Metabolic Competition between Non-reducing Polyketide Synthases Drives Hidden Chemodiversity in Deep-Sea Fungus <i>Talaromyces radicus</i>
Genome mining of <i>Talaromyces radicus</i> WHUF04045 identified two unusual nrPKSs (<i>Tr4942</i> and <i>Tr2381</i>) with distinct release mechanisms, whose precursor competition was revealed by multiomics, gene deletion, and heterologous expression. Deletion of <i>Tr4942</i> activated nine new chromone derivatives (<b>1</b>-<b>9</b>) and four new naphthoquinone derivatives (<b>11</b>-<b>14</b>), which displayed significant pro-angiogenic and anti-inflammatory activities, with compound <b>8</b> showing significant anti-inflammatory effects via modulation of the NF-κB signaling pathway.
Authors
- Wenxing Chen (ORCID: https://orcid.org/0000-0001-9669-4358)
- Jianzhong Chen (ORCID: https://orcid.org/0000-0002-8232-7298)
- Zixin Deng (ORCID: https://orcid.org/0000-0001-5668-5350)
- Lu Ke (ORCID: https://orcid.org/0000-0002-6357-7515)
- Bowei Wen
- Ning Li
- Hui Qiu
- You-Sheng Cai
- Kui Hong
- Zhicheng Guo
- Zhaoxin Yao
- Zhuoyue Yang
- Jun Wu
Institutions
- Ministry of Education of the People's Republic of China (CN)
- Qilu University of Technology (CN)
- Wuhan University (CN)
- Zhongnan Hospital of Wuhan University (CN)
- Shandong Academy of Sciences (CN)
Publication Details
- Journal
- Organic Letters
- Published
- 2026-01-29
- DOI
- https://doi.org/10.1021/acs.orglett.5c05307
- Primary Topic
- Microbial Natural Products and Biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 0.00