Induction of ganoderic acid biosynthesis by Mn2+ in static liquid cultivation of Ganoderma lucidum.

Metal ions affect cell physiology and metabolism significantly, but the role of Mn(2+) in the secondary metabolism of mushrooms is yet unclear. In static liquid cultivation of Ganoderma lucidum for producing antitumor ganoderic acids (GAs), the Mn(2+) addition was performed. Addition of 10 mM Mn(2+) at the start of the static liquid cultivation resulted in 2.2-fold improvement of total GAs production. The expression levels of GA biosynthetic and Ca(2+) sensors' genes were up-regulated with Mn(2+) induction while down-regulated by adding cyclosporin A (calcineurin inhibitor), suggesting that higher GA production might result from calcineurin signal regulation. Intracellular Ca(2+) imaging and calcineurin inhibitor study revealed that addition of Mn(2+) led to Ca(2+) influx from medium to the cells to trigger calcineurin signals. Mn(2+) addition was therefore an efficient induction strategy for improving GAs production, whose regulation mechanism was via calcineurin signaling transduction.