{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:12:02Z","timestamp":1788786722476,"version":"build-2803163510"},"reference-count":33,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32372617"],"award-info":[{"award-number":["32372617"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32070507"],"award-info":[{"award-number":["32070507"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32070495"],"award-info":[{"award-number":["32070495"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32372617"],"award-info":[{"award-number":["32372617"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["32070507"],"award-info":[{"award-number":["32070507"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["32070495"],"award-info":[{"award-number":["32070495"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Fungi","JoF"],"abstract":"<jats:p>The prophenoloxidase (PPO) melanization cascade is a cornerstone of insect humoral immunity against fungal pathogens, yet its direct fungicidal mechanism remains undefined, and strategies to safely manipulate this pathway for biological control are lacking. Here, we demonstrate that infection of Drosophila by the entomopathogenic fungus Beauveria bassiana elicits a surge in phenoloxidase (PO) activity directly triggered by the fungal cell wall component \u03b2-1,3-Glucan. This activated PO generates reactive oxygen species (ROS) that are essential for restricting fungal proliferation, thereby establishing a mechanistic link between cascade activation and fungicidal outcome. Critically, we uncover that N-acetylcysteine (NAC), a safe, low-cost pharmaceutical in global clinical use, acts as a potent direct inhibitor of PO enzymatic activity, neutralizing the melanization-driven ROS burst. NAC-mediated inhibition significantly accelerates B. bassiana virulence and host mortality in vivo. Our work defines a new molecular function for NAC as a melanization inhibitor and reveals a safe, translatable strategy to suppress host immune defenses, offering a promising approach to enhance the efficacy of fungal biopesticides for sustainable pest control worldwide.<\/jats:p>","DOI":"10.3390\/jof12090670","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T12:12:25Z","timestamp":1788783145000},"page":"670","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["N-Acetylcysteine Attacks Phenoloxidase to Inhibit Insect Melanization and Boost Fungal Virulence"],"prefix":"10.3390","volume":"12","author":[{"given":"Yingyu","family":"Tang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering, New World Institute of Biotechnology, East China University of Science and Technology, Shanghai 200237, China"},{"name":"University of Chinese Academy of Sciences, Beijing 101408, China"},{"name":"CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200036, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9872-2590","authenticated-orcid":false,"given":"Yuyang","family":"Lian","sequence":"additional","affiliation":[{"name":"University of Chinese Academy of Sciences, Beijing 101408, China"},{"name":"CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200036, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Shirong","family":"Li","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Research and Utilization of Resource Plants on the Loess Plateau, College of Life Sciences, Yan\u2019an University, Yan\u2019an 716000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Erjun","family":"Ling","sequence":"additional","affiliation":[{"name":"CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200036, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Dongzhi","family":"Wei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering, New World Institute of Biotechnology, East China University of Science and Technology, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Wuren","family":"Huang","sequence":"additional","affiliation":[{"name":"CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200036, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"ref_1","unstructured":"Yamanaka, N., and Atkinson, P.W. 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