期刊
CHEMBIOCHEM
卷 16, 期 3, 页码 496-502出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201402577
关键词
antitumor agents; gene engineering; genome mining; polyketides; transcriptional regulator
资金
- Key Program of the Zhejiang Provincial Natural Science Foundation of China [LZ12C01001]
- National High Technology Research and Development Program of China (863 Program) [2012AA02A706]
- National Basic Research Program of China (973 Program) [2012CB721005]
- Specialized Research Fund for the Doctoral Program of Higher Education [20120101110143]
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.
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