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 Δ21,26 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.

A New Thiopeptide Antibiotic, Micrococcin P3, from a Marine-Derived Strain of the Bacterium Bacillus stratosphericus

“…The NOE correlation between H-8 and H-9 showed the same intensity for both compounds, while the NOE correlation between H-44 and H-45 was not observed at all for compound 1 , but was clearly observed for compound 2 ( Figure S2 ). These observations indicated a 42 E configuration for the Dhb-Thia 5 unit of compound 1 , which is different from the 42 Z configuration of 2 [ 7 ].…”

Streptomonospora litoralis sp. nov., a halophilic thiopeptides producer isolated from sand collected at Cuxhaven beach

“…In frame of an investigation of the secondary metabolite production capacity of rare Actinobacteria obtained from beach sands, strain M2 T was isolated from a sand sample collected at Cuxhaven, North Sea, Germany (53°52 0 39.5 00 N, 8°41 0 22.4 00 E) on 20 th of July 2017. In our preceding study, we showed that M2 T produces the two new thiopeptides litoralimycin 1 (A) and 2 (B) with cytotoxic activity (Khodamoradi et al 2020). Here, we report on the description of new Streptomonospora species with the type strain M2.…”

“…The remaining BGCs were predicted to encode three polyketides, one nonribosomal peptide, one lanthipeptide, and one ectoine (Figure S5). As outlined above, M2 T has been shown to produce the thiopeptides litoralimycin A and B (Khodamoradi et al 2020), as well as sulfomycin I, methylsulfomycin and sulfomycin III. Gene cluster region 4 detected by antiSMASH analysis harbors a predicted thiopeptide BGC (BGC4), which is expected to code for the thiopeptide biosynthesis of M2 T (Figure S5).…”

“…In a previous study, we isolated two new cytotoxic compounds, named litoralimycin A and B from strain M2 T (Khodamoradi et al 2020). However, the production of litoralimycins 1 and 2 could not explain the observed antibacterial properties of crude extracts of strain M2 T against the Gram-positive bacteria, since these thiopeptides do not possess antibacterial properties.…”

“…globisporus with a difference of only two amino acids (Figure S7b). Due to the structural similarity of the litoralimycins with radamycin (Khodamoradi et al 2020), it can be expected that Lit12 encodes the peptide precursor for litoralimycin biosynthesis in M2 T .…”