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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 \u00b0C) and extended incubation (9 days) maximized orsellinic acid accumulation. LC\u2013MS\/MS identified orsellinic acid as [M\u2013H]\u2013 at m\/z 167.0356, with the diagnostic fragment ion m\/z 122.8924, and quantified by HPLC\u2013DAD, achieving a concentration of 132 \u03bcg\/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\u2013plant metabolic interactions and highlights F. oxysporum as a sustainable biotechnological source of aromatic polyketides with potential applications in natural product chemistry and biocatalysis.<\/jats:p>","DOI":"10.1021\/acsomega.5c12178","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T22:13:27Z","timestamp":1784153607000},"page":"43107-43115","source":"Crossref","is-referenced-by-count":0,"title":["Orsellinic Acid\nfrom the Endophytic\n                    <i>Fusarium oxysporum<\/i>\n                    Drives Specialized Metabolism\nin\n                    <i>Peperomia obtusifolia<\/i>"],"prefix":"10.1021","volume":"11","author":[{"given":"Wellington Gomes","family":"de Lima","sequence":"first","affiliation":[{"name":"Universidade Estadual Paulista (UNESP) , , , ,","place":["Araraquara, Sa\u0303o Paulo, Brazil, 14800-900"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5428-768X","authenticated-orcid":true,"given":"Andreia de Arau\u0301jo","family":"Morandim-Giannetti","sequence":"additional","affiliation":[{"name":"Centro Universita\u0301rio da FEI , , , ,","place":["Sa\u0303o Bernardo do Campo, Sa\u0303o Paulo, Brazil, 09850-901"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joa\u0303o Luiz","family":"Bronzel Ju\u0301nior","sequence":"additional","affiliation":[{"name":"Universidade Estadual Paulista (UNESP) , , , ,","place":["Araraquara, Sa\u0303o Paulo, Brazil, 14800-900"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia Noeli\u0301","family":"Lo\u0301pez","sequence":"additional","affiliation":[{"name":"Universidad Nacional de Rosario - CONICET , , ,","place":["Rosario, Argentina, 2000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massuo Jorge","family":"Kato","sequence":"additional","affiliation":[{"name":"Universidade de Sa\u0303o Paulo (USP) , , , ,","place":["Sa\u0303o Paulo, Sa\u0303o Paulo, Brazil, 05508-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8434-5238","authenticated-orcid":true,"given":"Maysa","family":"Furlan","sequence":"additional","affiliation":[{"name":"Universidade Estadual Paulista (UNESP) , , , ,","place":["Araraquara, Sa\u0303o Paulo, Brazil, 14800-900"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"2026072810072546200_cit1","doi-asserted-by":"publisher","first-page":"3327","DOI":"10.1007\/s00253-019-09713-2","article-title":"Beneficial\nEffects of Endophytic Fungi Colonization on Plants","volume":"103","author":"Yan","year":"2019","journal-title":"Appl. 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