Ribosomally synthesised and post-translationally modified peptides (RiPPs) from marine demosponges and their microsymbionts

Marine sponges are among the oldest animals to have emerged on Earth. They are metazoan holobionts that host diverse microbial symbionts, which constitute more than 40% of their biomass. Despite their morphological simplicity, sponges exhibit complex genetic architecture, unquestionably encoding ribosomally synthesised and post-translationally modified peptides (RiPPs) and proteins, essential for their biological functions. In addition to host-derived compounds, the associated microbiota also produce RiPPs, introducing further complexity in distinguishing the origin of these molecules. To date, marine sponge RiPPs research is confined to species within the class Demospongiae, with peptidomic, transcriptomic and genomic approaches employed for their discovery. This review provides a comprehensive account of current research on ribosomal peptides in marine sponges and associated microsymbionts, emphasising the need for expanded discovery efforts. Unravelling the genetic basis and biosynthetic pathways of these peptides will deepen our understanding of sponge biology and open new opportunities for peptide-based drug discovery.