Induction of ganoderic acid biosynthesis by Mn 2+ 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. Biotechnol. Bioeng. 2014;111: 2358–2365. © 2014 Wiley Periodicals, Inc.