Dardic, D.D.DardicLauro, G.G.LauroBifulco, G.G.BifulcoLaboudie, P.P.LaboudieSakhaii, P.P.SakhaiiBauer, A.A.BauerVilcinskas, A.A.VilcinskasHammann, P.E.P.E.HammannPlaza, A.A.Plaza2022-03-052022-03-052017https://publica.fraunhofer.de/handle/publica/24928910.1021/acs.joc.7b00228Seven new halogenated peptides termed svetamycins A-G (1-7) have been isolated from laboratory cultures of a Streptomyces sp. Svetamycins A-D, F, and G are cyclic depsipeptides, whereas svetamycin E is a linear analogue of svetamycin C. Their structures were determined using extensive spectroscopic analysis, and their stereochemical configuration was established by a combination of NMR data, quantum mechanical calculations, and chemical derivatizations. Svetamycins are characterized by the presence of a hydroxyl acetic acid and five amino acids including a rare 4,5-dihydroxy-2,3,4,5-tetrahydropyridazine-3-carboxylic acid, a g-halogenated piperazic acid, and a novel d-methylated piperazic acid in svetamycins B-C, E, and G. Moreover, isotope-labeled substrate feeding experiments demonstrated ornithine as the precursor of piperazic acid and that methylation at the d position of the piperazyl scaffold is S-adenosyl-l-methionine (SAM)-dependent. Svetamycin G, the most potent antimicrobial of this suite of compounds, inhibited the growth of Mycobacterium smegmatis with an MIC80 value of 2 mg/mL.en540journal article