多糖单加氧酶及其模型类似物催化机制的理论研究

Polysaccharide monooxygenases (PMOs) have emerged as key enzymes utilized in biology for the degradation of biomass (such as cellulose and chitin). These enzymes utilize a mononuclear copper active center to insert an oxygen atom into biopolymers, thus opening up the polysaccharide for hydrolysis by glycoside hydrolases. It provides a useful tool for sustainable production of second-generation biofuels. However, the recent studies of PMOs focus on the gene expression and crystal structural analysis. Many questions about their reaction mechanism and structure-function relationship remain. This project will investigate the enzyme-substrate interaction, the geometry and electronic structure of the copper-oxygen species, catalytic mechanism, and reaction selectivity of PMOs by means of a variety of computational techniques (including molecular dynamics, quantum mechanical and quantum mechanical/molecular mechanical methods). Meanwhile, the reaction mechanism of the biomimetic copper complexes will be investigated by using the quantum mechanical approaches. Based on these studies, the valence bond model will be used to treat the C-H bond activation by mononuclear copper systems. The goal of this project is to understand the mechanism of mononuclear copper systems and their structure-activity realtionships, and to establish the theoretical model for describing the reaction. The results of the proposed studies will prove to be extremely valuable in designing new, more efficient copper-based catalysts.

多糖单加氧酶（PMOs）是自然界中降解常见生物质（如纤维素和甲壳素）的一类关键酶。这类酶通过单核铜中心在生物质的多糖链上添加氧基团来切断分子链，从而使多糖分子更容易被其他糖苷水解酶降解。这就为第二代生物燃料的生产提供了有利工具。然而目前对多糖单加氧酶的研究多集中在生物学的表达和结构解析上，对其催化机制，结果-功能关系都缺乏足够的了解。本项目拟采用各种计算手段（包括分子动力学、量子力学和量子力学/分子力学方法）研究多糖单加氧酶的酶-底物相互作用、含氧物种的几何结构和电子结构、催化反应机制及反应的选择性。拟采用量子力学计算对其模型化合物的催化反应机理进行研究。并在这些研究的基础上，构建单核铜系统催化C-H键活化的价键模型。研究的目的是揭示单核铜系统的催化机制及结构活性关系，建立催化反应的微观模型。我们的研究结果将为设计新的高效铜催化剂提供重要的理论依据。

多糖单加氧酶是一类金属铜酶，能够利用氧分子或过氧化氢催化多糖的氧化降解。尽管多糖单加氧酶在全球碳素循环和工业生物质转化中有着重要作用，其催化性质并不完全清楚。本项目采用分子动力学模拟和量子力学/分子力学（QM/MM）研究金属酶催化反应机理，探讨氧分子或过氧化氢的活化机制，取得了研究成果包括：(1)弄清各种催化中心活化分子氧的机制；（2）系统分析不同配位环境对活性氧物种的几何结构和电子结构的影响，确定反应的活性物种；（3）阐明酶催化反应的详细机理，预测实验未捕捉到的关键中间体的性质；（4）揭示反应选择性的调控因素；（5）指出QM/MM的光谱模拟能够帮助确认反应瞬态中间体的结构，为进一步的理论研究提供新的思路。这些发现不仅从分子水平上揭示相关酶的催化机制，也为新型仿生催化剂的设计和开发提供理论指导。