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Svetamycins A–G, Unusual Piperazic Acid-Containing Peptides from Streptomyces sp.

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journal contribution
posted on 10.05.2017, 00:00 by Denis Dardić, Gianluigi Lauro, Giuseppe Bifulco, Patricia Laboudie, Peyman Sakhaii, Armin Bauer, Andreas Vilcinskas, Peter E. Hammann, Alberto Plaza
Seven new halogenated peptides termed svetamycins A–G (17) 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 γ-halogenated piperazic acid, and a novel δ-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 δ 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 μg/mL.