{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T01:08:43Z","timestamp":1793149723859,"version":"4.5.0"},"reference-count":47,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,11,2]],"date-time":"2024-11-02T00:00:00Z","timestamp":1730505600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004895","name":"European Social Fund Plus","doi-asserted-by":"publisher","award":["2019FGR0079"],"award-info":[{"award-number":["2019FGR0079"]}],"id":[{"id":"10.13039\/501100004895","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004895","name":"European Social Fund Plus","doi-asserted-by":"publisher","award":["2022FGR0007"],"award-info":[{"award-number":["2022FGR0007"]}],"id":[{"id":"10.13039\/501100004895","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["239748522"],"award-info":[{"award-number":["239748522"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["enviromicro-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microbial Biotechnology"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The high therapeutic potential of psilocybin, a prodrug of the psychotropic psilocin, holds great promise for the treatment of mental disorders such as therapy\u2010refractory depression, alcohol use disorder and anorexia nervosa. Psilocybin has been designated a \u2018Breakthrough Therapy\u2019 by the US Food and Drug Administration, and therefore a sustainable production process must be established to meet future market demands. Here, we present the development of an in\u00a0vivo psilocybin production chassis based on repression of\n                    <jats:sc>l<\/jats:sc>\n                    \u2010tryptophan catabolism. We demonstrate the proof of principle in\n                    <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                    expressing the psilocybin biosynthetic genes. Deletion of the two aminotransferase genes\n                    <jats:italic>ARO8<\/jats:italic>\n                    \/\n                    <jats:italic>9<\/jats:italic>\n                    and the indoleamine 2,3\u2010dioxygenase gene\n                    <jats:italic>BNA2<\/jats:italic>\n                    yielded a fivefold increase of psilocybin titre. We transferred this knowledge to the filamentous fungus\n                    <jats:italic>Aspergillus nidulans<\/jats:italic>\n                    and identified functional\n                    <jats:italic>ARO8<\/jats:italic>\n                    \/\n                    <jats:italic>9<\/jats:italic>\n                    orthologs involved in fungal\n                    <jats:sc>l<\/jats:sc>\n                    \u2010tryptophan catabolism by genome mining and cross\u2010complementation. The double deletion mutant of\n                    <jats:italic>A. nidulans<\/jats:italic>\n                    resulted in a 10\u2010fold increased psilocybin production. Process optimization based on respiratory activity measurements led to a final psilocybin titre of 267\u2009mg\/L in batch cultures with a space\u2013time\u2010yield of 3.7\u2009mg\/L\/h. These results demonstrate the suitability of our engineered\n                    <jats:italic>A. nidulans<\/jats:italic>\n                    to serve as a production strain for psilocybin and other tryptamine\u2010derived pharmaceuticals.\n                  <\/jats:p>","DOI":"10.1111\/1751-7915.70039","type":"journal-article","created":{"date-parts":[[2024,11,2]],"date-time":"2024-11-02T08:39:18Z","timestamp":1730536758000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Optimized psilocybin production in tryptophan catabolism\u2010repressed fungi"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7361-495X","authenticated-orcid":false,"given":"Slavica","family":"Janevska","sequence":"first","affiliation":[{"name":"(Epi\u2010)Genetic Regulation of Fungal Virulence Leibniz Institute for Natural Product Research and Infection Biology\u2013Hans Kn\u00f6ll Institute  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6961-143X","authenticated-orcid":false,"given":"Sophie","family":"Weiser","sequence":"additional","affiliation":[{"name":"Bio Pilot Plant Leibniz Institute for Natural Product Research and Infection Biology\u2013Hans Kn\u00f6ll Institute  Jena Germany"},{"name":"Faculty of Biological Sciences Friedrich Schiller University  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Huang","sequence":"additional","affiliation":[{"name":"Biobricks of Microbial Natural Product Syntheses Leibniz Institute for Natural Product Research and Infection Biology\u2013Hans Kn\u00f6ll Institute  Jena Germany"},{"name":"Paleobiotechnology Leibniz Institute for Natural Product Research and Infection Biology\u2013Hans Kn\u00f6ll Institute  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Lin","sequence":"additional","affiliation":[{"name":"Biobricks of Microbial Natural Product Syntheses Leibniz Institute for Natural Product Research and Infection Biology\u2013Hans Kn\u00f6ll Institute  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6806-7063","authenticated-orcid":false,"given":"Sandra","family":"Hoefgen","sequence":"additional","affiliation":[{"name":"Biobricks of Microbial Natural Product Syntheses Leibniz Institute for Natural Product Research and Infection Biology\u2013Hans Kn\u00f6ll Institute  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"Joji\u0107","sequence":"additional","affiliation":[{"name":"Biobricks of Microbial Natural Product Syntheses Leibniz Institute for Natural Product Research and Infection Biology\u2013Hans Kn\u00f6ll Institute  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia E.","family":"Barber","sequence":"additional","affiliation":[{"name":"Fungal Informatics Friedrich Schiller University  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Sch\u00e4fer","sequence":"additional","affiliation":[{"name":"Pharmaceutical Microbiology Friedrich Schiller University  Jena Germany"},{"name":"Pharmaceutical Microbiology Leibniz Institute for Natural Product Research and Infection Biology\u2013Hans Kn\u00f6ll Institute  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janis","family":"Fricke","sequence":"additional","affiliation":[{"name":"Pharmaceutical Microbiology Friedrich Schiller University  Jena Germany"},{"name":"Pharmaceutical Microbiology Leibniz Institute for Natural Product Research and Infection Biology\u2013Hans Kn\u00f6ll Institute  Jena 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