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Genome Mining‐Directed Activation of a Silent Angucycline Biosynthetic Gene Cluster in Streptomyces chattanoogensis
Author(s) -
Zhou Zhenxing,
Xu Qingqing,
Bu Qingting,
Guo Yuanyang,
Liu Shuiping,
Liu Yu,
Du Yiling,
Li Yongquan
Publication year - 2015
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201402577
Subject(s) - gene cluster , gene , biology , streptomyces albus , genome , streptomyces , genetics , computational biology , bacteria
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.