title: Improvement of gougerotin and nikkomycin production by engineering their biosynthetic gene clusters.
abstract: Nikkomycins and gougerotin are peptidyl nucleoside antibiotics with broad biological activities. The nikkomycin biosynthetic gene cluster comprises one pathway-specific regulatory gene (sanG) and 21 structural genes, whereas the gene cluster for gougerotin biosynthesis includes one putative regulatory gene, one major facilitator superfamily transporter gene, and 13 structural genes. In the present study, we introduced sanG driven by six different promoters into Streptomyces ansochromogenes TH322. Nikkomycin production was increased significantly with the highest increase in engineered strain harboring hrdB promoter-driven sanG. In the meantime, we replaced the native promoter of key structural genes in the gougerotin (gou) gene cluster with the hrdB promoters. The heterologous producer Streptomyces coelicolor M1146 harboring the modified gene cluster produced gougerotin up to 10-fold more than strains carrying the unmodified cluster. Therefore, genetic manipulations of genes involved in antibiotics biosynthesis with the constitutive hrdB promoter present a robust, easy-to-use system generally useful for the improvement of antibiotics production in Streptomyces.
authors.affiliation: State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Deyao
authors.initials: D
authors.lastname: Du
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhu
authors.forename: Junhong
authors.initials: J
authors.lastname: Wei
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Tian
authors.forename: Guoqing
authors.initials: G
authors.lastname: Niu
authors.forename: Huarong
authors.initials: H
authors.lastname: Tan
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D005818:Genetic Engineering; D005810:Multigene Family; D011401:Promoter Regions, Genetic; D011741:Pyrimidine Nucleosides / Q000096:biosynthesis; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D011741:Pyrimidine Nucleosides; C004942:gougerotin