Induction and sustainable production of cannabinoids in Cannabis sativa L. callus cultures using Yarrowia lipolytica biogenic silver nanoparticles

Cannabis sativa L. produces cannabinoids as high-value secondary metabolites within the specialized glandular trichomes of mature inflorescences. Large-scale cannabinoid production in conventional agriculture is limited due to extensive land requirements, irrigation requirements, pests and diseases, and reliance on agrochemicals. In vitro platforms offer a reliable and climate-independent alternative for the production of plant-derived compounds. However, cannabinoid biosynthesis in undifferentiated callus tissues remains poorly understood because these tissues lack specialized morphological structures. This study presents an innovative strategy to induce and sustainable production of cannabinoids in C. sativa callus cultures using biogenic silver nanoparticles (AgNPs) synthesized via Yarrowia lipolytica . After treatment of C. sativa L. callus cultures with biogenic AgNPs, cannabinoids (THC and CBD) were quantified by HPLC and the expression of key biosynthetic genes ( CBDAS and THCAS ) was analyzed by qPCR. In the control samples, cannabinoids were not detectable. Treatment with 20 mg/L AgNPs led to accumulation of THC (0.31%) and CBD (0.26%). Results of qPCR confirmed upregulation of the biosynthetic genes CBDAS and THCAS . These green AgNPs acted as potent signaling triggers and induce a significant metabolic shift in the callus cultures. This is the first report demonstrating the effectiveness of biogenic AgNPs in inducing cannabinoid biosynthesis in C. sativa L. callus cultures. These findings highlight a sustainable and eco-friendly approach for the industrial production of plant-derived medicinal compounds.