Genome Mining‐Directed Activation of a Silent Angucycline Biosynthetic Gene Cluster in Streptomyces chattanoogensis |
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| Authors: | Dr. Zhenxing Zhou Qingqing Xu Dr. Qingting Bu Dr. Yuanyang Guo Dr. Shuiping Liu Yu Liu Dr. Yiling Du Prof. Yongquan Li |
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| Affiliation: | 1. Institute of Biochemistry, College of Life Sciences, Zhejiang University, Zijingang Campus, 388 Yuhangtang Road, Hangzhou 310058 (China);2. College of Life Sciences, Zhejiang University, Zijingang Campus, 388 Yuhangtang Road, Hangzhou 310029 (China);3. Present address: Department of Chemistry, University of British Columbia, UBC Faculty of Science, Vancouver Campus, 2036 Main Mall, Vancouver, BC V6T 1Z1 (Canada);4. Zhejiang Provincial Key Laboratory of Microbial Biochemistry and Metabolism Engineering, Zijingang Campus, 388 Yuhangtang Road, Hangzhou 310058 (China) |
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| 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. |
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