Chloroperoxidase Catalytic Mechanisms

描述(申请人提供)：提出了补充计算和实验工作，以阐明烟用氯过氧化物酶(CCPO)的生物催化特性，并开发用于手性合成的改进突变体。特别是，这项工作旨在利用对接和MD计算技术确定导致高度对映专一性环氧化的CCPO活性部位的性质，并在此基础上预测、合成和检测具有更高对映专一性的突变体。其次，为了阐明长期以来存在争议的CCPO卤化机理，提出了对其进行QM和QM/MM研究。卤代反应在药物合成中具有重要意义，也可能对CCPO的环氧化反应具有重要意义。拟议研究的这两个方面都将有助于构建可能对人类健康产生重大影响的药物的合成路线。

DESCRIPTION (provided by applicant): Complementary computational and experimental work is proposed to elucidate the biocatalytic properties of C. fumago chloroperoxidase (CCPO) and develop improved mutants for chiral synthesis. In particular, the work aims to determine the properties of CCPO's active site that lead to highly enantiospecific epoxidation using docking and MD computational techniques, and on that basis, to predict, synthesize, and assay mutants with improved enantiospecificity. Secondly, a QM and QM/MM study of the halogenation mechanism of CCPO is proposed in order to elucidate the mechanism, which has long been disputed. Halogenation is important for pharmaceutical synthesis and may also have significance for CCPO's epoxidation reaction. Both aspects of the proposed research will help construct synthetic routes to drugs with possible significant impact on human health.