Microorganisms can produce a variety of natural secondary metabolites with biological activity,which have broad application prospects in medical,agricultural and food fields. The development of molecular biology, bioinformatics and sequencing technology has laid a theoretical foundation for the mining of secondary metabolites and provided operational tools. In recent years,there are more and more studies on the secondary metabolites of microorganisms. It is difficult to get satisfactory results by traditional methods. It will be a new direction to operate microorganisms at the molecular level,such as the regulation of secondary metabolite biosynthesis gene cluster.The strategies of finding new secondary metabolites and increasing the production of secondary metabolites were reviewed,by using the methods of heterologous expression of secondary metabolite biosynthesis gene cluster,ribosome engineering,epigenetic regulation,metabolic regulation and regulation of transcription and translation level,the aim is to excavate new secondary metabolites,improve the production of secondary metabolites,and provide a breakthrough for the exploration of new drugs.