TY - BOOK
T1 - High Times for Pathway Discovery
T2 - Phytocannabinoids - Origins, Biosynthesis and Synthetic Biology
AU - Gülck, Thies
PY - 2019
Y1 - 2019
N2 - Phytocannabinoids are a diverse group bio-active natural products found in flowering plants like Cannabis sativa, some liverworts and a few fungi. In humans, they interact with endocannabinoid receptors, ligand-gated ion channels and transcription factors making them potent sources for medicine and popular recreational drugs. In fact, phytocannabinoids are very effective in the treatment of neuropathic pain, chemotherapy-associated nausea, anxiety and AIDS-related loss of appetite. Unfortunately, only few phytocannabinoids are accessible in sufficient amounts that enable clinical trials or product development. My research addresses this issue through the advancement of biotechnological production methods such as heterologous biosynthesis. Heterologous biosynthesis means constructing a biosynthetic pathway in an organism other than the original producer and has the potential to make greater quantities of rare phytocannabinoids accessible. This requires in-depth knowledge of the involved enzymes, their encoding genes, regulation and subcellular localization. In this thesis, I present gene discovery of cannabigerolic acid synthase, the last unknown step in cannabinoid biosynthesis in Cannabis sativa. Furthermore, we use this gene to bioengineer the heterologous hosts Nicotiana benthamiana (tobacco) and Saccharomyces cerevisiae (yeast) towards production of cannabinoids. Our bioengineering work includes biotechnological glycosylation of cannabinoids in yeast. This achievement expands the chemical space within cannabinoids and increases the prospects for cannabinoids as drug leads.
AB - Phytocannabinoids are a diverse group bio-active natural products found in flowering plants like Cannabis sativa, some liverworts and a few fungi. In humans, they interact with endocannabinoid receptors, ligand-gated ion channels and transcription factors making them potent sources for medicine and popular recreational drugs. In fact, phytocannabinoids are very effective in the treatment of neuropathic pain, chemotherapy-associated nausea, anxiety and AIDS-related loss of appetite. Unfortunately, only few phytocannabinoids are accessible in sufficient amounts that enable clinical trials or product development. My research addresses this issue through the advancement of biotechnological production methods such as heterologous biosynthesis. Heterologous biosynthesis means constructing a biosynthetic pathway in an organism other than the original producer and has the potential to make greater quantities of rare phytocannabinoids accessible. This requires in-depth knowledge of the involved enzymes, their encoding genes, regulation and subcellular localization. In this thesis, I present gene discovery of cannabigerolic acid synthase, the last unknown step in cannabinoid biosynthesis in Cannabis sativa. Furthermore, we use this gene to bioengineer the heterologous hosts Nicotiana benthamiana (tobacco) and Saccharomyces cerevisiae (yeast) towards production of cannabinoids. Our bioengineering work includes biotechnological glycosylation of cannabinoids in yeast. This achievement expands the chemical space within cannabinoids and increases the prospects for cannabinoids as drug leads.
UR - https://soeg.kb.dk/permalink/45KBDK_KGL/fbp0ps/alma99123213869805763
M3 - Ph.D. thesis
BT - High Times for Pathway Discovery
PB - Department of Plant and Environmental Sciences, Faculty of Science, University of Copenhagen
ER -