Soil microorganisms mediate several biological processes through the secretion of natural products synthesized in specialized metabolic pathways, yet functional characterization in ecological contexts remains challenging. Using culture-independent metagenomic analyses of microbial DNA derived directly from soil samples, we examined the potential of biosynthetic gene clusters (BGCs) from six bacterial communities distributed along an altitudinal gradient of the Andes Mountains in the Atacama Desert. We mined 38 metagenome-assembled genomes (MAGs) and identified 168 BGCs. Results indicated that most predicted BGCs were classified as non-ribosomal-peptides (NRP), post-translational modified peptides (RiPP), and terpenes, which were mainly identified in genomes of species from Acidobacteriota and Proteobacteria phyla. Based on BGC composition according to types of core biosynthetic genes, six clusters of MAGs were observed, three of them with predominance for a single phylum, of which two also showed specificity to a single sampling site. Comparative analyses of accessory genes in BGCs showed associations between membrane transporters and other protein domains involved in specialized metabolism with classes of biosynthetic cores, such as resistance-nodulation-cell division (RND) multidrug efflux pumps with RiPPs and the iron-dependent transporter TonB with terpenes. Our findings increase knowledge regarding the biosynthetic potential of uncultured bacteria inhabiting pristine locations from one of the oldest and driest nonpolar deserts on Earth.IMPORTANCEMuch of what we know about specialized metabolites in the Atacama Desert, including Andean ecosystems, comes from isolated microorganisms intended for drug development and natural product discovery. To complement research on the metabolic potential of microbes in extreme environments, comparative analyses on functional annotations of biosynthetic gene clusters (BGCs) from uncultivated bacterial genomes were carried out. Results indicated that in general, BGCs encode for structurally unique metabolites and that metagenome-assembled genomes did not show an obvious relationship between the composition of their core biosynthetic potential and taxonomy or geographic distribution. Nevertheless, some members of Acidobacteriota showed a phylogenetic relationship with specific metabolic traits and a few members of Proteobacteria and Desulfobacterota exhibited niche adaptations. Our results emphasize that studying specialized metabolism in environmental samples may significantly contribute to the elucidation of structures, activities, and ecological roles of microbial molecules.
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