New research shows that psilocybin—the psychoactive compound that puts the magic in magic mushrooms—can be made by bioengineered bacteria, highlighting a potential new way of mass-producing the valued chemical.
For the first time, scientists have demonstrated the possibility of coaxing a prokaryotic host, the bacterium Escherichia coli, into producing psilocybin. To do so, a team from Miami University in Ohio employed a technique known as metabolic engineering, in which biological cells are modified and cultivated to produce a specific chemical of interest. The new findings are published in Metabolic Engineering.
Psilocybin, aside from its recreational attributes, has shown its potential as a drug for treating various psychological conditions, including anxiety, addiction, depression, and PTSD. A number of clinical trials are currently underway in the United States to test the efficacy of this chemical to treat these conditions, including a phase 2 study for major depressive disorder.
Producing medical-grade psilocybin, however, is not easy or cheap. Mass production of psilocybin by farming magic mushrooms, such as crops of Psilocybe cubensis or Psilocybe semilanceata, involves “extensive real estate and time,” while synthetic chemical production remains cost prohibitive, according to a Miami University press release. Indeed, research from earlier this year estimated a cost of $2 per milligram for pharmaceutical-grade psilocybin (a 2011 study to treat anxiety with psilocybin used single dosages ranging between 10 to 30 mg, to give you an idea of the volumes required).
To come up with an alternative solution, Andrew Jones, an assistant professor in the department of chemical, paper, and biomedical engineering at Miami University, embarked upon an 18-month-long project to see if he and his students could coax a bacterium into producing psilocybin as a byproduct of its metabolism. In other words, the scientists were seeking to create bacteria that poops out psilocybin.
To start things off, the researchers created a new strain of E. coli bacteria, dubbed pPsilo16, in which the genes that encode for the production of psilocybin in magic mushrooms (specifically Psilocybe cubensis) were transferred to the bacteria.
“It’s similar to the way you make beer, through a fermentation process,” said Jones in the release. “We are effectively taking the technology that allows for scale and speed of production and applying it to our psilocybin producing E. coli.”
Alexandra Adams, lead author of the paper and an undergraduate chemical engineering major, said that once the DNA was transferred to the bacteria, “we saw [a tiny] peak emerge in our data. We knew we had done something huge,” she said in the press release.
The next step was to determine the most optimal conditions under which the mutated bacteria might produce psilocybin. To that end, the team experimented with different conditions to provide the most ideal conditions for fermentation, such as finding the best temperature and growth medium, the best nutrient mix for the bacteria, and so on. Eventually, the researchers settled on a protocol whereby the bacteria were able to produce concentrations amounting to 1.16 grams of psilocybin per liter.
“What’s exciting is the speed at which we were able to achieve our high production,” said Jones. “Over the course of this study we improved production from only a few milligrams per liter to over a gram per liter, a near 500-fold increase.”
As the authors conclude in the new study,
This work shows the first reported case of... psilocybin production using a prokaryotic host. Furthermore, this work highlights the power of tandem genetic and fermentation optimization to quickly identify key process parameters required to enable successful scale-up studies culminating in gram scale production of a high-value chemical product.
Looking ahead, the scientists would like to further improve the process, for example, by finding yet better ways of making the E. coli a producer of psilocybin and meeting production requirements that’ll inevitably be demanded by the pharmaceutical industry, should this technique advance to that point.
This is very promising research, but it’s important to remember that the sale and possession of psilocybin remains illegal in the U.S., though possession of it has been decriminalized in Denver, Colorado and Oakland, California.