Plant cells and medicinal mushrooms are a treasury of therapeutically bioactive agents. Ginsenosides are an important group of tetracyclic triterpene glycosides produced by Panax ginseng, a well-known traditional Chinese medicinal plant, and the versatile pharmacological activities of ginsenosides include hypocholesterolemic, antitumor, immunoadjuvant and anti-inflammatory functions. Ganoderic acids (GAs) produced by Ganoderma lucidum, a traditional Chinese medicinal mushroom, have significant pharmacological activities such as anti-tumor, anti-metastasis and anti-HIV. Both ginsenosides and GAs are synthesized through the mevalonate/isopenoid pathway, but the details of later steps in their biosynthetic pathways are yet unclear. The fact implies that construction of heterologous biosynthetic pathway of them in other hosts is not feasible at this stage, and fermentation engineering of those culture systems is interesting to their commercial utilization.
Signal transduction engineering is important to improve secondary metabolite production. In this work, the effects of various elicitors on the ginsenoside and GAs biosynthesis in liquid cultures of P. ginseng and G. lucidum were investigated. For example, the optimal concentration and time of vanadate addition for ginsenoside biosynthesis and Mn2+ addition for GAs biosynthesis were identified. The increased activities of key enzymes and up-regulation of transcriptional levels of genes encoding enzymes in the triterpenes’ biosynthesis were observed. The regulation mechanism of Mn2+ on the GA biosynthesis was found via the calcineurin signaling transduction, and the stimulation of the ginsenoside biosynthesis by vanadate was at least partially through the signal molecule jasmonic acid. This work demonstrated that elicitor manipulation was an efficient induction strategy, having significantly improved the production of ginsenosides and GAs in those fermentation systems. The approach of signal transduction engineering is considered useful to the large-scale production of ginsenosides, GAs, and other bioactive secondary metabolites in plant-cell and mushroom-mycelial fermentations.
