Diasperonins A–F: Anti-inflammatory Aspertetronin Dimers Discovered via BBMN and Heterologous Expression Strategy
By integrating heterologous expression of the entire biosynthetic gene cluster in <i>Aspergillus nidulans</i> and a building blocks-based molecular networking (BBMN) strategy, six novel aspertetronin dimers (diasperonins A-F, <b>1-6</b>) with three unprecedented skeletons and two additional novel congeners (<b>7-8</b>) were characterized from the engineered strain. High monomer levels from gene cluster overexpression likely triggered nonenzymatic dimerization. Compound <b>7</b> suppressed the NF-κB pathway in LPS-induced RAW264.7 cells and mouse model, demonstrating potent anti-inflammatory activity.
Authors
- Zhengxi Hu (ORCID: https://orcid.org/0000-0002-1247-5615)
- Shuang Lin (ORCID: https://orcid.org/0000-0001-7251-4113)
- Wen‐Bing Yin (ORCID: https://orcid.org/0000-0002-9184-3198)
- Yuben Qiao (ORCID: https://orcid.org/0000-0002-8881-1232)
- Yuan Zhou (ORCID: https://orcid.org/0000-0003-2892-0100)
- Fei Cao
- Jingwen Yu (ORCID: https://orcid.org/0000-0002-7374-3185)
- Yonghui Zhang (ORCID: https://orcid.org/0000-0002-7222-2142)
- Ying Ye (ORCID: https://orcid.org/0009-0008-1505-3937)
- Chunmei Chen (ORCID: https://orcid.org/0000-0003-2087-7769)
- Hucheng Zhu (ORCID: https://orcid.org/0000-0002-6672-0014)
- Xiaotian Zhang
- Yuanyang Peng
- Weiguang Sun
- Chenyang Wang (ORCID: https://orcid.org/0009-0004-1770-1011)
- Hao Wang (ORCID: https://orcid.org/0009-0008-4494-6793)
Institutions
- Chinese Academy of Sciences (CN)
- Culture Resource (EG)
- Czech Academy of Sciences, Institute of Microbiology (CZ)
- Ecologie microbienne (FR)
- Hebei University (CN)
- Huazhong University of Science and Technology (CN)
- The University of Tokyo (JP)
- Hubei University (CN)
Publication Details
- Journal
- Organic Letters
- Published
- 2025-05-20
- DOI
- https://doi.org/10.1021/acs.orglett.5c01397
- Citations
- 4
- Primary Topic
- Metabolomics and Mass Spectrometry Studies
- Type
- article
- Field-Weighted Citation Impact
- 3.22
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Hubei Province
- China Scholarship Council
- National Key Research and Development Program of China
- National Program for Support of Top-notch Young Professionals
- Science and Technology Program of Hubei Province