A „Magic Mushroom“ Multi‐Product Sesquiterpene Synthase
ChemBioChem – August 24, 2023
Source: OpenAlex
Summary
Beyond their known psychotropic tryptamines, "magic mushrooms" produce diverse natural products. A single sesquiterpene synthase enzyme, CubA, from *Psilocybe cubensis* was characterized. Its biochemistry was explored by expressing it in *Escherichia coli*. This terpenoid-producing enzyme synthesizes compounds like cubebol, β-copaene, and δ-cadinene, also found in the mushroom. This work, relevant to Psychedelics and Drug Studies, reveals the broader metabolic biology and plant biochemistry of *Psilocybe* species. It advances our understanding of natural product biosynthesis and chemistry, including potential roles for these compounds beyond alkaloids, impacting chemical synthesis.
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.