Complete biosynthesis of psychedelic tryptamines from three kingdoms in plants
Paula Berman, Janka Höfer, Herschel Mehlman, Efrat Almekias-Siegl, Olga Khersonsky, Younghui Dong, Uwe Heinig, Liron Sulimani, Let Kho Hao, Shahar Cohen, Yoav Peleg, Sagit Meir, Ilana Rogachev, David Meiri, Sarel J. Fleishman, Asaph Aharoni
Science Advances April 1, 2026 DOI: 10.1126/sciadv.aeb3034 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Citations | 1 |
| Key findings | A versatile platform was established for concurrent biosynthesis and diversification of psychoactive indolethylamines in plants, enabling substantially more efficient production and creation of halogenated analogs with prospective therapeutic potential. |
Abstract
-dimethyltryptamine (DMT) biosynthetic pathway in hallucinogenic plant species traditionally used in shamanic rituals for spiritual healing. Leveraging the similarities in their chemical structures, we reconstructed in one plant assay the full biosynthetic pathways of five renowned natural psychedelics; psilocin and psilocybin found in mushrooms, DMT from plants, and bufotenin and 5-methoxy-DMT secreted by the Sonoran Desert toad. We further engineered halogenated analogs of these molecules, which do not naturally occur in plants and exhibit prospective therapeutic potential for psychiatric conditions. Blending catalytic functions across the tree of life, coupled with metabolic engineering guided by rational protein design of mutant enzymes, enabled substantially more efficient in planta production of the indolethylamine components. This work establishes a versatile platform for concurrent biosynthesis and diversification of psychoactive indolethylamines, paving the way for their production in plants.