Scientists Unlock Magic Mushrooms’ Mysterious Chemical Compound

A new study has uncovered the enzymatic pathways that allow ‘shrooms to make psilocybin

Alan Rockefeller/Wikimedia Commons

Magic mushrooms make us feel real groovy thanks to a chemical compound called psilocybin, which, once it is converted by the body into the molecule psilocin, has a hallucinogenic effect. Scientists have known the chemical structure of psilocybin since the late 1950s, but the biochemcial pathways that allow ‘shrooms to make the compound have remained obscure—until now.

As Stephen K. Ritter reports for Chemical & Engineering News, researchers at Friedrich Schiller University in Jena, Germany have isolated four enzymes that magic mushrooms use to make psilocybin. The team was also able to create the first enzymatic synthesis of psilocybin—a potentially ground-breaking step towards commercializing the compound, which in recent years has been shown to be helpful in treating anxiety, depression and other psychological disorders.

For the study, which was published in the German journal Angewandte Chemie, researchers sequenced the genomes of two different mushrooms species: Psilocybe cubensis and Psilocybe cyanescens. As Mike McRae points out for Science Alert, a 1968 paper investigating psilocybin’s biosynthesis theorized that the process began with a molecule of tryptophan, an essential amino acid. The new study found that tryptophan was indeed the initial building block, but that the order of events proposed by the earlier paper was otherwise incorrect. Gizmodo’s George Dvorksy explains how the process works:

"It starts with a special kind of tryptophan molecule, with an extra oxygen and hydrogen stuck on, like an anglerfish with a big head and a tail and an extra piece hanging off like the headlight. An enzyme the researchers named PsiD first strips a carbon dioxide molecule off of the tail. Then, an enzyme they called PsiK phosphorylates it, meaning it replaces the headlight’s oxygen with a special setup of phosphorus with some oxygen attached. A final enzyme, called PsiM, works to replace two hydrogen atoms on the tail with methyl groups, or carbon atoms with three hydrogens attached."

Once they figured out how mushrooms make psilocybin, researchers genetically modified E. coli bacteria to synthetically produce the enzymes involved in the compound’s production, Sam Lemonick of Forbes reports. 

“The new work lays the foundation for developing a fermentation process for production of this powerful psychedelic fungal drug, which has a fascinating history and pharmacology," Courtney Aldrich, a medicinal chemist at the University of Minnesota who was not involved in the research, tells Ritter of Chemical & Engineering News.

Although psilocybin was long disregarded by the scientific community—it is, after all, an illicit drug—recent studies have suggested that the compound can be helpful in treating a host of psychological conditions. Psilocybin has been shown to reduce anxiety in patients with life-threatening cancers, alleviate symptoms of depression, and even help people kick nicotine habits.

Psilocybin is still a controlled substance in many places, so it will likely be a long time before it is accepted by the community as a medical treatment. But the new study is a promising first step in unlocking the healing powers of funky fungi.

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