Magic Mushroom Compound Psilocybin Can Be Grown Using Yeast

Scientists from DTU Biosustain find that psilocybin, a potential drug for treating depression and other psychological conditions, can be produced in yeast. The Novo Nordisk Foundation Center for Biosustainability

Psilocybin, a potent compound that could help treat depression and other psychological conditions, is capable of being produced in yeast, presenting a commercially viable option for future pharmaceutical drugs that use the compound to treat psychological conditions.

Psilocybin is a key component of magic mushrooms found mainly in the Psilocybe mushroom genus, but psilocybin itself is not psychoactive. Rather, its derivative psilocin is what causes a hallucinogenic effect due to its similar structure to serotonin that binds to more than 15 serotonin-related receptors in the human brain.

At least 50 clinical trials have been completed or are currently underway to understand psilocybin’s efficacy as a treatment in the US alone, suggesting that the compound may be a good candidate for a number of mental health conditions, including managing addiction, anxiety in terminally ill patients, cluster headaches, and severe depression that doesn’t respond to other treatments.

“Although its notoriety originates from its psychotropic properties and popular use as a recreational drug, clinical trials have recently recognized psilocybin as a promising candidate for the treatment of various psychological and neurological afflictions,” write the researchers in the journal Metabolic Engineering.

After biosynthesis in Psilocybe mushroom species, psilocybin is typically administered by oral ingestion. Metabolic Engineering

Current studies rely on chemical synthesis, which is expensive and time-consuming, so finding a way to biotechnically produce psilocybin in a simple and cost-effective way is a key area of research. Some US cities, like Oakland and Denver, have decriminalized the use of magic mushrooms, but the trippy little fungal compound remains largely illegal in most US states and countries around the world. For clinical purposes, the content of psilocybin and psilocin in psychedelic mushrooms is too low to make extraction commercially viable and cultivating mushrooms is limited mainly to recreational users who have not generally streamlined their processes, resulting in different potencies that would be difficult to maintain at a large scale.

Researchers at DTU Biosustain found that Saccharomyces cerevisiae, a species of yeast that is common in winemaking, baking, and brewing, may serve as a host in growing psilocybin through a process known as “rational metabolic engineering.”

“While psilocybin is an interesting and pharmaceutically relevant molecule in its own right, one of the unique features of synthetic biology is the ability to “mix and match” enzymes to create new interesting molecules that aren't found in nature and are infeasible to produce by chemical synthesis,” write the authors.

The psilocybin molecule can be produced de novo in yeast, a biosynthetic method of production that simply needs sugar and other nutrients added, providing a much more economically feasible option for growing psilocybin in a laboratory setting

"It's infeasible and way too expensive to extract psilocybin from magic mushrooms and the best chemical synthesis methods require expensive and difficult to source starting substrates. Thus, there is a need to bring down the cost of production and to provide a more consistent supply chain," said study author Nick Milne, former Postdoc at DTU Biosustain and CSO and Co-founder of Octarine Bio, in a statement.

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