Global distribution of deep-sea natural products shows environmental and phylogenetic undersampling and potential for biodiscovery

Natural products from marine and terrestrial organisms provide an important resource for medicinal chemistry and drug discovery. Defined as occurring at depths greater than 200 m, most of the ocean, by area and volume, is comprised of deep-sea environments. These contrasting ecosystems exhibit a wide range of temperature, pressure, and environmental chemistry conditions that harbour high phylogenetic diversity. Here we analyse the global distribution of Marine Natural Products (MNPs) from deep-sea organisms, which reveals chronic undersampling of the deep ocean as a reservoir of structural novelty and diverse bioactivity. The sources of 2907 compounds and extracts, compiled from published records, show a sampling bias towards benthic and shallower deep-sea habitats, with relatively few from areas beyond national jurisdictions and a concentration of records along geomorphological features that have been the focus of marine scientific interest such as seamounts and hydrothermal vents. The phylogenetic distribution of deep-sea MNPs is dominated by non-metazoan sources (76% of records) and Ascomycota fungi in particular (55%). Polyketides are the most prevalent metabolites in deep-sea MNPs, and cytotoxic and antibacterial properties are the most commonly reported bioactivities. Our analyses highlight a need for systematic sampling and consistent data reporting to explore potential relationships between structural novelty, bioactivity, phylogeny and deep-sea environmental conditions, which could guide targeted biodiscovery in our planet's largest biome and enable better assessment of the benefits of protecting deep-sea biodiversity from human impacts.