Engineering Nicotiana benthamiana for production of active cannabinoid synthases via secretory pathway optimization
Year: 2024
Type: article
Abstract: The production of cannabinoid compounds like Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabichromene (CBC) is rapidly increasing due to their pharmaceutical potential. However, the low yield of minor cannabinoids, legal restrictions, and high purification costs from Cannabis sativa necessitate a biotechnological approach. Cannabinoids can be produced in yeast, insect cells, and plants via heterologous expression of tetrahydrocannabinol acid synthase (THCAS). Both THCAS and cannabidiolic acid synthase (CBDAS) use cannabigerolic acid (CBGA) as a substrate. This study transiently expressed recombinant THCAS and CBDAS in Nicotiana benthamiana leaves, demonstrating efficient expression in the secretory pathway with heterologous signal peptides. Both proteins were secreted to the apoplast and were heavily glycosylated with Golgi-processed N-glycans. Glycosylation is crucial for CBDAS protein folding or stability. In vitro assays confirmed that plant-made recombinant CBDAS and THCAS are enzymatically active.
Source: Biotechnology Reports
Institutions: Chulalongkorn University, BOKU University
Language: English
Subfield: Biotechnology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,070
Award: G9001166459
OpenAlex ID: W4404787255