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ATP-sensitive potassium channels (K(ATP)) are involved in a diverse array of physiologic functions including protection of tissue against ischemic insult, regulation of vascular tone, and modulation of insulin secretion. To improve our understanding of the role of K(ATP) in these processes, we used a gene-targeting strategy to generate mice with a(More)
Nonribosomal peptide synthetases (NRPSs) usually catalyze the biosynthesis of peptide natural products by sequential selection, activation, and condensation of amino acid precursors. It was reported that some fatty acids, α-ketoacids, and α-hydroxyacids originating from amino acid metabolism as well as polyketide-derived units can also be used by NRPS(More)
Many γ-butyrolactone-autoregulator receptors control the production of secondary metabolites in Streptomyces spp. Hence, AvaR1, an autoregulator receptor protein in Streptomyces avermitilis, was characterized as a negative regulator of avermectin (Ave) production. Deletion of AvaR1 in a high-producing strain increased production of Ave B1a approx. 1.75(More)
Analysis of naphthyridinomycin gene cluster revealed that this antibiotic is generated by nonribosomal peptide synthetase (NRPS) machinery. However, four modules encoded by two genes do not correspond with the structural units in the final product. Genetic and biochemical characterization of the gene cluster suggested that the leader peptide mechanism for(More)
The biosynthesis of antibiotics in bacteria is usually believed to be an intracellular process, at the end of which the matured compounds are exported outside the cells. The biosynthesis of saframycin A (SFM-A), an antitumor antibiotic, requires a cryptic fatty acyl chain to guide the construction of a pentacyclic tetrahydroisoquinoline scaffold; however,(More)
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