The Iromycins, a New Family of Pyridone Metabolites from Streptomyces sp. I. Structure, NOS Inhibitory Activity, and Biosynthesis

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• 作者：Frank Surup ; Oliver Wagner ; Jan von Frieling ; Michael Schleicher ; Stefanie Oess ; Peter Mü ; ller ; Stephanie Grond
• 刊名：Journal of Organic Chemistry
• 出版年：2007
• 出版时间：July 6, 2007
• 年：2007
• 卷：72
• 期：14
• 页码：5085 - 5090
• 全文大小：295K
• 年卷期：v.72,no.14(July 6, 2007)
• ISSN：1520-6904

文摘

The iromycins A-D are members of a new family of rare -pyridone metabolites. The isolation andstructure elucidation of these microbial secondary metabolites from Streptomyces sp. Dra 17 revealed aN-heterocyclic core structure with two unusual side chains. Iromycins act as inhibitors of nitric oxidesynthases (NOS), a protein family, which produces the crucial second messenger nitric oxide (NO).Importantly, these compounds inhibit selectively endothelial NOS rather than neuronal NOS and thus setprospects for both medical therapy and basic research. Feeding experiments with ¹³C- and ¹⁵N -labeledprecursors indicated an uncommon type of polyketide biosynthesis and clearly ruled out an isoprenoidorigin. A detoxification pathway of a particular secondary metabolite in the host strain is a rare observationand here we demonstrate it with the iromycin family.