Abstract: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.