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

IF 4.9 1区化学 Q1 CHEMISTRY, ORGANIC

Organic Letters Pub Date : 2025-02-18 DOI:10.1021/acs.orglett.4c04711

Mengjia Li, Jing Xu, Haixia Zang, Wen-Rui Peng, Li-Li Hong, Chang Xu, Wanlu Li, Wei-Hua Jiao, Hou-Wen Lin, Yongjun Zhou

引用次数: 0

Abstract

Carboxyl polyethers from Actinomycetes 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 inoJ 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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来源期刊

Organic Letters 化学-有机化学

CiteScore

9.30

自引率

11.50%

发文量

1607

审稿时长

1.5 months

期刊介绍： Organic Letters invites original reports of fundamental research in all branches of the theory and practice of organic, physical organic, organometallic,medicinal, and bioorganic chemistry. Organic Letters provides rapid disclosure of the key elements of significant studies that are of interest to a large portion of the organic community. In selecting manuscripts for publication, the Editors place emphasis on the originality, quality and wide interest of the work. Authors should provide enough background information to place the new disclosure in context and to justify the rapid publication format. Back-to-back Letters will be considered. Full details should be reserved for an Article, which should appear in due course.