细胞色素P450酶在生物合成及有机合成中的催化功能及其应用

Catalytic Function and Application of Cytochrome P450 Enzymes in Biosynthesis and Organic Synthesis

细胞色素P450酶分布广泛,主要参与生物体外源物质代谢与天然产物生物合成,能以结构多样的有机化合物作为底物催化多种类型的化学反应.P450酶可在温和条件下实现底物分子中C—H键的选择性氧化,因而在精细化学品、化学中间体及药物分子的生产上具有很高的实用价值及多年的应用历史.随着蛋白质工程、氧化还原伴侣工程、底物工程、代谢工程与合成生物学的发展,目前已可初步实现根据反应需求来理性设计或定向进化改造P450酶催化系统来高效催化多种有机反应,拓宽了P450酶在生物合成与有机合成反应中的应用范围.总结了近年来由细胞色素P450酶参与催化的主要反应类型,归纳了拓宽P450酶催化反应类型、提高催化活性和选择性的一些重要策略,并对未来P450酶在生物合成及有机合成反应中的应用发展前景和挑战进行了展望.

Cytochrome P450 enzymes are widely distributed in nature, which mainly participate in xenobiotics metabolism and natural product biosynthesis. These enzymes are able to recognize various substrates to produce many useful oxidative products through diverse reaction types. P450 enzymes can catalyze selective oxidation of C—H bonds in their substrates under mild conditions. Therefore, a lot of P450 enzymes have been applied in the production of fine chemicals, drugs and chemical intermediates for quite a long time. With the development of protein engineering, redox partner engineering, substrate engineering, metabolic engineering and synthetic biology, it has become possible to obtain the P450 biocatalysts with the desired properties such as high activity, the substrate specificity of interest, and great selectivity to meet the industrial requirements, through rational design and direct evolution of P450 enzymes. Thus, the application scope of P450 enzymes in biosynthesis and organic synthesis has been expanded greatly. The types of reactions that can be catalyzed by P450 enzymes, and the strategies to broaden the reaction scope and to enhance the catalytic efficiency and selectivity are summarized. Finally, the challenges and prospects in the application of cytochrome P450 enzymes in biosynthesis and organic synthesis are discussed.