A vast number of secondary metabolites are produced in Streptomycetes under the tight control by many regulators, including two-component regulatory systems. Two-component regulatory systems with high diversity are widely distributed in Streptomycetes and perform positive or negative regulation by different and complex modes during secondary metabolites biosynthesis. Here, we reviewed some research advances on these systems involved in secondary metabolites accumulation in streptomycetes, mainly focusing on the clarification of their action modes. We also prospected the research trends in this field and application of two-component regulatory systems in the metabolic engineering of natural products.
