A „Magic Mushroom“ Multi‐Product Sesquiterpene Synthase

Psilocybe 'magic mushrooms' are well known for their psychotropic tryptamines, but the diversity of other specialized metabolites, especially terpenoids, has remained unclear. CubA, the single clade II sesquiterpene synthase from Psilocybe cubensis, was produced in Escherichia coli and characterized in vitro, with additional in vivo assays in Aspergillus niger. GC-MS analyses showed CubA functions as a multi-product synthase, producing cubebol, β-copaene, δ-cadinene, and germacrene D as major products depending on reaction conditions. Analysis of mature P. cubensis mushrooms detected β-copaene and δ-cadinene. Closely related enzymes are encoded in genomes of various Psilocybe species, providing insight into the metabolic capacity of the entire genus.

Study at a glance

Abstract

Abstract Psilocybe “magic mushrooms” are chemically well understood for their psychotropic tryptamines. However, the diversity of their other specialized metabolites, in particular terpenoids, has largely remained an open question. Yet, knowledge on the natural product background is critical to understand if other compounds modulate the psychotropic pharmacological effects. CubA, the single clade II sesquiterpene synthase of P. cubensis , was heterologously produced in Escherichia coli and characterized in vitro , complemented by in vivo product formation assays in Aspergillus niger as a heterologous host. Extensive GC‐MS analyses proved a function as multi‐product synthase and, depending on the reaction conditions, cubebol, β‐copaene, δ‐cadinene, and germacrene D were detected as the major products of CubA. In addition, mature P. cubensis carpophores were analysed chromatographically which led to the detection of β‐copaene and δ‐cadinene. Enzymes closely related to CubA are encoded in the genomes of various Psilocybe species. Therefore, our results provide insight into the metabolic capacity of the entire genus.