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

Angew Chem Int Ed Engl. 2020 Jul 20;59(30):12432-12435. doi: 10.1002/anie.202001870. Epub 2020 Jun 5.


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.

Keywords: biosynthesis; enzyme catalysis; fly agaric; hydroxylation; ibotenic acid.

MeSH terms

  • Amanita / metabolism*
  • Glutamic Acid / metabolism*
  • Hydroxylation
  • Ibotenic Acid / biosynthesis*
  • Muscimol / metabolism


  • Ibotenic Acid
  • Muscimol
  • Glutamic Acid