微生物次级代谢产物生物合成基因簇的克隆与异源表达  

Cloning and heterologous expression of biosynthetic gene clusters of microbial secondary metabolites

作　　者：李可萌 赫卫清 LI Kemeng;HE Weiqing(National Health Commission Key Laboratory of Biotechnology of Antibiotics,Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences,Beijing 100050,China)

机构地区：[1]中国医学科学院医药生物技术研究所,国家卫生健康委员会抗生素生物工程重点实验室,北京100050

出　　处：《生命的化学》2021年第3期420-427,共8页Chemistry of Life

基　　金：国家自然科学基金项目(81773617);中国医学科学院创新工程项目(2017-I2M-1-012)。

摘　　要：微生物次级代谢产物结构、功能极为多样,具有抗感染、抗肿瘤、免疫调节等多种生物活性,是新药研发的重要来源。随着新一代DNA测序技术以及生物信息学工具的快速发展,微生物基因组中大量次级代谢产物的生物合成基因簇(biosynthetic gene clusters,BGCs)被发现,BGCs克隆与异源表达在研究次级代谢产物中起着越来越关键的作用。目前,已经发展出很多新的大型BGCs克隆策略,包括TAR、Red/ET重组、DiPaC和SSR。获得的完整BGCs可以转化到适合的底盘细胞中进行异源表达,通过调控其转录水平和优化代谢途径产生新的次级代谢产物或实现目标化合物的高产。Microbial secondary metabolites are extremely diverse in chemical structures and functions,and have many biological activities,such as anti-infection,anti-tumor,immune regulation.They are important sources of new drug research and development.With the emergence of the new generation DNA sequencing technology and advanced bioinformatics tools,a large number of biosynthetic gene clusters(BGCs)of secondary metabolites in the microbial genome have been proliferated.The cloning and heterologous expression of BGCs play a key role in the exploitation of secondary metabolites.At present,many new strategies of cloning large BGCs have been developed,including TAR,Red/ET recombination,DiPaC and SSR.The cloned intact BGCs can be transformed into suitable chassis cells for heterologous expression to produce new secondary metabolites or improve yields of target compounds by regulating their transcription levels and optimizing metabolic pathways.

关 键 词：次级代谢产物 生物合成基因簇克隆 异源表达 

分 类 号：Q936[生物学—微生物学] Q78