻）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）以及药物（抗肿瘤、抗炎、抗真菌、抗菌）和特种化学品（例如化学合成）的应用。、染料）。 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。 PI 表明，在缺乏良好的溴化底物的情况下，V-BrPO 会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物质灭活，这与 FeHeme 卤过氧化物酶的行为相反。该计划旨在研究重要海洋天然产物前体（例如吲哚、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。 PI最近发现的钒酶的氯过氧化物酶活性机制也将被研究。将研究来自真菌 Curvularia inaequalis 的非血红素氯过氧化物酶，包括活性位点金属离子（例如，可能是铁、锌或钒）的测定、卤化与双氧形成的动力学和机制，以及氧化与卤化。