title: The iromycins, a new family of pyridone metabolites from Streptomyces sp. I. Structure, NOS inhibitory activity, and biosynthesis.
abstract: The iromycins A-D are members of a new family of rare alpha-pyridone metabolites. The isolation and structure elucidation of these microbial secondary metabolites from Streptomyces sp. Dra 17 revealed a N-heterocyclic core structure with two unusual side chains. Iromycins act as inhibitors of nitric oxide synthases (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 set prospects for both medical therapy and basic research. Feeding experiments with 13C- and 15N -labeled precursors indicated an uncommon type of polyketide biosynthesis and clearly ruled out an isoprenoid origin. A detoxification pathway of a particular secondary metabolite in the host strain is a rare observation and here we demonstrate it with the iromycin family.
authors.affiliation: Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Tammannstrasse 2, D-37077 Göttingen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Surup
authors.forename: Oliver
authors.initials: O
authors.lastname: Wagner
authors.forename: Jan
authors.initials: J
authors.lastname: von Frieling
authors.forename: Michael
authors.initials: M
authors.lastname: Schleicher
authors.forename: Stefanie
authors.initials: S
authors.lastname: Oess
authors.forename: Peter
authors.initials: P
authors.lastname: Müller
authors.forename: Stephanie
authors.initials: S
authors.lastname: Grond
mesh_terms: D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011725:Pyridines / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D013302:Streptomyces / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D011725:Pyridines; D019001:Nitric Oxide Synthase