链霉菌次级代谢调控相关的双组分系统研究进展

链霉菌具有强大的次级代谢能力, 能够产生众多具有生物活性的次级代谢产物, 如目前广泛应用的抗生素、抗肿瘤药物以及免疫抑制剂等。在链霉菌中, 次级代谢产物的生物合成受到包括途径特异性、多效性以及全局性调控基因在内的多层次严格调控。关键调控基因的缺失或过表达可以显著影响次级代谢产物的生物合成, 提示对于链霉菌次级代谢重要调控基因的功能及其作用机制的研究具有巨大的潜在应用价值。其中, 作为细菌信号传导系统的双组分系统(Two-component system, TCS)一直是大家研究的关注点。越来越多的研究表明TCS在链霉菌次级代谢过程中发挥着全局性的调控功能。本文重点介绍链霉菌模式菌株——天蓝色链霉菌中TCS(包括典型TCS)、孤立的组氨酸蛋白激酶(HK)以及应答调控蛋白(RR)参与次级代谢调控的研究进展。这些TCS的功能鉴定及机制解析为工业链霉菌的定向遗传改造以提高重要次级代谢产物的含量提供了理论依据。

Perspectives on two-component systems involved in regulation of secondary metabolism in Streptomyces

Streptomyces is characterized by its strong ability to produce an impressive array of secondary metabolites with important biological activities, such as antibiotics, anti-tumor drugs and immunosuppressors widely used clinically. In streptomycetes, the biosynthesis of secondary metabolites is under strict, multilevel regulation involving pathway-specific, pleiotropic as well as global regulators. Inactivation or overexpression of some important regulatory genes could greatly influence the production of secondary metabolites, implying that a better understanding how regulatory genes function in secondary metabolism will have great potential application values. Among them, two-component system (TCS) as the signal transduction system in bacteria has been the research focus in the past few years. Increasing evidences demonstrate that TCS plays a global regulatory role during secondary metabolic processes in Streptomyces. This review summarizes the research progress of TCS, including typical TCS, orphan histidine kinases (HKs) and response regulators (RRs), involved in the regulation of secondary metabolism in the model strain of Streptomyces, Streptomyces coelicolor. The functional identification and the mechanistic characterization of these TCS have provided a valuable theoretical basis for the directed genetic engineering to improve the yield of important secondary metabolites in industrial streptomycetes.