放线菌来源天然产物生物合成途径中P450酶的功能研究进展  

Functional Study on P450 Enzymes in the Biosynthetic Pathways of Natural Products Derived from Actinomycetes

作　　者：刘晗 陆美玲 陈依军[1] LIU Han;LU Mei-ling;CHEN Yi-jun(School of Life Science and Technology,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]中国药科大学生命科学与技术学院

出　　处：《药物生物技术》2019年第5期449-454,共6页Pharmaceutical Biotechnology

摘　　要：微生物来源的天然产物具有广泛的药用价值,其中大多数次级代谢产物的产生菌为放线菌。放线菌中普遍存在多种编码次级代谢产物的相关基因簇,其中包含大量P450蛋白家族的编码基因。此类蛋白参与次级代谢产物成熟过程中的修饰,包括氧化催化、重排等不同过程,是导致天然产物结构多样性及复杂性的重要原因之一。为适应生产及其他生物应用的需求,对P450蛋白功能等方面所进行的优化改造也受到广泛关注。文章从P450酶的基本作用机制、修饰功能、改造策略等3方面,简要概述了目前针对放线菌来源的天然产物生物合成途径中P450酶的研究,为后续通过研究P450蛋白认识新化合物合成机制,并为新药研发提供参考。Natural products derived from microorganisms have broad medicinal value,and most of the secondary metabolite-producing bacteria are actinomycetes. Gene clusters encoding secondary metabolites are ubiquitous in actinomycetes,including a large number of P450 protein-encoding genes. The involvement of such proteins in the modification during the maturation of the products,including oxidation catalysis,rear rangement and other processes,is an essential reason for the diversity and complexity of natural product structures. Thus,in order to meet the needs of production and other biological applications,the optimization of P450 protein functions and other aspects have received wide attention. This review started with the basic mechanism of P450 enzymes,and then summarized the diverse functions along with the current studies on P450 engineering through various strategies in the biosynthesis pathway of natural products derived from actinomycetes,which might provide reference for new drug discovery and development.

关 键 词：放线菌 天然产物 P450酶 机制介绍 功能研究 改造策略 

分 类 号：R379.1[医药卫生—病原生物学]