Active Ingredient in Magic Mushrooms Synthesized

For over a decade, marijuana has been touted as a wonder drug.  It is used to relieve pain and stress and treat symptoms of medical conditions as well as debilitating side effects from treatment.  With widespread acceptance and medicinal use of marijuana, researchers are now looking more seriously at other recreational drugs to determine if they have medicinal benefits as well.

Several papers released in 2016 documented a handful of therapeutic benefits associated with psilocybin, the active ingredient in psychedelic mushrooms. 

The “magic” of magic mushrooms comes from tryptamines, which are chemical derivatives of the amino acid L-tryptophan and structural relatives of the neurotransmitters serotonin and melatonin. 

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Until recently biosynthesis of psilocybin was not possible. In new research, published in the journal Angewandte Chemie, German scientists described a biosynthetic pathway for psilocybin and introduced a synthetic route that could form the basis of bioproduction.

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

In the first step of biosynthesis, an unusual 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 fairly easily synthesize psilocybin.

Given the increasing interest in psilocybin, this discovery could increase access to this recreational-turned-medicinal compound and help reduce depression and anxiety in cancer patients as well as potentially treat drug and alcohol dependence.

 

Psilocybe weilii image from WikiCommons

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