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There is a limited number of antifungals available and resistance to all of them has been reported. The development of novel antifungals is complex, as eukaryotic organisms have very few selective drug targets that distinguish them from the infected plant, human, or animal host. Yeasts produce different compounds with antifungal activity, ranging from small molecules such as iron chelators, biosurfactants, and volatile organic compounds, to proteins like myocins and hydrolytic enzymes. Those could be further developed into new antifungals; however, there is a scarcity of fundamental knowledge on their chemical structure, their mode of action, their biosynthesis, and its regulation. Given the opportunities that yeasts display as industrial hosts and the synthetic biology tools available, a deeper understanding of these molecular aspects could enable a wider range of yet underexplored applications for the producer yeast and their molecules, from biocontrol to food preservation and human health. To facilitate this exploration, we here consolidate current molecular knowledge on these compounds, suggest readily available methodologies to screen for different molecule classes in natural yeast isolates and discuss how they could be further studied and engineered towards their eventual application.<\/jats:p>","DOI":"10.1093\/femsyr\/foaf068","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T13:06:47Z","timestamp":1763557607000},"source":"Crossref","is-referenced-by-count":5,"title":["Yeast-secreted compounds with antifungal activity\u2014screening, genetic parts, biosynthetic pathways, and regulation"],"prefix":"10.1093","volume":"25","author":[{"given":"Alicia","family":"Maci\u00e1\u00a0Valero","sequence":"first","affiliation":[{"name":"Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen , 9747 AG Groningen ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Lu","sequence":"additional","affiliation":[{"name":"Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen , 9747 AG Groningen ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3092-578X","authenticated-orcid":false,"given":"Sonja","family":"Billerbeck","sequence":"additional","affiliation":[{"name":"Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen , 9747 AG Groningen ,","place":["the Netherlands"]},{"name":"Imperial College London Department of Bioengineering, , South Kensington Campus , London SW7 2AZ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,11,19]]},"reference":[{"key":"2025121909273804700_bib1","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1016\/j.sjbs.2020.10.058","article-title":"Production and potential biotechnological applications of microbial surfactants: an overview","volume":"28","author":"Adetunji","year":"2021","journal-title":"Saud J Biol Sci"},{"key":"2025121909273804700_bib2","volume-title":"Plant Pathology","author":"Agrios","year":"2005","edition":"5th edn."},{"key":"2025121909273804700_bib3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/jof7090768","article-title":"The siderophore transporters sit1 and sit2 are essential for utilization of ferrichrome-, ferrioxamine-and coprogen-type siderophores in Aspergillus fumigatus","volume":"7","author":"Aguiar","year":"2021","journal-title":"J Fungi"},{"key":"2025121909273804700_bib4","doi-asserted-by":"publisher","first-page":"2283","DOI":"10.1021\/bi00762a012","article-title":"Protonated amino acid precursor studies on rhodotorulic acid biosynthesis in deuterium oxide media","volume":"11","author":"Akers","year":"1972","journal-title":"Biochemistry"},{"key":"2025121909273804700_bib191","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2017\/2605382","article-title":"Production, characterization, and antimicrobial activity of mycocin produced by Debaryomyces hansenii DSMZ70238","volume":"2017","author":"Al-Qaysi","year":"2017","journal-title":"Int J Microbiol"},{"key":"2025121909273804700_bib5","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1016\/j.jmb.2012.11.033","article-title":"The atomic structure of the virally encoded antifungal protein, KP6","volume":"425","author":"Allen","year":"2013","journal-title":"J Mol Biol"},{"key":"2025121909273804700_bib6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fmicb.2019.00214","article-title":"The still underestimated problem of fungal diseases worldwide","volume":"10","author":"Almeida","year":"2019","journal-title":"Front Microbiol"},{"key":"2025121909273804700_bib7","doi-asserted-by":"publisher","first-page":"e0143641","DOI":"10.1371\/journal.pone.0143641","article-title":"Exploring the Saccharomyces cerevisiae volatile metabolome: indigenous versus commercial strains","volume":"10","author":"Alves","year":"2015","journal-title":"PLoS One"},{"key":"2025121909273804700_bib8","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1007\/978-1-4419-5979-9_18","article-title":"Biosurfactants from yeasts: characteristics, production and application","volume":"672","author":"Amaral","year":"2010","journal-title":"Adv Exp Med Biol"},{"key":"2025121909273804700_bib9","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1017\/S0953756203008220","article-title":"Rhodotorulic acid production by Rhodotorula mucilaginosa","volume":"107","author":"Andersen","year":"2003","journal-title":"Mycol Res"},{"key":"2025121909273804700_bib10","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/0014-5793(72)80635-5","article-title":"Biosynthesis of sideramines in fungi. 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