Streptomycetes are widely distributed in the marine environment, although only a few studies on their associations to algae and coral ecosystems have been reported. Using a culture-dependent approach, we have isolated antibiotic-active Streptomyces species associated to diverse intertidal marine macroalgae (Phyllum Heterokontophyta, Rhodophyta, and Chlorophyta), from the central Cantabrian Sea. Two strains, with diverse antibiotic and cytotoxic activities, were found to inhabit these coastal environments, being widespread and persistent over a 3-year observation time frame. Based on 16S rRNA sequence analysis, the strains were identified as Streptomyces cyaneofuscatus M-27 and Streptomyces carnosus M-40. Similar isolates to these two strains were also associated to corals and other invertebrates from deep-sea coral reef ecosystem (Phyllum Cnidaria, Echinodermata, Arthropoda, Sipuncula, and Anelida) living up to 4.700-m depth in the submarine Avilés Canyon, thus revealing their barotolerant feature. These two strains were also found to colonize terrestrial lichens and have been repeatedly isolated from precipitations from tropospheric clouds. Compounds with antibiotic and cytotoxic activities produced by these strains were identified by high-performance liquid chromatography (HPLC) and database comparison. Antitumor compounds with antibacterial activities and members of the anthracycline family (daunomycin, cosmomycin B, galtamycin B), antifungals (maltophilins), anti-inflamatory molecules also with antituberculosis properties (lobophorins) were identified in this work. Many other compounds produced by the studied strains still remain unidentified, suggesting that Streptomyces associated to algae and coral ecosystems might represent an underexplored promising source for pharmaceutical drug discovery.

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.

Marine Actinobacteria are emerging as an unexplored source for natural product discovery. Eighty-seven deep-sea coral reef invertebrates were collected during an oceanographic expedition at the submarine Avilés Canyon (Asturias, Spain) in a range of 1500 to 4700 m depth. From these, 18 cultivable bioactive Actinobacteria were isolated, mainly from corals, phylum Cnidaria, and some specimens of phyla Echinodermata, Porifera, Annelida, Arthropoda, Mollusca and Sipuncula. As determined by 16S rRNA sequencing and phylogenetic analyses, all isolates belong to the phylum Actinobacteria, mainly to the Streptomyces genus and also to Micromonospora, Pseudonocardia and Myceligenerans. Production of bioactive compounds of pharmacological interest was investigated by high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) techniques and subsequent database comparison. Results reveal that deep-sea isolated Actinobacteria display a wide repertoire of secondary metabolite production with a high chemical diversity. Most identified products (both diffusible and volatiles) are known by their contrasted antibiotic or antitumor activities. Bioassays with ethyl acetate extracts from isolates displayed strong antibiotic activities against a panel of important resistant clinical pathogens, including Gram-positive and Gram-negative bacteria, as well as fungi, all of them isolated at two main hospitals (HUCA and Cabueñes) from the same geographical region. The identity of the active extracts components of these producing Actinobacteria is currently being investigated, given its potential for the discovery of pharmaceuticals and other products of biotechnological interest.

family of macrolide antibiotics known as nargenicins, 30 which exhibit antimicrobial activity mainly against Staph-31 ylococcus aureus. Nargenicins and branimycins have a tricyclic 32 structure with either a 9-or 10-membered lactone ring and 33 contain a unique ether bridge. In 1977, the first members of the 34 nargenicin family were isolated by Pfizer and Upjohn after the 35 aerobic fermentation of Nocardia argentinensis ATCC 31306. 36 This family of compounds and their antibacterial activity were 37 later patented, 1 and the structure of one of them, nargenicin 38 A1, was elucidated.2 Although it showed antibacterial activity in 39 vitro, this was restricted to Gram-positive bacteria, particularly 40 methicillin-resistant S. aureus (MRSA). It was also described 41 that nargenicin A1 induces cell differentiation and can be used, 42 therefore, as a possible treatment for neoplastic diseases. 43The first branimycin (1) was isolated in 1998 from the 44 Actinomycete GW 60/1571 and its structure determined by the 45

Members of the Streptomyces albidoflavus clade, identified by 16S rRNA sequencing and phylogenetic analyses, are widespread among predominant terrestrial lichens (Flavoparmelia caperata and Xanthoria parietina) and diverse intertidal and subtidal marine macroalgae, brown red and green (Phylum Heterokontophyta, Rhodophyta, and Chlorophyta) from the Cantabrian Cornice. In addition to these terrestrial and coastal temperate habitats, similar strains were also found to colonize deep-sea ecosystems and were isolated mainly from gorgonian and solitary corals and other invertebrates (Phylum Cnidaria, Annelida, Echinodermata, Arthropoda, and Porifera) living up to 4700-m depth and at a temperature of 2-4 °C in the submarine Avilés Canyon. Similar strains have been also repeatedly isolated from atmospheric precipitations (rain drops, snow, and hailstone) collected in the same area throughout a year observation time. These ubiquitous strains were found to be halotolerant, psychrotolerant, and barotolerant. Bioactive compounds with diverse antibiotic and cytotoxic activities produced by these strains were identified by high-performance liquid chromatography (HPLC) and database comparison. These include antibacterials (paulomycins A and B), antifungals (maltophilins), antifungals displaying also cytotoxic activities (antimycins and 6-epialteramides), and the antitumor compound fredericamycin. A hypothetical dispersion model is here proposed to explain the biogeographical distribution of S. albidoflavus strains in terrestrial, marine, and atmospheric environments.