萜类合成酶定向进化的新思路  

Innovations for directed evolution of terpenoid synthases

作　　者：胡智慧[1] 翁彦如 谌柄旭 于爱群 肖冬光[1] Zhihui Hu;Yanru Weng;Bingxu Chen;Aiqun Yu;Dongguang Xiao(Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science & Technology, Tianjin Engineering Research Center of Microbial Metabolism and Fermentation Process Control, Tianjin 300457, China)

机构地区：[1]天津科技大学生物工程学院教育部工业发酵微生物重点实验室微生物代谢与发酵过程控制技术工程中心,天津300457

出　　处：《微生物学报》2019年第4期591-600,共10页Acta Microbiologica Sinica

基　　金：天津市教委科研计划项目(2017ZD03);天津市自然科学基金(17JCYBJC40800);天津科技大学"海河学者"培育计划引进人才基金;南开大学分子微生物学与技术教育部重点实验室开放课题;天津市高等学校创新团队培养计划资助(TD13-5013);天津市科学技术委员会创新平台项目(17PTGCCX00190)~~

摘　　要：萜类化合物是天然产物中种类最多且主要存在于植物和微生物体内的一类化合物。随着越来越多具有应用价值的萜类化合物被挖掘,其应用前景引起了人们的关注,但由于含量低、提取成本高等缺点,因此制约了萜类化合物的广泛应用。合成生物学的兴起,为异源合成具有应用价值的萜类化合物提供了新思路,使构建定向、高效的微生物细胞工厂成为现实。萜类合成酶常作为萜类化合物异源合成代谢调控的靶酶,但天然的萜类合成酶存在催化效率低、底物专一性差、立体/区域选择性差、稳定性差等问题,严重影响萜类化合物的产量。萜类合成酶的定向进化可以有效地解决上述问题,为实现微生物细胞工厂异源、高效合成萜类化合物奠定基础。本文综述了近年来酶的定向进化技术的最新进展及应用,并提出了萜类合成酶定向进化的策略。Terpenoids are mostly existing compounds in natural products like plants and microorganisms. The application prospect of terpenoids attracts much attention owing to more and more valuable terpenoids discovered. However, limited yield and high extraction cost of terpenoids restrict their wide applications. The rise of synthetic biology has provided new ideas for biosynthesis of valuable terpenoids using targeted and high efficient microbial cell factories. Although terpenoid synthases are widely used as target enzymes in metabolic regulation of terpenoids biosynthesis, many natural terpenoid synthases have some disadvantages, such as insufficient catalytic activity, poor substrate specificity, poor regio-or stereoselectivity, poor stability and so on,which unfavorably affect the yield of terpenoids. To solve above problems, directed evolution of terpenoid synthases has been applied, which will have profound impact on biosynthesis of terpenoids by microbial cell factories. This review summarizes recent advances and their applications in directed evolution of enzymes.Meanwhile, the strategies for directed evolution of terpenoid synthases are proposed.

关 键 词：萜类化合物 萜类合成酶 合成生物学 定向进化 

分 类 号：Q814[生物学—生物工程]