Litoralimycins A and B, new cytotoxic thiopeptides from streptomonospora sp. M2

Abstract

Streptomonospora sp. M2 has been isolated from a soil sample collected at the Wadden Sea beach in our ongoing program aimed at the isolation of rare Actinobacteria, ultimately targeting the discovery of new antibiotics. Because crude extracts derived from cultures of this strain showed inhibitory activity against the indicator organism Bacillus subtilis, it was selected for further analysis. HPLC–MS analysis of its culture broth revealed the presence of lipophilic metabolites. The two major metabolites of those were isolated by preparative reversed-phase HPLC and preparative TLC. Their planar structures were elucidated using high-resolution electrospray ionization mass spectrometry (HRESIMS), 1D and 2D NMR data as new thiopeptide antibiotics and named litoralimycin A (1) and B (2). Although rotating frame nuclear Overhauser effect spectroscopy (ROESY) data established a Z configuration of the ∆21,26 double bond, the stereochemistry of C-5 and C-15 were assigned as S by Marfey’s method after ozonolysis. The biological activity spectrum of 1 and 2 is highly uncommon for thiopeptide antibiotics, since they showed only insignificant antibacterial activity, but 1 showed strong cytotoxic effects.