A analysis staff on the Leibniz Institute for Pure Product Analysis and An infection Biology – Hans Knöll Institute (Leibniz-HKI) in Jena, Germany has developed a brand new technique to provide advanced pure merchandise in amoebae. These polyketides embrace numerous antibiotics but in addition olivetolic acid, a precursor of the natural lively ingredient tetrahydrocannabinol (THC). The outcomes have been printed in Nature Biotechnology.
Polyketides are pure merchandise with a variety of therapeutic functions. Amongst them are dietary dietary supplements, numerous antibiotics corresponding to erythromycin, and one of many key cannabinoid precursors: Olivetolic acid. It’s wanted for the synthesis of tetrahydrocannabinol (THC). The medical use of this psychoactive substance is being intensely researched, and it’s already getting used to supply aid for sufferers with neurological illnesses and ache, amongst different issues.
THC is a pure ingredient within the hashish plant. “Nevertheless, isolating THC in its pure kind from the abundance of drugs may be very advanced,” says Falk Hillmann, head of the junior analysis group “Evolution of Microbial Interactions” at Leibniz-HKI and coleader of the examine. Chemical synthesis of THC then again is pricey and the yield is low. That is why he and a staff are researching how such plant substances could be effectively produced biotechnologically.
“To date, micro organism corresponding to Escherichia coli or the yeast Saccharomyces cerevisiae are primarily used, however neither of them are native producers of pure merchandise,” explains Vito Valiante, head of the cooperating junior analysis group “Biobricks of Microbial Pure Product Syntheses” on the Leibniz-HKI. Accordingly, a lot of genetic modifications is important to allow synthesis in these traditional mannequin organisms. The analysis staff is thus in search of options. One promising candidate is the amoeba Dictyostelium discoideum, which already possesses quite a few biosynthetic genes for the manufacturing of pure merchandise corresponding to polyketides. “Taking a better have a look at the genes, we observed that some present a excessive similarity to plant biosynthetic genes,” stated first writer Christin Reimer, who’s engaged on the subject for her PhD.
To check how effectively D. discoideum is suited as a chassis organism for biotechnological manufacturing, the researchers first had the amoeba produce the meals complement resveratrol, additionally a polyketide. Afterwards they integrated the plant enzyme that produces the THC precursor olivetolic acid into the amoeba’s genome. Nevertheless, the addition of chemical precursors was nonetheless essential to allow the synthesis.
To avoid this, the researchers took benefit of the amoeba’s pure properties and mixed the plant enzyme with an amoebic enzyme. “The amoeba is ready to produce the required precursor, a hexane unit, immediately on web site,” Hillmann explains. Thus, the analysis staff succeeded in producing a practical inter-kingdom hybrid enzyme that produces olivetolic acid with none additional components.
By our analysis, we’ve got proven that the amoeba Dictyostelium can be utilized as a biotechnological manufacturing platform for polyketide-based pure merchandise.”
Christin Reimer, First Writer
The researchers already filed a patent for the method, and are striving to enhance it on an ongoing foundation. “Our subsequent aim is to insert the 2 enzymes which are nonetheless lacking so as to have the ability to produce the ultimate product THC within the amoebae,” Hillmann says.
Furthermore, a staff from the Bio Pilot Plant on the Leibniz-HKI was additionally concerned within the analysis. Johann Kufs, joint first writer of the examine alongside Reimer, is in control of creating and optimizing the synthesis course of for industrial utility.
The work was supported by the analysis group program of the state of Thuringia with funding from the European Social Fund in addition to by the German Federal Ministry of Schooling and Analysis (BMBF) – amongst others, as a part of the “GO-Bio preliminary” program.
Leibniz Institute for Pure Product Analysis and An infection Biology – Hans Knoell Institute
Reimer, C., et al. (2022) Engineering the amoeba Dictyostelium discoideum for biosynthesis of a cannabinoid precursor and different polyketides. Nature Biotechnology. doi.org/10.1038/s41587-021-01143-8.
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