Peyote, a cactus native to the Chihuahuan desert, produces the psychoactive compound mescaline, but how the plant makes it has been unknown for over 120 years. Using gene discovery guided by transcriptomics and homology, researchers identified a near-complete biosynthetic pathway from the amino acid l-tyrosine to mescaline. They found a cytochrome P450 enzyme that converts l-tyrosine to l-DOPA, a decarboxylase that produces dopamine, and four specific O-methyltransferases that modify phenethylamines. Biochemical assays with recombinant enzymes and engineered yeast confirmed substrate specificity. An N-methyltransferase was also identified that may contribute to the early steps of tetrahydroisoquinoline alkaloid biosynthesis in peyote.
The specialized metabolite profile in Psychotria viridis leaves, a plant used in ayahuasca preparation, varies with growing conditions and seasonality. Flavonoids were the main compounds differentiating seasonal samples. Energy-related pathways—ascorbate and aldarate metabolism, pentose and glucuronate interconversions, and the citrate cycle—showed significant seasonal variation. Flavonoid, flavone, and flavonol biosynthesis differed between plants grown in full sunlight versus shade, suggesting a response to oxidative stress. DMT concentrations did not significantly change across conditions.