Genome Mining Guided Discovery of Macrocyclic Sesterterpenoids with Anti-MRSA and Anti-Neuroinflammatory Activities
Terpenoids exhibit antioxidant, antimicrobial, and health-promoting activities, and are widely utilized in the food industry. In this study, a new bifunctional terpene synthase (BFTPS) and its associated gene cluster were identified in <i>Colletotrichum cereale</i> 00173 through a genome mining approach. Heterologous expression of the BFTPS and its gene cluster in <i>Aspergillus oryzae</i> NSAR1 led to the production of a 14-membered macrocyclic sesterterpene, colcerepene (<b>1</b>), and four hydroxylated derivatives, colcerepenoids A-D (<b>2</b>-<b>5</b>). The biosynthetic pathway of compounds <b>1</b>-<b>5</b> was further elucidated through feeding experiments. Notably, compound <b>1</b> exhibited antibacterial activity against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) with an MIC value of 6.25 μM. This study is the first report of <i>anti</i>-MRSA activity in macrocyclic sesterterpenoids, expanding the functional space of macrocyclic sesterterpenoids as promising leads for developing agents against foodborne pathogens.
Authors
- Kangjie Lv
- Cui-Ping Xing
- Xiaobo Mao (ORCID: https://orcid.org/0000-0001-6587-556X)
- Guoliang Zhu (ORCID: https://orcid.org/0000-0002-6628-8874)
- Weijie Wu (ORCID: https://orcid.org/0000-0002-4894-5981)
- Xueting Liu (ORCID: https://orcid.org/0000-0002-1322-8253)
- Lan Jiang (ORCID: https://orcid.org/0000-0002-4097-1341)
- Zhennan Wang (ORCID: https://orcid.org/0000-0003-4883-2538)
- Tom Hsiang (ORCID: https://orcid.org/0000-0002-9549-1847)
- Yuwei Chen
- Huanqin Dai (ORCID: https://orcid.org/0000-0002-8108-815X)
- Xiaoying Li (ORCID: https://orcid.org/0000-0001-6449-1505)
- Lixin Zhang (ORCID: https://orcid.org/0000-0003-0268-6774)
- Qiang Yin
- Xuming Mo
- Keying Lan
Institutions
- Nanjing Tech University (CN)
- East China University of Science and Technology (CN)
- Johns Hopkins University (US)
- Chinese Academy of Sciences (CN)
- Johns Hopkins Medicine (US)
- Alpha Technologies (Canada) (CA)
- Czech Academy of Sciences, Institute of Microbiology (CZ)
- Ministry of Health (OM)
- Institute of Microbiology (CN)
- Second Affiliated Hospital of Nanjing Medical University (CN)
- Pharmaceutical Biotechnology (Czechia) (CZ)
- State Key Laboratory of Reproductive Medicine
- State Key Laboratory of Bioreactor Engineering
- University of Guelph (CA)
- Nanjing Medical University (CN)
Publication Details
- Journal
- Journal of Agricultural and Food Chemistry
- Published
- 2025-12-14
- DOI
- https://doi.org/10.1021/acs.jafc.5c11512
- Primary Topic
- Plant biochemistry and biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 0.00