Ibotenic acid biosynthesis in the fly agaric is initiated by glutamate hydroxylation

Abstract

The fly agaric, Amanita muscaria, is widely known for its content of the psychoactive metabolites ibotenic acid and muscimol. 50 years ago, their 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 corresponding gene is surrounded by six other genes, which we link to ibotenic acid production using recent genetic data. Our data provide new insights into a decades-old question concerning a centuries-old drug.