Impacts of calcium signal transduction on the fermentation production of antitumor ganoderic acids by medicinal mushroom Ganoderma lucidum.
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.
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dong-Chuan Road, Shanghai, 200240, China.
Yi-Ning
YN
Xu
Jian-Jiang
JJ
Zhong
D000363:Agaricales / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D018533:Biomass; D053898:Biosynthetic Pathways / Q000187:drug effects / Q000235:genetics; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects* / Q000235:genetics; D005285:Fermentation / Q000187:drug effects*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005800:Genes, Fungal / Q000235:genetics; D007477:Ions; D008954:Models, Biological; D020940:Reishi / Q000737:chemistry*; D013172:Spores, Fungal / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014315:Triterpenes / Q000138:chemical synthesis*
D000970:Antineoplastic Agents; D007477:Ions; D014315:Triterpenes; C556862:ganoderic acid; D019703:Calcineurin; D002118:Calcium