Gems From the Caves: Genomic Insights Into the Biosynthetic Potential of Antimicrobial-Producing Bacteria Associated With Tropical Cave-Dwelling Sponges.

Submarine caves are promising frontiers for novel biomolecules active against multidrug-resistant bacteria. These habitats harbour rich communities of marine sponges, whose microbiomes produce diverse bioactive metabolites. The present study investigates the potential of bacteria isolated from cave-dwelling marine sponges of the class Demospongiae of a tropical archipelago for the production of antimicrobial substances and reveals their biosynthetic diversity by genomic analyses. Ten out of the 89 antimicrobial-producing strains showed inhibitory activity against Gram-positive and Gram-negative bacteria, encompassing strains with multidrug-resistant phenotypes. Biosynthetic gene clusters (BGCs) encoding antimicrobial-active metabolites were predicted in these sponge-derived pseudomonads. Most BGCs exhibited low similarity (< 80%) with known clusters, indicating potential for novel metabolite discovery. Comparative genomics across Pseudomonadaceae genomes revealed both species-specific and shared BGCs, including conserved clusters encoding for koreenceine and bokeelamides biosynthesis. Some cryptic BGCs encoded antimicrobial peptides (AMPs) together with proteins associated with maturation, regulation, immunity and export, suggesting roles in observed bioactivity. Altogether, this work expands the genomic and biosynthetic landscape of sponge-associated Pseudomonadaceae and uncovers promising gene clusters for the biotechnological exploration of novel antimicrobials.