Diverse biosynthetic pathways in Arctic hydrothermal biofilms

Biosynthetic gene clusters (BGCs) which encode diverse secondary metabolites are ubiquitous across microbiomes and support critical ecological functions. They also serve as attractive targets for new drug discovery. Here we combined genome-resolved metagenomics with long-read Nanopore RNA sequencing, yielding 1016 bacterial and 124 archaeal medium-to-high quality MAGs from previously unchartered microbial communities in Arctic hydrothermal vent biofilms. We identified 2965 BGCs from 870 metagenome-assembled genomes (MAGs) comprising a distinctive and rich diversity of BGCs, with ribosomally synthesized and post-translationally modified peptides (RiPPs) predominating across all samples. RiPPs and non-ribosomal peptide synthetases (NRPs), also known to encode metabolites with antimicrobial potential, are represented among the most expressed transcripts. Terpenes, though less expressed, contribute to microbial signaling and defense. Notably, we identify hydrogen cyanide (HCN) synthesis pathways in archaeal genomes, challenging the view that cyanogenesis is restricted to bacteria and eukaryotes. Our findings demonstrate that microbial adaptation to extreme environments favors RiPP-based biosynthesis and that HCN may play a role in archaeal ecological interactions. Moreover, microbial communities in Arctic hydrothermal vent biofilms provide a rich reservoir of unique bioactive compounds, with implications for drug discovery.