Thies Gülck

Thies Gülck

PhD Student

Cannabis sativa accompanied humanity for millennia as a source for textile fiber, building material, food and medicine. The latter is due to the occurrence of phytocannabinoids in young leaves and glandular trichomes on the flower. Cannabis sp. produces more than 113 phytocannabinoids, but distinct cultivars exhibit different blends of phytocannabinoids. Thus, there are Cannabis cultivars that produce Δ9‑tetrahydrocannabinolic acid (THCA) (Marijuana cultivars) with the popular psychotropic effect and other cultivars that lack THCA (hemp cultivars). Phytocannabinoids in general have beneficial pharmaceutical effects and are used to treat pain, inflammation, anxiety, depression, nausea, sleeplessness Parkinson disease symptoms and more. The effects cannot be associated with individual compounds, but are a consequence of consuming the whole blend of phytocannabinoids and terpenoids.

Chemically, phytocannabinoids are terpenophenolic compounds that accumulate in storage cavities of glandular trichomes. Their biosynthetic pathway combines polyketide synthesis with the isoprenoid branch and is compartmentalized between plastids, cytosol and the storage cavity. In the polyketide branch, hexanoic acid is activated, chain elongated and cyclized by acyl-activating enzyme 1, tetraketide synthase and olivetolic acid cyclase yielding the polyketide derivative olivetolic acid (OA). OA is then prenylated with geranylpyrophosphate by an unknown prenyltransferase yielding cannabigerolic acid (CBGA). CBGA is the first real phytocannabinoid in the pathway and precursor to most other phytocannabinoids, including THCA.

We aim at elucidating the prenyltransferase step leading to CBGA, thereby establishing the full biosynthetic pathway. Secondarily, we engineer heterologous hosts (Nicotiana benthamiana, Saccharomyces cerevisiae) for the production of phytocannabinoids.

ID: 159692229