Ibotenic Acid Biosynthesis in the Fly Agaric Is Initiated by Glutamate Hydroxylation.

Summary

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.

Study at a glance

Abstract

The fly agaric, Amanita muscaria, is widely known for its content of the psychoactive metabolites ibotenic acid and muscimol. However, their biosynthetic pathway and the respective enzymes are entirely unknown. 50 years ago, the biosynthesis was hypothesized to start with 3-hydroxyglutamate. Here, we build on this hypothesis by the identification and recombinant production of a glutamate hydroxylase from A. muscaria. The hydroxylase gene is surrounded by six further biosynthetic genes, which we link to the production of ibotenic acid and muscimol using recent genomic and transcriptomic data. Our results pinpoint the genetic basis for ibotenic acid formation and thus provide new insights into a decades-old question concerning a centuries-old drug.