Abstract:Biosynthetic pathway genes for each natural product are mostly located together on a large and continuous segment of the genome to compose a gene cluster. Actinobacteria genomes usually contain various natural product biosynthetic gene clusters, which are valuable resources of potential applications in medicine, agriculture and industry. Some of these gene clusters are considered to be silent because no related metabolites could be detected under laboratory conditions. For functional analyses of natural product biosynthetic gene clusters, researchers constructed a lot of high-capacity vectors and many heterologous hosts by genetic engineering for cloning and expressing large DNA fragments of actinobacteria genomes in the last two decades.