Microbial communities associated with marine sponges from diverse geographic locations harbor biosynthetic novelty.

Marine sponges are a prolific source of biologically active small molecules, many of which originate from sponge-associated bacteria. Identifying the producing bacteria is a key step in developing sustainable routes for the production of these metabolites. To facilitate the required computational analyses, we developed MetaSing, a reproducible singularity-based pipeline for assembly, identification of high-quality metagenome-assembled genomes (MAGs), and analysis of biosynthetic gene clusters (BGCs) from metagenomic short-read data. We applied this pipeline to metagenomic sequencing data from 16 marine sponges collected from New Zealand, Tonga, and the Mediterranean Sea. This analysis yielded 643 MAGs representing 510 species. Of the 2,670 BGCs identified across all samples, 70.8% were linked to a MAG. Comparison of BGCs to those identified from previously sequenced bacteria revealed high biosynthetic novelty in variety of underexplored phyla, including Poribacteria, Acidobacteriota, and Dadabacteria. Alongside the observation that each sample contains unique biosynthetic potential, this holds great promise for natural product discovery and for furthering the understanding of different sponge holobionts.IMPORTANCEDiscovery of new chemical compounds such as natural products is a crucial endeavor to combat the increasing resistance to antibiotics and other drugs. This manuscript demonstrates that microbial communities associated with marine sponges investigated in this work encode the potential to produce novel chemistry. Lesser studied bacterial taxa that are often difficult to cultivate are particularly rich in potential.