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Peer-reviewed veterinary case report

Anti-Inflammatory α-Pyrone Polyethers Generated by Interrupting the Enolized 1,3-Diketone Formation in the Polyketide Synthases of Calcium-Ionophore Ionomycin.

Journal:
Organic letters
Year:
2025
Authors:
Li, Mengjia et al.
Affiliation:
Department of Pharmacy · China

Abstract

Carboxyl polyethers fromhave 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 geneJ 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.

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Original publication: https://pubmed.ncbi.nlm.nih.gov/39965537/