Single-celled organisms: a cannabinoid factory?

February 16, 2022
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In general, they do not have a particularly good reputation: Many amoebae contain bacteria that can cause diseases in humans. A group of researchers from the Leibniz Institute for Natural Product Research and Infection Biology in Jena has now managed to pull off a trick – they have made the amoeba Dictyostelium discoideum produce a precursor of the active ingredient in cannabis, tetrahydrocannabinol (THC).   

Amoebae are single-celled organisms and are capable of producing numerous natural substances. In the case of the genus Dictyostelium discoideum – a slime mould – these are various polyketides that can be used for a whole range of therapeutic applications. These include the cannabinoid precursor olivetolic acid. The principle of action of the single-celled organisms in this respect: they join together to form larger structures that can act like a multicellular organism. 

Reactivation of slime mould enzymes 

In the course of their research, the Jena working group first found that the slime moulds produced either resveratrol (a secondary plant substance to which, among other things, an anti-inflammatory effect is attributed) or olivetolic acid, depending on the experimental set-up. The catch: the synthesis only works if a special chemical additive is present in the nutrient medium. Beyond that, the amount produced is marginal.   

In the next step, the research team developed a way to combine the slime mould enzymes with an enzyme from the hemp plant. A hybrid construct is created that is inserted into the genetic material of Dictyostelium discoideum. As a result, the amoeba directly produces the required precursor – olivetolic acid is thus produced without further additives.   

Dictyostelium discoideum acts as a production platform 

In the next step, the research team wants to produce the end product THC directly in the amoebae by introducing two more missing enzymes into the single-celled organism. A patent for the biotechnological extraction of the plant substances has already been applied for. It is particularly promising because the chemical extraction of THC in its pure form is very time-consuming, expensive and associated with low yields. Microbes, on the other hand, can be cultivated en masse and thus theoretically produce large quantities of THC in a short time. The production is not dependent on the growth of a plant or the climatic conditions. 

Original source:   

Reimer C, Kufs JE, Rautschek J, Regestein L, Valiante V, Hillmann F. Engineering the amoeba Dictyostelium discoideum for biosynthesis of a cannabinoid precursor and other polyketides. Nat Biotechnol. 2022 Jan 6. doi: 10.1038/s41587-021-01143-8. Epub ahead of print. PMID: 34992245.  

 

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