title: Genome mining-directed activation of a silent angucycline biosynthetic gene cluster in Streptomyces chattanoogensis.
abstract: Genomic sequencing of actinomycetes has revealed the presence of numerous gene clusters seemingly capable of natural product biosynthesis, yet most clusters are cryptic under laboratory conditions. Bioinformatics analysis of the completely sequenced genome of Streptomyces chattanoogensis L10 (CGMCC 2644) revealed a silent angucycline biosynthetic gene cluster. The overexpression of a pathway-specific activator gene under the constitutive ermE* promoter successfully triggered the expression of the angucycline biosynthetic genes. Two novel members of the angucycline antibiotic family, chattamycins A and B, were further isolated and elucidated. Biological activity assays demonstrated that chattamycin B possesses good antitumor activities against human cancer cell lines and moderate antibacterial activities. The results presented here provide a feasible method to activate silent angucycline biosynthetic gene clusters to discover potential new drug leads.
authors.affiliation: Institute of Biochemistry, College of Life Sciences, Zhejiang University, Zijingang Campus, 388 Yuhangtang Road, Hangzhou 310058 (China).
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Zhou
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Xu
authors.forename: Qingting
authors.initials: Q
authors.lastname: Bu
authors.forename: Yuanyang
authors.initials: Y
authors.lastname: Guo
authors.forename: Shuiping
authors.initials: S
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Yiling
authors.initials: Y
authors.lastname: Du
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Li
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology; D001551:Benz(a)Anthracenes / Q000737:chemistry / Q000494:pharmacology; D003198:Computer Simulation; D057225:Data Mining / Q000379:methods*; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D006027:Glycosides / Q000096:biosynthesis* / Q000737:chemistry; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D015394:Molecular Structure; D005810:Multigene Family; D009844:Oligosaccharides / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D001551:Benz(a)Anthracenes; D006027:Glycosides; D009844:Oligosaccharides; C000601691:chattamycin A; C000601692:chattamycin B
keywords: antitumor agents; gene engineering; genome mining; polyketides; transcriptional regulator