Genome Mining and Heterologous Expression-Guided Discovery of Mangicol Sesterterpenoids with Antimicrobial and Antineuroinflammatory Activities
The accelerating increase in antimicrobial resistance presents serious dangers to global health, food safety, and agricultural productivity. In this study, we explored fungal-derived sesterterpenoids as potential antimicrobial agents, focusing on mangicols biosynthesized by a newly identified bifunctional terpene synthase from <i>Fusarium oxysporum</i> 14005. By combination of genome mining, heterologous pathway reconstitution, and feature-based molecular networking, eight new mangicols featuring epoxy and tetrahydrofuran moieties on their side chains were identified and characterized. Antimicrobial assays revealed that several of these derivatives exhibited potent activity against <i>Ralstonia solanacearum</i>, <i>Staphylococcus aureus</i>, and <i>Streptococcus mutans</i>, with minimum inhibitory concentrations ranging from 6.25 to 25 μM. Furthermore, compounds <b>3</b>-<b>5</b> demonstrated significant antineuroinflammatory effects in murine BV2 microglial cells with 50.0, 53.13, and 48.05%, respectively. The results offer mechanistic insights into the biosynthesis and bioactivity of mangicol-type sesterterpenoids and support their potential as novel antimicrobial and anti-inflammatory agents for addressing antimicrobial resistance.
Authors
- Kangjie Lv
- Cui-Ping Xing
- Lan Jiang (ORCID: https://orcid.org/0000-0003-2778-1081)
- Guoliang Zhu (ORCID: https://orcid.org/0000-0002-6628-8874)
- Huanting Yang
- Xueting Liu (ORCID: https://orcid.org/0000-0002-1322-8253)
- Tom Hsiang (ORCID: https://orcid.org/0000-0002-9549-1847)
- Huanqin Dai (ORCID: https://orcid.org/0000-0002-8108-815X)
- Wael M. Abdel‐Mageed (ORCID: https://orcid.org/0000-0002-8130-684X)
- Lixin Zhang (ORCID: https://orcid.org/0000-0003-0894-9520)
- Biao Ren (ORCID: https://orcid.org/0000-0003-4215-2873)
- Bin Zhu (ORCID: https://orcid.org/0000-0003-1085-1231)
- Xuming Mo
- Yi Jiang (ORCID: https://orcid.org/0000-0002-3674-3346)
- Keying Lan
- Cheng‐Lin Jiang
Institutions
- East China University of Science and Technology (CN)
- Yunnan University (CN)
- Chinese Academy of Sciences (CN)
- Sichuan University (CN)
- National Clinical Research Center for Digestive Diseases (CN)
- Czech Academy of Sciences, Institute of Microbiology (CZ)
- Institute of Microbiology (CN)
- Second Affiliated Hospital of Nanjing Medical University (CN)
- Pharmac (NZ)
- State Key Laboratory of Oral Diseases
- State Key Laboratory of Bioreactor Engineering
- University of Guelph (CA)
- Assiut University (EG)
Publication Details
- Journal
- Journal of Agricultural and Food Chemistry
- Published
- 2025-07-24
- DOI
- https://doi.org/10.1021/acs.jafc.5c04187
- Primary Topic
- Plant biochemistry and biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Science and Technology Commission of Shanghai Municipality
- State Key Laboratory of Bioreactor Engineering
- Higher Education Discipline Innovation Project
- National Key Research and Development Program of China