Multi-Omic Assessment of Microbial Communities and Their Polyketide Biosynthetic Potential Across Abyssal Sediments.

Microbially-derived polyketides include some of today's most valuable medicines, yet their discovery has focused on a narrow subset of Earth's microbial biodiversity. Although understudied biomes such as marine sediments have been targeted, these efforts have focused on samples collected from shallow waters. In contrast, abyssal marine sediments (4000-6000 m), which comprise > 80% of the ocean floor, remain poorly explored. This leaves foundational gaps in our understanding of deep-sea microbial diversity and its relationship to biosynthetic potential. Here, we used culture-independent approaches to characterise microbial taxonomic and biosynthetic diversity in abyssal sediments collected from three geochemically distinct plains along an 880 km transect. Sediment communities varied in both taxonomic (16S rRNA gene) and biosynthetic (ketosynthase domain) composition across sites and relative to nearshore sediments, suggesting they harbour unique opportunities for natural product discovery. Ketosynthase phylogenies revealed abyssal clades that diverged from experimentally characterised polyketide synthase pathways, further supporting biosynthetic novelty. Metagenome-assembled genomes linked unique ketosynthase domains to the poorly studied phylum Gemmatimonadota. Sediment metabolomes provided evidence of chemical novelty, with < 10% of the features detected matching previously reported spectra. These baseline findings indicate that abyssal sediments represent reservoirs of unexplored polyketide biosynthetic diversity.