Danish Scientists Modify Yeast to Create Psilocybin

Danish researchers have created a method to produce the hallucinogenic drug psilocybin that uses yeast instead of magic mushrooms. The new process could lead to mass production of the drug, which has shown promise as a treatment for depression and anxiety.

Nick Milne, a researcher with the Novo Nordisk Foundation Center for Biosustainability at the Technical University of Denmark (DTU Biosustain), said in a press release that the future wide-scale use of psilocybin is dependent on a cost-effective process to manufacture the compound in large quantities.

“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,” he said. “Thus, there is a need to bring down the cost of production and to provide a more consistent supply chain.”

The new method developed at DTU Biosustain makes it possible to create psilocybin de novo, meaning the chemical can be produced by the yeast using only sugar and nutrients without the addition of other compounds, which can be costly. The researchers noted that other methods to synthesize psilocybin have been created, although they have some drawbacks which make them expensive options for production.

New Process Improves on Other Methods

“Recently the company COMPASS Pathways developed and patented a new method for the chemical synthesis of psilocybin,” the team wrote in the study, “and while it improves on previous methods with an overall yield of 75%, it uses expensive 4-hydroxyindole as a starting substrate resulting in high production costs which may limit its application.”

Researchers at the University of Miami have modified a strain of the bacteria E. coli so that it produces psilocybin, but the process requires the addition of an enzyme that the bacteria is not able to produce by itself. The yeast used in the method from researchers at DTU Biosustain can produce the enzyme, however, making production more efficient.

“Since yeast and Psilocybe mushrooms are quite closely related species, this enzyme works very well in yeast, providing a much more cost-efficient alternative,” said Irina Borodina, a group leader at DTU Biosustain.

The team of researchers also noted that in addition to large-scale production of psilocybin, yeast could also be modified to produce similar compounds produced by magic mushrooms that are now difficult to synthesize.

“Our interest is not only to make kilogram scale production of psilocybin but to use the biological machinery to make new derivatives that aren’t available today,” Milne said. “Thus, it is very useful that we could not only demonstrate the production of psilocybin but also find many derivatives that could turn out to have important therapeutic relevance.”

Renewed interest in hallucinogens and the success of the cannabis legalization movement have led activists to call for the legalization of psilocybin mushrooms and other entheogenic plants and fungi. So far, decriminalization measures have succeeded in Denver, Oakland, and Santa Cruz, California.