Genomic landscape of biosynthetic gene clusters in Iranian extremophiles reveals prolific metabolite potential, prophage associations, and integrated defensive-metabolic islands

Abstract

The extreme and underexplored ecosystems of Iran represent a significant reservoir of microbial diversity with profound biosynthetic potential. To systematically investigate this resource, we employed a comprehensive genome mining approach on 16 bacterial isolates from hypersaline, desert, and petroleum-contaminated soils. Our analysis revealed an extraordinary density and complexity of biosynthetic gene clusters (BGCs), identifying 229 BGCs in total. A substantial majority (56.8%) showed no significant similarity to known clusters, underscoring the extensive novelty encoded within these extremophiles. Notably, we discovered highly intricate “trio” and “quartet” hybrid BGCs, which encode the machinery for three or four distinct classes of secondary metabolites, pushing the boundaries of known biosynthetic complexity. Parallel analysis identified six novel, high-quality prophages, largely uncharacterized in public databases. These prophages were found to carry a putative bacteriocin cluster (UviB) indicating a direct role in enhancing host fitness. Furthermore, we uncovered a dynamic co-evolutionary arms race, with bacterial genomes fortified by diverse defense systems, including abundant CRISPR-Cas arrays, and prophages encoding a repertoire of counter-defense anti-CRISPR proteins. Genomic architecture analysis revealed widespread co-localization of BGCs, prophages, and defense systems into functional genomic islands, suggesting a synergistic linkage between secondary metabolism and phage resistance. This study illuminates the remarkable biosynthetic and defensive landscape of Iranian extremophiles, highlighting them as a premier resource for discovering novel natural products and understanding virus-host evolutionary dynamics.