by Friederike Gawlik, Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie – Hans-Knöll-Institut (Leibniz-HKI) Gold cap mushroom. Credit: Felix Blei/Leibniz-HKI An international research team has investigated the biosynthesis of psilocybin, the main ingredient of hallucinogenic mushrooms. They gained new insights into the structure and reaction mechanism of the enzyme PsiM. It plays a key role in the production of psilocybin. The results of the study were published in the journal Nature Communications .
The psychoactive substance psilocybin is the most important natural product of so-called "magic mushrooms" of the genus Psilocybe, which makes these mushrooms a popular drug. However, psilocybin has also become increasingly interesting in medicine in recent years for a number of mental illnesses. It has shown promising results in the treatment of depression, addiction and anxiety. Psilocybin is therefore already at an advanced stage of clinical testing as an active pharmaceutical ingredient .
Psilocybin is formed by fungi in complex biochemical processes from the amino acid L-tryptophan. The enzyme PsiM, a methyltransferase, plays an important role in this process. It catalyzes two methylation reactions in succession, the last two steps in the production of psilocybin.
"There are many methyl transfer reactions in nature," says Dirk Hoffmeister. He is Professor of Pharmaceutical Microbiology at Friedrich Schiller University Jena and heads an associated research group at the Leibniz Institute for Natural Product Research and Infection Biology—Hans Knöll Institute (Leibniz-HKI). "Here, we asked ourselves how exactly psilocybin production is accomplished." Two enzymes, one origin
To this end, a team from the Medical University of Innsbruck led by crystallographer Bernhard Rupp and the Jena researchers investigated the enzyme PsiM both biochemically and using X-ray crystal structure analysis. This method allows proteins to be visualized down to the atomic level , whereby several stages of the reaction could be depicted in ultra-high resolution.
Examination of the protein structure revealed astonishing similarities in structure between the fungal enzyme PsiM and enzymes that are normally responsible for the modification of RNA. Although there are also differences, the great structural similarity indicates that the fungal enzyme has evolved from a single methylating RNA methyltransferase.
Accordingly, it previously only had the ability to […]
New study sheds light on the structure and evolution of an enzyme in psychoactive fungi