Deciphering secondary metabolite potentials of halophilic marine-derived Aspergillus ruber

The halophilic marine-derived fungus Aspergillus ruber CBS 135680 was systematically investigated for its secondary metabolite potential through genome mining. A total of 36 biosynthetic gene clusters (BGCs) were identified, including four non-ribosomal peptide synthetase (NRPS) clusters, eight NRPS-like clusters, eight type I polyketide synthase (T1PKS) clusters, ten terpene clusters, four hybrid clusters, and two siderophore clusters. The largest NRPS cluster (AruBGC2, ~ 58 kb) encodes the siderophore synthase SidC, while AruBGC23 was linked to asperfuranone biosynthesis. Additional clusters were predicted to synthesize bioactive compounds such as cornexistin, TAN-1612, naphthopyrone, clavaric acid, squalestatin S1, asperlactone, and epipyriculol. These metabolites are associated with diverse biological activities, including anticancer, antibacterial, antifungal, nematocidal, and herbicidal properties. The discovery of canonical and noncanonical BGCs pinpoints the metabolic diversity of A. ruber and highlights potential as a promising source of natural products. This study provides the first comprehensive genome-wide assessment of secondary metabolism in A. ruber, offering valuable insights for future drug discovery and biotechnological applications.

The online version contains supplementary material available at 10.1007/s13205-026-04701-6.