02 October 2019

Psilocybin from a bioreactor

E. coli has been turned into a psychedelic factory

"Vesti"

When they talk about magic mushrooms, they primarily mean mushrooms of the genus Psilocybe. They look unremarkable – ordinary toadstools, but inside there is a substance that has a special effect.

We are talking about a psychedelic called psilocybin. First of all, it is known as a hallucination stimulant, but now it is increasingly being tested as a potential treatment for mental disorders, including various addictions, major depression and post-traumatic stress disorder.

By the way, the other day it became known about the opening of the Center for Psychedelic Research and Consciousness in Baltimore on the basis of Johns Hopkins University. Huge funds are being poured into the new center and a great future is being predicted for it.

However, the experiment in question was organized in another institution, at the University of Miami – this is a private secular university in the USA. Actually, the scientists were faced with the task of organizing mass production of psilocybin without growing mushrooms. There is not so much of the right substance in mushrooms, and it does not seem cost-effective to create mushroom farms.

Researchers quite expectedly turned to bacteria for help, since they have long established themselves as mini-factories for the production of certain substances. For example, some medications, including the hormone insulin, are already being produced with the help of genetically engineered bacteria.

In this case, the researchers manipulated the metabolism of Escherichia coli (aka E. coli, aka E. coli). E. coli is famous among bioengineers for being prolific, well studied, and a large universal set of genetic tools is applicable to it.

"We simply took the DNA of the Psilocybe fungus and placed it in E.coli," says study co–author Andrew Jones, professor of chemical and biological engineering (in a press release Miami researchers discover process to sustainably produce psilocybin - a drug candidate that could help treat depression - VM). As a result of the modifications, the microbe cells began to produce psilocybin.

psilocybin.jpg

From left to right: Miami University Associate Professor Andrew Jones and his group, students Lexie Adams, Tom Wei, Nick Kaplan, Alexis Enacopol, Chantal Monnier & John Brinton – VM.

The team of scientists initially created several strains of psychedelic E. coli, but only one was recognized as a promising candidate – it was called pPsilo16. It provided the highest concentration of psilocybin with the minimum amount of undesirable by-products.

The researchers then worked on optimization by conducting a series of experiments to determine the best fermentation conditions. We have identified the best culture medium, the best temperature and the best nutrient mixture for the production of psilocybin.

Finally, the team was able to bring the production of psychedelic to large bioreactors, adjusting the process so as to eventually obtain a concentration of 1.16 g of psilocybin per liter. Thus, E. coli pPsilo16 produces more psilocybin than any of the known organisms modified with the help of the "magic mushroom" DNA.

"What's amazing is the speed at which we were able to achieve high performance," Jones shared. Indeed, in just a year and a half of work, the researchers were able to increase the synthesis of psilocybin by 500 times.

According to the scientists, they presented convincing evidence that psilocybin can be synthesized on an industrial scale necessary for the production of psychopharmacological drugs.

Article by Adams et al. In vivo production of psilocybin in E. coli is published in the journal Metabolic Engineering – VM.

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