Metabolic Engineering Strategies Based on Secondary Messengers c-di-GMP for the Discovery of Novel Aromatic Polyketides in <i>Streptomyces</i> sp. HDN154049
Four unreported aromatic polyketides CA049 A-D (<b>1</b>-<b>4</b>) were discovered in <i>Streptomyces</i> sp. HDN154049 through CdgB overexpression, an enzyme involved in c-di-GMP biosynthesis. Among them, compound <b>1</b> contains a novel tricyclic aromatic scaffold appended with an α-pyranone ring, while compound <b>3</b> represents the first example of a benzo-[<i>kl</i>]-xanthene skeleton derived from microbiological sources, and it displayed cytotoxic activity against the L-02 cancer cell line (IC<sub>50</sub> = 6.71 μM). This work shows that adjusting the expression level of c-di-GMP could be an efficient method to increase the secondary metabolic production capacity of actinomycete strains.
Authors
- Qian Che (ORCID: https://orcid.org/0000-0003-0610-1593)
- 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)
- Falei Zhang (ORCID: https://orcid.org/0000-0002-0208-8232)
- Xiaoting Zhang (ORCID: https://orcid.org/0000-0003-2157-8381)
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
- ACS Omega
- Published
- 2025-06-19
- DOI
- https://doi.org/10.1021/acsomega.5c02178
- 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
- Taishan Scholar Project of Shandong Province
- National Key Research and Development Program of China
- Fundamental Research Funds for the Central Universities