Comprehensive Genome Analysis of Two Bioactive Brevibacterium Strains Isolated from Marine Sponges from the Red Sea

Marine-derived Actinomycetota have emerged as promising sources of bioactive natural products, particularly filamentous actinomycetes (e.g., <i>Streptomyces</i>). However, members from non-filamentous genera have showed potential biotechnological importance. In this study, we performed a comprehensive genomic characterization of two bioactive <i>Brevibacterium</i> strains, <i>Brevibacterium luteolum (B. luteolum)</i> 26C and <i>Brevibacterium casei (B. casei)</i> 13A, isolated from two Red Sea sponges. Whole-genome sequencing and taxonomic analysis confirmed species-level identification, marking the first documented report of these species within the Red Sea ecosystem. The two strains displayed antimicrobial activity against <i>Staphylococcus aureus</i>, <i>Escherichia coli</i>, and <i>Candida albicans</i>. Additionally, functional annotation revealed multiple genomic islands (GIs) enriched with genes conferring heavy metal resistance, DNA repair enzymes, nutrient acquisition, and mobile genetic elements, highlighting potential evolutionary adaptations to the harsh physicochemical conditions of the Red Sea. Genome mining identified biosynthetic gene clusters, including those encoding ε-poly-L-lysine, tropodithietic acid, ectoine, and carotenoids. The comparative analysis of orthologous gene clusters from both strains and their counterparts from terrestrial ecosystems highlighted potential marine adaptive genetic mechanisms. This study highlights the biosynthetic potential of <i>B. luteolum</i> 26C and <i>B. casei</i> 13A and their ecological role as active competitors and potential defensive associates within the sponge microbiome.