Marine microorganisms have emerged as prolific sources of bioactive natural products, offering a large chemical diversity and a broad spectrum of biological activities. Over the past decade, significant progress has been made in discovering and characterizing these compounds, pushed by technological innovations in genomics, metabolomics, and bioinformatics. Furthermore, innovative isolation and cultivation approaches have improved the isolation of rare and difficult-to-culture marine microbes, leading to the identification of novel secondary metabolites. Advances in synthetic biology and metabolic engineering have further optimized natural product yields and the generation of novel compounds with improved bioactive properties. This review highlights key developments in the exploitation of marine bacteria, fungi, and microalgae for the discovery of novel natural products with potential applications in diverse fields, underscoring the immense potential of marine microorganisms in the growing Blue Economy sector.

With rising concerns about antimicrobial resistance, the identification of new lead compounds to target multidrug-resistant bacteria is essential. This study employed a fast miniaturized screening to simultaneously cultivate and evaluate about 300 marine strains for biosurfactant and antibacterial activities, leading to the selection of the deep-sea Bacillus halotolerans BCP32. The integration of tandem mass spectrometry molecular networking and bioassay-guided fractionation unveiled this strain as a prolific factory of surfactins and nobilamides. Particularly, 84 nobilamide congeners were identified in the bacterial exometabolome, 71 of them being novel metabolites. Among these, four major compounds were isolated, including the known TL-119 and nobilamide I, as well as the two new nobilamides T1 and S1. TL-119 and nobilamide S1 exhibited potent antibiotic activity against various multidrug-resistant Staphylococcus strains and other Gram-positive pathogens, including the foodborne pathogen Listeria monocytogenes. Finally, in silico analysis of Bacillus halotolerans BCP32 genome revealed nobilamide biosynthesis to be directed by a previously unknown heptamodular nonribosomal peptide synthetase.

Marine and pristine microbial ecosystems are often described as vast reservoirs of untapped biochemical diversity—but perhaps that description still understates their complexity. These environments, ranging from deep-sea trenches to glacial ice and isolated cave systems, impose constraints that seem, at first glance, incompatible with life. Yet it is precisely within these constraints that microorganisms appear to innovate most profoundly. This review attempts to bring together what is currently known—though not always consistently—about microbial diversity, biosynthetic potential, and bioactive compound production across such extreme habitats. Rather than focusing on isolated discoveries, the discussion moves across ecological gradients, linking environmental pressures with metabolic adaptation. Evidence suggests that marine systems tend to support broader biosynthetic capacity, while cryospheric and cave environments, although less diverse, often yield more specialized and structurally distinct metabolites. Particular attention is given to compounds such as kaempferol and complex polyketides, alongside the growing role of metagenomics in uncovering previously hidden biosynthetic gene clusters. At the same time, methodological limitations—especially the gap between genomic prediction and functional expression—remain difficult to ignore. Taken together, the literature points toward a field that is expanding rapidly, yet still uneven in its interpretive clarity. A more integrative approach—one that balances ecology, genomics, and chemistry—may be necessary to fully realize the biotechnological promise embedded within these microbial systems.