细胞色素P450酶与微生物药物创制  

Cytochrome P450 enzymes and microbial drug development

作　　者：李众[1,2] 张伟[1] 李盛英[1] 

机构地区：[1]中国科学院青岛生物能源与过程研究所,山东省合成生物学省级重点实验室,中国科学院生物燃料重点实验室,山东青岛266101 [2]中国科学院大学,北京100049

出　　处：《微生物学报》2016年第3期496-515,共20页Acta Microbiologica Sinica

基　　金：国家自然科学基金(31422002,31300075);山东省自然科学基金(JQ201407)~~

摘　　要：细胞色素P450酶广泛存在于动植物和微生物体内,具有底物结构多样性和催化反应类型多样性,在天然产物生物合成中扮演重要作用。P450酶可在温和条件下高选择性地催化结构复杂有机化合物中惰性C-H键的氧化反应,具备化学催化剂难以比拟的优势,因此在微生物制药领域具有广阔的应用空间。本文综述了参与天然产物生物合成的P450酶近年来的研究进展;P450酶的酶工程改造、生物转化实践及其在微生物药物创制方面的应用现状;探讨了P450酶的工业应用瓶颈及其解决途径;并对P450酶未来的应用前景进行了展望。Cytochrome P450 enzymes broadly exist in animals, plants and microorganisms. This superfamily of monooxygenases holds the greatest diversity of substrate structures and catalytic reaction types among all enzymes.P450 enzymes play important roles in natural product biosynthesis. In particular, P450 enzymes are capable of catalyzing the regio- and stereospecific oxidation of non-activated C-H bonds in complex organic compounds under mild conditions, which overrides many chemical catalysts. This advantage thus warrants their great potential in microbial drug development. In this review, we introduce a variety of P450 enzymes involved in natural product biosynthesis; provide a brief overview on protein engineering, biotransformation and practical application of P450enzymes; and discuss the limits, challenges and prospects of industrial application of P450 enzymes.

关 键 词：细胞色素P450酶 微生物制药 酶工程 生物转化 

分 类 号：R915[医药卫生—微生物与生化药学] Q559.9[医药卫生—药学]