Comprehensive analysis of 42 psilocybin-producing fungal strains reveals metabolite diversity and species-specific clusters
Abstract Psilocybin-producing fungi have garnered attention due to accumulating evidence regarding the therapeutic potential of their principal component psilocybin. This diverse group of fungi harbors a wealth of less-studied metabolites, however, thus far most research has addressed them as a cohe...
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Nature Portfolio
2025-04-01
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| Online Access: | https://doi.org/10.1038/s41598-025-97710-z |
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| author | Jonathan Cohen Liron Sulimani Shiri Procaccia Yaniv Lerenthal Looz Milay Ido Taran Anna Shapira David Meiri |
| author_facet | Jonathan Cohen Liron Sulimani Shiri Procaccia Yaniv Lerenthal Looz Milay Ido Taran Anna Shapira David Meiri |
| author_sort | Jonathan Cohen |
| collection | DOAJ |
| description | Abstract Psilocybin-producing fungi have garnered attention due to accumulating evidence regarding the therapeutic potential of their principal component psilocybin. This diverse group of fungi harbors a wealth of less-studied metabolites, however, thus far most research has addressed them as a cohesive group. By optimizing an approach for extraction and analysis, we examined the metabolomes of 42 distinct fungi strains and show that the breadth and diversity of metabolites within and between 9 species. We integrated and validated the reproducible and reliable extraction of fruiting bodies followed by chromatographic separation, quantification and identification of their known and yet to be identified secondary metabolites. The optimal extraction of fruiting bodies for high yield of indole alkaloids was achieved using a 1:20 tissue:solvent ratio, 25:75 H2O:MeOH (pH = 9), for 1.5 h, followed by the quantification of 8 tryptophan-derived indolamines by HPLC–DAD and the identification of putative metabolite hydroxypsilocybin by HPLC–MS/MS. The metabolomic analysis revealed the diversity of metabolites within and between species. Finally, we developed and present a method that mimics the in vivo process of dephosphorylation that occurs upon ingestion for in vitro setups. Overall, our study summarizes a standardized approach for both in vitro and in vivo studies involving psilocybin-producing fungi, showcasing the unique metabolome of each strain and the rich diversity of these fungi, encompassing promising pharmaceutical potential. |
| format | Article |
| id | doaj-art-16c13d33f5314d9dab782df6e36faa03 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-16c13d33f5314d9dab782df6e36faa032025-08-20T03:13:57ZengNature PortfolioScientific Reports2045-23222025-04-0115111310.1038/s41598-025-97710-zComprehensive analysis of 42 psilocybin-producing fungal strains reveals metabolite diversity and species-specific clustersJonathan Cohen0Liron Sulimani1Shiri Procaccia2Yaniv Lerenthal3Looz Milay4Ido Taran5Anna Shapira6David Meiri7Laboratory of Cancer Biology and Natural Drug Discovery, Faculty of Biology, Technion-Israel Institute of TechnologyThe Kleifeld Laboratory, Faculty of Biology, Technion-Israel Institute of TechnologyLaboratory of Cancer Biology and Natural Drug Discovery, Faculty of Biology, Technion-Israel Institute of TechnologyPsygaBioPsygaBioPsygaBioLaboratory of Cancer Biology and Natural Drug Discovery, Faculty of Biology, Technion-Israel Institute of TechnologyLaboratory of Cancer Biology and Natural Drug Discovery, Faculty of Biology, Technion-Israel Institute of TechnologyAbstract Psilocybin-producing fungi have garnered attention due to accumulating evidence regarding the therapeutic potential of their principal component psilocybin. This diverse group of fungi harbors a wealth of less-studied metabolites, however, thus far most research has addressed them as a cohesive group. By optimizing an approach for extraction and analysis, we examined the metabolomes of 42 distinct fungi strains and show that the breadth and diversity of metabolites within and between 9 species. We integrated and validated the reproducible and reliable extraction of fruiting bodies followed by chromatographic separation, quantification and identification of their known and yet to be identified secondary metabolites. The optimal extraction of fruiting bodies for high yield of indole alkaloids was achieved using a 1:20 tissue:solvent ratio, 25:75 H2O:MeOH (pH = 9), for 1.5 h, followed by the quantification of 8 tryptophan-derived indolamines by HPLC–DAD and the identification of putative metabolite hydroxypsilocybin by HPLC–MS/MS. The metabolomic analysis revealed the diversity of metabolites within and between species. Finally, we developed and present a method that mimics the in vivo process of dephosphorylation that occurs upon ingestion for in vitro setups. Overall, our study summarizes a standardized approach for both in vitro and in vivo studies involving psilocybin-producing fungi, showcasing the unique metabolome of each strain and the rich diversity of these fungi, encompassing promising pharmaceutical potential.https://doi.org/10.1038/s41598-025-97710-zPsilocybin-producing fungiPsilocybinFungal extractionLiquid chromatographyFungal metabolomeDephosphorylation |
| spellingShingle | Jonathan Cohen Liron Sulimani Shiri Procaccia Yaniv Lerenthal Looz Milay Ido Taran Anna Shapira David Meiri Comprehensive analysis of 42 psilocybin-producing fungal strains reveals metabolite diversity and species-specific clusters Scientific Reports Psilocybin-producing fungi Psilocybin Fungal extraction Liquid chromatography Fungal metabolome Dephosphorylation |
| title | Comprehensive analysis of 42 psilocybin-producing fungal strains reveals metabolite diversity and species-specific clusters |
| title_full | Comprehensive analysis of 42 psilocybin-producing fungal strains reveals metabolite diversity and species-specific clusters |
| title_fullStr | Comprehensive analysis of 42 psilocybin-producing fungal strains reveals metabolite diversity and species-specific clusters |
| title_full_unstemmed | Comprehensive analysis of 42 psilocybin-producing fungal strains reveals metabolite diversity and species-specific clusters |
| title_short | Comprehensive analysis of 42 psilocybin-producing fungal strains reveals metabolite diversity and species-specific clusters |
| title_sort | comprehensive analysis of 42 psilocybin producing fungal strains reveals metabolite diversity and species specific clusters |
| topic | Psilocybin-producing fungi Psilocybin Fungal extraction Liquid chromatography Fungal metabolome Dephosphorylation |
| url | https://doi.org/10.1038/s41598-025-97710-z |
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