The fly agaric mushroom, Amanita muscaria, produces the psychoactive compounds ibotenic acid and muscimol, but their biosynthetic pathway and the enzymes involved were unknown. Fifty years ago, researchers hypothesized that the pathway begins with 3-hydroxyglutamate. This work identifies and recombinantly produces a glutamate hydroxylase from A. muscaria, supporting that hypothesis. The hydroxylase gene is flanked by six additional biosynthetic genes, which genomic and transcriptomic data link to ibotenic acid and muscimol production. These results pinpoint the genetic basis for ibotenic acid formation, resolving a decades-old question about a centuries-old drug.
The fly agaric mushroom produces psychoactive compounds ibotenic acid and muscimol. Fifty years ago, scientists proposed that their biosynthesis begins with 3-hydroxyglutamate. Researchers identified and recombinantly produced a glutamate hydroxylase enzyme from Amanita muscaria that supports this hypothesis. The gene for this enzyme is flanked by six other genes linked to ibotenic acid production based on recent genetic data. These findings offer new understanding of a long-standing question about a drug used for centuries.