Impacts of calcium signal transduction on the fermentation production of antitumor ganoderic acids by medicinal...

Recently signal transduction engineering of secondary metabolism is receiving great interest as a powerful tool towards efficient production of valuable secondary metabolites. This work found that the calcineurin-signal transduction was significant to triterpene biosynthesis by higher fungus (mushroom). Addition of calcium ion (at 10mM) to static liquid cultures of Ganoderma lucidum, a famous traditional medicinal mushroom, was proved as a useful strategy to enhance the production of antitumor ganoderic acids (GAs), which resulted in 3.7-, 2.6-, 4.5-, 3.2- and 3.8-fold improvement of total GAs, individual GA-Mk, -T, -S, and -Me, respectively. Experiments using Ca2+ sensor inhibitors indicated the involvement of calcineurin signal in regulating GAs biosynthesis. Quantitative gene transcription analysis revealed that the expression levels of genes of GAs biosynthesis and Ca2+ sensor were up-regulated with calcium addition while down-regulated under the inhibitors addition, suggesting that higher GAs production may be resulted from higher expressions of those genes. Based on the results obtained, a possible model on the effect of external calcium ion on the GAs biosynthesis via calcineurin signal transduction pathway was proposed.