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

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.

Study at a glance

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.