Lobophorin K, a new natural product with cytotoxic activity produced by Streptomyces sp. M-207 associated with the deep-sea coral Lophelia pertusa

The present article describes the isolation of a new natural product of the lobophorin family, designated as lobophorin K (1), from cultures of the marine actinobacteria Streptomyces sp. M-207, previously isolated from the cold-water coral Lophelia pertusa collected at 1800 m depth during an expedition to the submarine Avilés Canyon. Its structure was determined using a combination of spectroscopic techniques, mainly ESI-TOF MS and 1D and 2D NMR. This new natural product displayed cytotoxic activity against two human tumor cell lines, such as pancreatic carcinoma (MiaPaca-2) and breast adenocarcinoma (MCF-7). Lobophorin K also displayed moderate and selective antibiotic activity against pathogenic Gram-positive bacteria such as Staphylococcus aureus

Atmospheric Precipitations, Hailstone and Rainwater, as a Novel Source of Streptomyces Producing Bioactive Natural Products

A cultivation-dependent approach revealed that highly diverse populations of Streptomyces were present in atmospheric precipitations from a hailstorm event sampled in February 2016 in the Cantabrian Sea coast, North of Spain. A total of 29 bioactive Streptomyces strains isolated from small samples of hailstone and rainwater, collected from this hailstorm event, were studied here. Taxonomic identification by 16S rRNA sequencing revealed more than 20 different Streptomyces species, with their closest homologs displaying mainly oceanic but also terrestrial origins. Backward trajectory analysis revealed that the air-mass sources of the hailstorm event, with North Western winds, were originated in the Arctic Ocean (West Greenland and North Iceland) and Canada (Labrador), depending on the altitude. After traveling across the North Atlantic Ocean during 4 days the air mass reached Europe and precipitated as hailstone and rain water at the sampling place in Spain. The finding of Streptomyces species able to survive and disperse through the atmosphere increases our knowledge of the biogeography of genus Streptomyces on Earth, and reinforces our previous dispersion model, suggesting a generalized feature for the genus which could have been essential in his evolution. This unique atmospheric-derived Streptomyces collection was screened for production of bioactive secondary metabolites. Analyses of isolates ethyl acetate extracts by LC-UV-MS and further database comparison revealed an extraordinary diversity of bioactive natural products. One hundred molecules were identified, mostly displaying contrasted antibiotic and antitumor/cytotoxic activities, but also antiparasitic, antiviral, anti-inflammatory, neuroprotector, and insecticide properties. More interestingly, 38 molecules not identified in natural products databases might represent new natural products. Our results revealed for the first time an extraordinary diversity of Streptomyces species in the atmosphere able to produce an extraordinary repertoire of bioactive molecules, thus providing a very promising source for the discovery of novel pharmaceutical natural products

New 3-Hydroxyquinaldic Acid Derivatives from Cultures of the Marine Derived Actinomycete Streptomyces cyaneofuscatus M-157

Fractionation of the bioactive extract of a culture of the marine derived actinomycete Streptomyces cyaneofuscatus M-157 led to the isolation of the known 3-hydroxyquinaldic acid (4), its amide (5) and three new derivatives (1–3) containing different amino acid residues. The structures of the new molecules (1–3), including their absolute configuration, were determined by the analysis of their ESI-TOF MS and one-dimensional (1D) and two-dimensional (2D) NMR spectra and advanced Marfey’s analysis of their hydrolyzation products. Compound 3 spontaneously dimerized in solution to give the disulfide derivative 6. Unfortunately, none of the new compounds isolated confirmed the antimicrobial activity found in the bacterial extract, perhaps indicating that such antibacterial activity might be due to presence in the extract at the trace level of larger bioactive 3-hydroxyquinaldic acid derivatives from which compounds 1–3 are biosynthetic precursors. Cytotoxicity tests confirmed the moderate and weak IC50 values of 15.6 and 51.5 µM for compounds 5 and 1, respectively

Desertomycin G, a New Antibiotic with Activity against <i>Mycobacterium tuberculosis</i> and Human Breast Tumor Cell Lines Produced by <i>Streptomyces althioticus</i> MSM3, Isolated from the Cantabrian Sea Intertidal Macroalgae <i>Ulva</i> sp.

The isolation and structural elucidation of a structurally new desertomycin, designated as desertomycin G (1), with strong antibiotic activity against several clinically relevant antibiotic resistant pathogens are described herein. This new natural product was obtained from cultures of the marine actinomycete Streptomyces althioticus MSM3, isolated from samples of the intertidal seaweed Ulva sp. collected in the Cantabrian Sea (Northeast Atlantic Ocean). Particularly interesting is its strong antibiotic activity against Mycobacterium tuberculosis clinical isolates, resistant to antibiotics in clinical use. To the best of our knowledge, this is the first report on a member of the desertomycin family displaying such activity. Additionally, desertomycin G shows strong antibiotic activities against other relevant Gram-positive clinical pathogens such as Corynebacterium urealyticum, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Enterococcus faecium, Enterococcus faecalis, and Clostridium perfringens. Desertomycin G also displays moderate antibiotic activity against relevant Gram-negative clinical pathogens such as Bacteroides fragilis, Haemophilus influenzae and Neisseria meningitidis. In addition, the compound affects viability of tumor cell lines, such as human breast adenocarcinoma (MCF-7) and colon carcinoma (DLD-1), but not normal mammary fibroblasts

Branimycins B and C, Antibiotics Produced by the Abyssal Actinobacterium Pseudonocardia carboxydivorans M-227.

Two new antibiotics, branimycins B (2) and C (3), were produced by fermentation of the abyssal actinobacterium Pseudonocardia carboxydivorans M-227, isolated from deep seawater of the Avilés submarine Canyon. Their structures were elucidated by HRMS and NMR analyses. These compounds exhibit antibacterial activities against a panel of Gram-positive bacteria, including Corynebacterium urealyticum, Clostridium perfringens, and Micrococcus luteus, and against the Gram-negative bacterium Neisseria meningitidis. Additionally, branimycin B displayed moderate antibacterial activity against other Gram-negative bacteria such as Bacteroides fragilis, Haemophilus influenzae, and Escherichia coli, and branimycin C against the Gram-positive Enterococcus faecalis and methicillin-sensitive and methicillin-resistant Staphylococcus aureus