Researchers in Germany have developed a new method to produce complex natural compounds like cannabinoids from amoebae – a development that they claim will help us produce more antibiotics and other natural compounds that are in short supply.
The produced polyketides include various antibiotics but also olivetolic acid, a precursor of the herbal active ingredient tetrahydrocannabinol (THC). The results were published in Nature Biotechnology.
Polyketides are natural products with a wide range of therapeutic applications. Among them are dietary supplements, various antibiotics such as erythromycin, and one of the key cannabinoid precursors: Olivetolic acid. It is needed for the synthesis of tetrahydrocannabinol (THC). The medical use of this psychoactive substance is being intensely researched, and it is already being used to provide relief for patients with neurological diseases and pain, among other things.
Bacteria such as Escherichia coli or the yeast Saccharomyces cerevisiae are already being used to create natural products, but they are not native producers of natural products and because of that a large number of genetic modifications is necessary to enable synthesis in these classic model organisms.
The research team is thus looking for alternatives. One promising candidate is the amoeba Dictyostelium discoideum, which already possesses numerous biosynthetic genes for the production of natural products such as polyketides. When scientists took a closer look at the genes, we noticed that some show a high similarity to plant biosynthetic genes.
To test how well D. discoideum is suited as a chassis organism for biotechnological production, the researchers first had the amoeba produce the food supplement resveratrol, also a polyketide. Afterwards they incorporated the plant enzyme that produces the THC precursor olivetolic acid into the amoeba’s genome. However, the addition of chemical precursors was still necessary to enable the synthesis.
To circumvent this, the researchers took advantage of the amoeba’s natural properties and combined the plant enzyme with an amoebic enzyme.