The biosynthetic pathway of the hallucinogen mescaline and its heterologous reconstruction
Molecular Plant June 3, 2024 Paula Berman, Luis Alejandro de Haro, Ana-Rita Cavaco et al. 15 citations
Mescaline, one of the earliest identified natural hallucinogens, has potential for psychotherapy, but its biosynthesis in the peyote cactus (Lophophora williamsii) was not fully understood. By combining genome and transcriptome sequencing with chemical profiling, enzymatic assays, and modeling, researchers identified four groups of enzymes responsible for the six catalytic steps in mescaline production, plus an N-methyltransferase that modifies all phenethylamine intermediates and likely modulates mescaline levels. The pathway was successfully reconstructed in tobacco plants and yeast cells, revealing challenges for complete heterologous production. This work enables sustainable production approaches and responsible use of mescaline.