Orsellinic Acid from the Endophytic Fusarium oxysporum Drives Specialized Metabolism in Peperomia obtusifolia.

The metabolic cooperation between plants and their endophytic fungi represents a promising frontier in the biosynthesis of natural products. This study elucidates the contribution of the endophytic fungus Fusarium oxysporum Po18 to the production of aromatic polyketides that drive specialized metabolism in Peperomia obtusifolia. Cultivation parameters for F. oxysporum were optimized using a Central Composite Rotatable Design (CCRD), revealing that mild temperatures (28 °C) and extended incubation (9 days) maximized orsellinic acid accumulation. LC-MS/MS identified orsellinic acid as [M-H]- at m/z 167.0356, with the diagnostic fragment ion m/z 122.8924, and quantified by HPLC-DAD, achieving a concentration of 132 μg/mL under optimized conditions. Comparative metabolomic analysis and molecular networking (GNPS) revealed related fungal metabolites, including lecanoric acid, 6-methylsalicylic acid, and citrinin, all derived from the fungal polyketide synthase (PKS) pathway. These metabolites are proposed to act as biosynthetic precursors for chroman and benzopyran derivatives previously reported in P. obtusifolia. The results provide the first experimental evidence of a biosynthetic partnership between Fusarium and Peperomia, in which the endophyte may supply aromatic scaffolds that could subsequently undergo downstream modifications in the host plant. This study expands the understanding of fungal-plant metabolic interactions and highlights F. oxysporum as a sustainable biotechnological source of aromatic polyketides with potential applications in natural product chemistry and biocatalysis.