Cannabinoids from amoebae: New process for the production of active compounds

A research team at the Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute (Leibniz-HKI) in Jena, Germany has developed a new method to produce complex natural products in amoebae. These polyketides include various antibiotics but also olivetolic acid, a precursor of the herbal active ingredient tetrahydrocannabinol (THC).

THC is a natural ingredient in the cannabis plant. "However, isolating THC in its pure form from the abundance of substances is very complex," says Falk Hillmann, head of the junior research group "Evolution of Microbial Interactions" at Leibniz-HKI and coleader of the study. Chemical synthesis of THC on the other hand is expensive and the yield is low. That's why he and a team are researching how such plant substances can be efficiently produced biotechnologically.

The researchers took advantage of the amoeba's natural properties and combined the plant enzyme with an amoebic enzyme. "The amoeba is able to produce the required precursor, a hexane unit, directly on site," Hillmann explains. Thus, the research team succeeded in producing a functional inter-kingdom hybrid enzyme that produces olivetolic acid without any further additives.

"Through our research, we have shown that the amoeba Dictyostelium can be used as a biotechnological production platform for polyketide-based natural products," says Reimer. The researchers already filed a patent for the process, and are striving to improve it on an ongoing basis. "Our next goal is to insert the two enzymes that are still missing in order to be able to produce the final product THC in the amoebae," Hillmann says.