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Geninthiocins C and D from Streptomyces as 35-membered macrocyclic thiopeptides with modified tail moiety
Shufen Li1, Xinxin Hu1, Linli Li1
1NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100050, Beijing, China.
Abstract:
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-NH2, -Dha-Ala-NH2, and -NH2 tail, respectively. Besides, the Ala residue in geninthiocin C was determined as L- configuration by C3 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-NH2 tail of geninthiocin A played an important role in its potent activity against G+ bacteria.
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