Metabologenomic assessment of biosynthetic capabilities in the genus Salinibacterium: untapped bioactive chemistry produced by marine strain AL4.1 isolated in the Chilean Patagonia

Background: Antimicrobial resistance (AMR) represents one of the most critical global public health challenges. Increasing evidence suggests that rare actinomycetes can harbor novel biosynthetic diversity to produce antimicrobial compounds. This work explores the capabilities for the biosynthesis of antimicrobial natural products of Salinibacterium sp. AL4.1, in contrast with those of Salinibacterium sp. VpJ6, through a comparative metabologenomic approach. Results: An initial bioactivity screening performed with strain AL4.1 informed a second round of comparative bioactivity tests using both strains AL4.1 and VpJ6, which revealed antimicrobial bioactivity of crude extracts from strain AL4.1 against Staphylococcus aureus . LC-MS/MS was performed on the tested samples, allowing for chemical dereplication, structural annotation and classification, as well as identification of bioactivity-associated features. This revealed the presence of potential structural analogs of known bioactive compounds such as platyphyllenone and phloretin, for which bacterial production had not been reported to date, as well as other potentially novel alkaloids and peptides. The genomes of both strains were sequenced and mined for their biosynthetic capabilities and further compared to those of other Salinibacterium strains with available genomic data. Phylogenomic studies suggested that both strains AL4.1 and VpJ6 could represent potentially new species. A mainly phylogeny-dependent distribution of biosynthetic gene clusters (BGCs) was observed, emphasizing the presence of a widely distributed type III PKS BGC, which could be linked to the bioactive compounds. Conclusions: These results suggest that Salinibacterium sp. AL4.1 can produce novel bioactive natural products, and that the genus Salinibacterium holds relevant and underexplored biosynthetic potential.