Antibacterial and cytotoxic angucyclines discovered by heterologous expression of a type II polyketide gene cluster
Three new aromatic polyketides, spirocyclione C (1) and angumycinones E and F (2 and3), were isolated from the heterologous expression of a type II gene cluster in the strain of <i>Streptomyces coelicolor</i> A3(2) assisted by the one strain many compounds (OSMAC) strategy. The structures and absolute configurations of these compounds were elucidated by extensive NMR, MS, theoretical NMR calculations, DP4+ probability analysis, and ECD analyses. Notably, compound 1 represents the first example of an angucycline structure with an unusual oxaspiro[5.4]undecane architecture. Directed by molecular docking and dynamics simulations, the bioactivities of compounds 1-3 were evaluated. Compounds 1 and 2 exhibited promising cytotoxic activity against a panel of human cancer cell lines, and compound 1 showed moderate antibacterial activity against clinical pathogenic strains of <i>B. subtilis</i>, <i>P. vulgaris</i>, <i>B. cereus</i>, <i>M. phlei</i> and MRSA.
Authors
- Qian Che (ORCID: https://orcid.org/0000-0003-0610-1593)
- Xinchen Yue
- Tianjiao Zhu (ORCID: https://orcid.org/0000-0003-4185-5593)
- Guojian Zhang (ORCID: https://orcid.org/0000-0002-4976-8083)
- Dehai Li (ORCID: https://orcid.org/0000-0002-7191-2002)
- Hengyi Xu (ORCID: https://orcid.org/0000-0001-9809-4882)
- Falei Zhang (ORCID: https://orcid.org/0000-0002-0208-8232)
- Donghe Lan
- Xu Xiao (ORCID: https://orcid.org/0000-0002-4500-4107)
- Xiaoting Zhang (ORCID: https://orcid.org/0000-0003-2157-8381)
- Jiayi Li (ORCID: https://orcid.org/0000-0001-8007-4138)
- Lang Wang (ORCID: https://orcid.org/0009-0008-3797-1077)
Institutions
- Qingdao National Laboratory for Marine Science and Technology (CN)
- Marine Biomedical Research Institute of Qingdao (CN)
- Ocean University of China (CN)
Publication Details
- Journal
- Organic & Biomolecular Chemistry
- Published
- 2025-01-01
- DOI
- https://doi.org/10.1039/d5ob00190k
- Citations
- 1
- Primary Topic
- Microbial Natural Products and Biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 1.39
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Shandong Province
- National Natural Science Foundation of China-Shandong Joint Fund
- National Key Research and Development Program of China
- Fundamental Research Funds for the Central Universities