Metabologenomics-guided bioprospecting of blue amazon microbial resources toward drug discovery
摘要
The Brazilian marine territory known as the Blue Amazon represents a vast and underexplored reservoir of microbial diversity with potential for natural product discovery. Here, we applied an integrated metabologenomics approach to investigate two marine actinomycetes, Nocardiopsis dassonvillei CBMAI 3036 and Streptomyces sp. CBMAI 3038, previously reported to exhibit broad-spectrum antifungal activity. Whole-genome sequencing and phylogenomic analyses supported the assignment of CBMAI 3036 to Nocardiopsis dassonvillei and provided genomic evidence supporting CBMAI 3038 as a putative novel Streptomyces species. Genome mining identified numerous biosynthetic gene clusters, most displaying low similarity to known pathways, suggesting substantial unexplored biosynthetic potential. Untargeted UPLC–MS/MS metabolomics integrated with genomic data enabled the generation of putative associations between detected metabolites and candidate biosynthetic gene clusters. Integrated metabolomic and genomic analyses suggested that the previously reported antifungal activity of CBMAI 3036 may be associated with 1-hydroxyphenazine, whereas puromycin may contribute to the antifungal phenotype observed for CBMAI 3038. In silico analyses predicted favorable drug-likeness and ADMET profiles for 1-hydroxyphenazine, whereas puromycin showed a less favorable predicted toxicity profile, potentially limiting pharmaceutical applications while supporting future investigation in agricultural contexts. These findings highlight the Blue Amazon as a promising source of microbial and biosynthetic diversity and illustrate the usefulness of metabologenomics for generating hypotheses linking biosynthetic potential with putatively annotated metabolites.