Taxonomic Diversity and Metabolic and Pharmacological Profiles of Marine-Derived Actinomycetes from the Lisbon and Setúbal Coast, Portugal

This study explores the taxonomic diversity, metabolic profile, and bioactivity of marine-derived actinomycetes isolated from sediments collected off the coast of Lisbon and Setúbal Peninsula, Portugal. The combined use of two sediment pre-treatments (heat shock and dry overnight) and four growth media with varying nutrient concentrations revealed that formulations 10% A1 and SWA were most effective for recovering diverse actinomycetes, including rare <i>Actinomadura</i>, resulting in a total of 142 cultivable strains closely related to 47 phylogenetic distinct species dominated by <i>Streptomyces</i> and <i>Micromonospora</i>. Antimicrobial screening against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA, COL) and <i>Escherichia coli</i> (K12) identified 22 bioactive strains, with strain PTS-083 exhibiting the strongest activity against MRSA (MIC = 1.95 µg/mL) and a 98.30% 16S rRNA gene identity to <i>S. chumphonensis</i>, highlighting it as a strong candidate for further metabolite and genomic studies. Cytotoxicity assays against HCT-116 human colorectal adenocarcinoma cells revealed eight bioactive strains with potent anticancer activity for extracts from strains related to <i>S. sundarbansensis</i>, <i>S. violaceorubidus</i>, and <i>S. aculeolatus</i> (IC₅₀ < 0.005-5.08 µg/mL). Untargeted LC-MS/MS metabolomic analysis uncovered a wide array of secondary metabolites, including macrolides, siderophores, fatty acids, and cyclic peptides. Comparative analyses with other Portuguese coastal studies revealed both shared and distinctive metabolomic profiles, emphasizing the importance of exhaustive sampling, even at nearby locations, since localized environmental conditions can influence metabolic diversity and are crucial for uncovering unique metabolites with potential biotechnological value. These findings highlight Portugal's coastal sediments as a rich and underexplored source of novel actinomycetes and bioactive compounds with promising pharmaceutical applications.