Anti-Inflammatory α-Pyrone Polyethers Generated by Interrupting the Enolized 1,3-Diketone Formation in the Polyketide Synthases of Calcium-Ionophore Ionomycin
Carboxyl polyethers from <i>Actinomycetes</i> have diverse bioactivities, being biosynthesized by type-I polyketide synthetases. Of them, ionomycin, the commercial calcium ionophore, bears a unique enolized 1,3-diketone moiety. Herein, mutagenetic analysis of ionomycin biosynthesis revealed a rare dehydrogenase gene <i>ino</i>J putatively involved in enol moiety formation. Interruption of the enolized 1,3-diketone formation by inactivating a ketoreductase domain yielded the first natural polyether with an α-pyrone ring, which was demonstrated with significant anti-inflammatory activity in a mouse colitis model.
Authors
- Li‐Li Hong (ORCID: https://orcid.org/0000-0003-1457-5158)
- Yongjun Zhou (ORCID: https://orcid.org/0000-0002-3005-2843)
- Hou‐Wen Lin (ORCID: https://orcid.org/0000-0002-7097-0876)
- Wei‐Hua Jiao (ORCID: https://orcid.org/0000-0003-4835-4775)
- Mengjia Li (ORCID: https://orcid.org/0000-0002-0336-5166)
- Jing Xu (ORCID: https://orcid.org/0000-0002-3307-2719)
- Wanlu Li (ORCID: https://orcid.org/0000-0003-2677-2765)
- Chang Xu (ORCID: https://orcid.org/0000-0003-2674-0034)
- Haixia Zang
- Wen-Rui Peng
Institutions
- Shanghai Jiao Tong University (CN)
- Renji Hospital (CN)
Publication Details
- Journal
- Organic Letters
- Published
- 2025-02-18
- DOI
- https://doi.org/10.1021/acs.orglett.4c04711
- Primary Topic
- Synthetic Organic Chemistry Methods
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- National Key Research and Development Program of China