For thousands of years, yeast helped us get drunk. During lockdown, many are discovering the wonders of yeast for sourdough baking projects. But synthetic biology researchers see more potential in yeast than just beer and bread. They have harnessed yeast’s powerful fermentation process to produce everything from egg proteins to pharmaceuticals. Now the Danish startup, Octarine, is giving yeast its first psychedelic awakening.
Octarine uses yeast fermentation to produce psilocybin and cannabinoids without the hassle of growing mushrooms or marijuana. They extracted the specific genes that create the drug from the plants and then inserted those genes into yeast DNA. By combining the modified yeast and a few simple sugars, Octarine produces a pure version of the drug while avoiding many of the limitations, costs and environmental sustainability issues of traditional plant cultivation or chemical synthesis.
“Psilocybe mushrooms are difficult to reproducibly cultivate on a large-scale,” co-found Nick Milne told Technology Networks. “They require a lot of infrastructure and maintenance and are prone to infection that can be very difficult to get rid of.”
Natural hosts are finicky. The plant cultivation requires substantial energy to power greenhouses and LED lighting systems, water resources for irrigation and a lot of labor. And even when grown perfectly, they produce very little of the desired substance, usually below 1 percent yield. Chemical synthesis is complicated, expensive and often starts with non-renewable chemicals and generates harmful by-products and emissions.
Octarine proposes that yeast fermentation produces psilocybin and cannabinoids at a much larger scale and with higher cost-efficiency. And because Octarine hopes to partner with major pharmaceutical companies, producing large amounts cheaply is key to success.
“We have been approached by several companies who are planning clinical trials but cannot get a stable supply of these molecules,” Nethaji Gallage, co-founder and CEO of Octarine wrote in an email. “Access to supply chain seems a key issue here.”
Until recently, pharmaceutical companies and medical professionals have avoided exploring psychedelic therapeutics. But with the legalization of marijuana, clinical studies on MDMA at universities like Johns Hopkins School of Medicine, and increased use of ketamine for depression, pharmaceutical corporations are starting to jump on the psychedelics bandwagon. In Denmark, psilocybin isn’t approved for medical use but Octarine has approval from the government to do research and development.
According to Octarine’s pitch, one of its main selling points to pharma companies is its technology can produce derivatives of cannabinoids and psilocybin not found in nature. By slightly tweaking the chemical compound, Octarine hopes to produce “superior” versions of these drugs. In some cases, the goal is a more bioavailable or more soluble version, but the pitch also mentions creating cannabinoids without psychoactive properties to appeal to the big drug companies.
“Many countries require medicinal products to be completely free of THC which is not feasible from plant-extraction,” Gallage wrote. “Biosynthetic cannabinoids can provide THC-free, 99 percent pure GMP cannabinoids to the medicinal market.”
However, new studies show the psychoactive property of psychedelic drugs might be key to mental health benefits. Creating drug variants without this mechanism could result in ineffective treatments. But Octarine believes there are many conditions where the compounds should act locally and not cross the Blood-Brain Barrier.
Of course creating novel drugs, especially ones with mind-altering properties, is always a tricky business, and Octraine will need to go through many clinical safety trials before entering the market. For now, we will have to stick to yeast’s first child for our mind-altering substances.