{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T16:25:09Z","timestamp":1787329509862,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32470046"],"award-info":[{"award-number":["32470046"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Fungal secondary metabolites serve as crucial virulence effectors; however, the potential of their biosynthetic pathways as antifungal targets remains inadequately comprehended. In this study, we put forward a novel antifungal strategy that targets the conserved global secondary metabolic pathway in pathogenic fungi. Through genome mining, phylogenetic analysis, and structural modeling, we identified invariant residues in phosphopantetheinyl transferases (PPTases), which are essential for secondary metabolism, and revealed them as pan\u2010fungal targets. High\u2010throughput screening indicated that the FDA\u2010approved tepotinib and eltrombopag bind to PPTases to interfere with mycotoxin biosynthesis, thereby reducing the fungal burden and alleviating lung inflammation in a mouse model of pulmonary aspergillosis. These compounds exhibited broad\u2010spectrum activity against common pathogens, including\n                    <jats:italic>Aspergillus fumigatus<\/jats:italic>\n                    ,\n                    <jats:italic>Mucor circinelloides<\/jats:italic>\n                    ,\n                    <jats:italic>Aspergillus flavus<\/jats:italic>\n                    ,\n                    <jats:italic>Fusarium oxysporum<\/jats:italic>\n                    ,\n                    <jats:italic>Cryptococcus neoformans<\/jats:italic>\n                    , and\n                    <jats:italic>Cryptococcus gattii<\/jats:italic>\n                    . Notably, both drug candidates demonstrated synergistic effects with amphotericin B, reducing its half\u2010maximal inhibitory concentration by 7.4\u2010 and 2.6\u2010fold, respectively. This research provides a metabolic targeting framework and paves new paths for the rational design of broad\u2010spectrum antifungals and combination therapies.\n                  <\/jats:p>","DOI":"10.1002\/advs.77354","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T15:19:18Z","timestamp":1787325558000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Repurposing FDA\u2010Approved Drugs to Inhibit Fungal PPTases for Broad\u2010Spectrum Synergy"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5087-8290","authenticated-orcid":false,"given":"Zili","family":"Song","sequence":"first","affiliation":[{"name":"State Key Laboratory of Microbial Diversity and Innovative Utilization Institute of Microbiology Chinese Academy of Sciences  Beijing China"},{"name":"Medical School University of Chinese Academy of Sciences  Beijing 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