Cytoplasmic Mevalonate Pathways Play Major Roles in Ginsenoside Production and Mevinolin Treatment Activates the Plastidic 2-C-Methyl-D-erythritol 4-Phosphate (MEP) Pathway

Once squalene is cyclized into 2,3-oxidosqualene, ginsenosides are biosynthesized by the activity of dammarenediol-II synthase following hydroxylation and glycosylation steps. Final ginsenoside content is regulated by the levels of isopentenyl diphosphate and dimethylallyl diphosphate formation in the isoprenoid pathway. Thus, ginsenoside biosynthesis is normally modulated via the mevalonic acid (MVA) pathway and via the deoxy-xylulose 5-phosphate/2-C-methyl-D-erythritol 4-phosphate (MEP) pathway. In order to elucidate which pathway is involved in the production of ginsenosides in Panax ginseng Meyer, both pathways were tested using inhibitors. Mevinolin treatment for 3 days reduced the concentrations of seven major ginsenosides by up to 36%, whereas fosmidomycin reduced concentrations by up to 13.2%. The intermediate MVA compound mevalonate did not affect the total amount of ginsenosides, but fluctuation between individuals was observed. Mevinolin treatment in model Arabidopsis plants resulted in increased chlorophyll and carotenoid content, and these systems were found to be applicable in ginseng.