Geninthiocins C and D from Streptomyces as 35-membered macrocyclic thiopeptides with modified tail moiety.

Geninthiocin is a thiopeptide with 35-membered macrocyclic core moiety. It has potent anti-Gram-positive (G) bacteria activity. Herein, we reported two new congeners (2-3) of geninthiocin (geninthiocin A, 1) from Streptomyces sp. CPCC 200267, and designated them as geninthiocins C and D, whose structures were determined by NMR. Geninthiocins A, C and D had the same 35-membered macrocyclic core moiety, but possessed a -Dha-Dha-NH, -Dha-Ala-NH, and -NH tail, respectively. Besides, the Ala residue in geninthiocin C was determined as L- configuration by C Marfey's method. In vitro assays indicated that geninthiocins C-D showed no antibacterial activity, in contrast to the potent anti-G bacteria activity displayed by geninthiocin A. Therefore, the -Dha-Dha-NH tail of geninthiocin A played an important role in its potent activity against G bacteria.