Antibacterial metabolites from a heterobranchia-associated bacteria and their prey from Bali, Indonesia

Marine-associated bacteria serve as a significant source of bioactive natural products for drug discovery efforts. The microbial symbionts of heterobranchs and their prey represent a promising source of bioactive compounds with potential applications as pharmaceutical agents. This study aimed to evaluate the diversity of associated microbes of heterobranchs and their prey that were obtained from one of marine biodiversity hotspots. The next step involved employing in vitro antibacterial screening of the organic extracts of the bacterial strains to determine the most potent ones. Microbiome study revealed that <i>Hypselodoris roo</i> had the most diverse microbiome, with Proteobacteria and Firmicutes bacterial taxa predominating among six heterobranchia samples. A total of 46 bacterial strains and 243 actinobacterial strains have been isolated from six nudibranchs and their prey sources. Next, <i>Ruegeria</i> sp., a symbiont from the sponge prey, exhibited the most promising antibacterial. Subsequent chromatographic purification revealed the presence of three known cyclic dipeptides: cyclo(Leu-Pro) (<b>1</b>), cyclo(Phe-Pro) (<b>2</b>), and cyclo(phenylalanine-4‑hydroxy-proline) (<b>3</b>), along with an indazole <b>4</b> in the extract of <i>Ruegeria</i> sp. All the metabolites have never been reported from this symbiont bacteria associated to the organisms examined in this study.