Magic enzymes in 'magic' mushrooms analyzed

Enzymatic synthesis of psilocybin, the ingredient of magic mushrooms

August 25, 2017

Science Daily/Wiley

Little fungi pack a punch: "Magic mushrooms" of the Psilocybe species produce psychoactive compounds that alter perception when ingested. Recently, the effects on the neuronal system caused by their ingredient psilocybin have attracted the interest of pharmacologists. German scientists have now identified four of the enzymes responsible for the biosynthesis of psilocybin. In the journal Angewandte Chemie, they describe the biosynthetic pathway and introduce a synthetic route that could form the basis of biotechnological production.

For centuries, Central American cultures considered Psilocybe mushrooms to be divine and used them for spiritual purposes. More recently, they have been called magic mushrooms and used for their hallucinogenic effects. These mushroom drugs may soon also be in use as pharmaceuticals that treat the existential anxiety of advanced-stage cancer patients, depression, and nicotine addiction. Their effects stem from tryptamines, which are chemical derivatives of the amino acid L-tryptophan and structural relatives of the neurotransmitters serotonin and melatonin. Among these, psilocybin is the primary chemical mushroom component. Psilocybin is an inactive precursor that is rapidly activated when consumed: splitting off a phosphate group results in the actual active ingredient, psilocin.

Although the structure of psilocybin has been known for about 60 years, it has not been possible to decode the enzymatic basis of its biosynthesis. Researchers working with Dirk Hoffmeister at the Friedrich Schiller University of Jena have now figured this out. They have identified the four enzymes that transform the amino acidy L-tryptophan into psilocybin. Using genetic technology, the researchers were able to produce the enzymes in bacterial and mould fungi cultures and characterize them.

Based on this knowledge, they were also able to clarify the biosynthetic production route, which is different than previously supposed. In the first step of the biosynthesis, an unsusual type of tryptophan decarboxylase splits the carboxyl group off of the amino acid L-tryptophan. A monooxygenase then introduces an alcohol group, to which a kinase subsequently adds a phosphate group. Finally, a methyl transferase adds two methyl groups stepwise to the amino group.

Starting with 4-hydroxy-L-tryptophan and using three of the four fungal enzymes, the scientists were able to enzymatically synthesize psilocybin by a simple method in a combined reaction. Given the pharmaceutical industry's renewed interest in psilocybin, these results may lay the foundation for its biotechnological production.

https://www.sciencedaily.com/releases/2017/08/170825103955.htm

Evolutionary relationships among species of 'magic' mushrooms shed light on fungi

August 6, 2013

Science Daily/Canadian Science Publishing (NRC Research Press)

"Magic" mushrooms are well known for their hallucinogenic properties. Until now, less has been known about their evolutionary development and how they should be classified in the fungal Tree of Life. New research helps uncover the evolutionary past of a fascinating fungi that has wide recreational use and is currently under investigation for a variety of medicinal applications.

In the 19th century, the discovery of hallucinogenic mushrooms prompted research into the mushrooms' taxonomy, biochemistry, and historical usage. Gastón Guzmán, a world authority on the genus Psilocybe, began studying its taxonomy in the 1950s. In 1983, these studies culminated in a monograph, which is currently being updated as a team of researchers from the University of Guadalajara and the University of Tennessee collaborate with Guzmán to produce a hypothesis on how these mushrooms evolved. Some of their latest research is now published in the journal Botany.

Using new molecular and computational techniques, the team has produced the first multi-gene evaluation of the evolutionary development of Psilocybe, which constitutes a major step in classifying and naming "magic" mushrooms. Earlier work showed that species of Psilocybe did not commonly descend from a single ancestor. As a result, the hallucinogenic species (the genus Psilocybe) were typically separated from their non-hallucinogenic relatives (the genus Deconica). But this new work now places the two separate monophyletic -- meaning developed from a single ancestor -- groups into different families. Within Psilocybe (family Hymenogastraceae) and Deconica (family Strophariaceae s.str), the authors have discovered several strong infrageneric relationships.

According to the authors, their analysis of various morphological traits of the mushrooms suggests that these typically weren't acquired through a most recent common ancestor and must have evolved independently or undergone several evolutionary losses, probably for ecological reasons. Nevertheless, species of Psilocybe are united to some degree because they have the psychedelic compound psilocybin and other secondary metabolites, or products of metabolism. The authors say that former Psilocybe species that lack these secondary metabolites could also be found in Deconica.

https://www.sciencedaily.com/releases/2013/08/130806132852.htm