{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:28:02Z","timestamp":1790184482607,"version":"4.1.0"},"reference-count":150,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Silver nanoparticles (AgNPs) synthesized via fungal-mediated biosynthesis have gained attention as eco-friendly alternatives to chemically produced nanomaterials, with broad biomedical potential. Fungi represent particularly attractive systems because their secretomes contain diverse biomolecules, including enzymes, proteins, polysaccharides, and secondary metabolites, capable of reducing silver ions and stabilizing the resulting nanoparticles. Despite extensive investigation, the molecular mechanisms underlying fungal-mediated AgNP formation remain poorly defined. This review critically examines the key biomolecular drivers involved in this process, with emphasis on nitrate reductases, oxidoreductases, extracellular proteins, polysaccharides, and secondary metabolites as potential reducing and capping agents. Proposed mechanisms, including nitrate reductase-dependent, superoxide-mediated, and metabolite-driven pathways, are evaluated. The influence of process parameters such as silver nitrate concentration, incubation time, culture medium composition, pH, temperature, and fungal species on nanoparticle yield, size, and stability is also assessed. Analysis of the current literature highlights significant knowledge gaps, including limited application of proteomic and metabolomic approaches, a lack of causal mechanistic studies, and insufficient standardization of experimental protocols. Overall, evidence indicates that fungal AgNP biosynthesis is governed by complex interactions among multiple biomolecular classes rather than a single universal mechanism, underscoring priorities for improving reproducibility, scalability, and mechanistic understanding.<\/jats:p>","DOI":"10.3390\/ijms27136029","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:43:14Z","timestamp":1783345394000},"page":"6029","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Who Reduces Silver? A Critical Review of the Biomolecular Drivers of Fungal-Mediated Silver Nanoparticle Biosynthesis"],"prefix":"10.3390","volume":"27","author":[{"given":"Mislav","family":"Vorkapi\u0107","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Osijek, Ulica Cara Hadrijana 8\/A, 31 000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3127-3442","authenticated-orcid":false,"given":"Nikolina","family":"Filipovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Osijek, Ulica Cara Hadrijana 8\/A, 31 000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5090-0435","authenticated-orcid":false,"given":"Anamarija","family":"Stankovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Osijek, Ulica Cara Hadrijana 8\/A, 31 000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Ami\u0107","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Osijek, Ulica Cara Hadrijana 8\/A, 31 000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"38516","DOI":"10.1038\/s41598-025-00595-1","article-title":"Green synthesis and characterization of silver nanoparticles from Gilaburu under varying temperature and pH, with antimicrobial activity and spectral inconsistencies","volume":"15","author":"Ektiren","year":"2025","journal-title":"Sci. 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