State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dong-Chuan Road, Shanghai, 200240, China.
Biotechnol Adv. 2012 Nov-Dec;30(6):1301-8. doi: 10.1016/j.biotechadv.2011.10.001. Epub 2011 Oct 18.
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.
近年来，二次代谢信号转导工程作为一种高效生产有价值的次生代谢产物的有力工具，受到了极大的关注。本研究发现钙调神经磷酸酶信号转导对高等真菌（蘑菇）三萜生物合成有重要意义。向灵芝（一种著名的传统药用蘑菇）的静态液体培养物中添加钙离子（10mM）被证明是一种有效的策略，可以提高抗肿瘤灵芝酸（GAs）的产量，分别使总 GAs、GA-Mk、-T、-S 和 -Me 的产量提高了 3.7 倍、2.6 倍、4.5 倍、3.2 倍和 3.8 倍。使用 Ca2+传感器抑制剂的实验表明，钙调神经磷酸酶信号参与调节 GAs 生物合成。定量基因转录分析显示，添加钙离子后，GAs 生物合成和 Ca2+传感器的基因表达水平上调，而添加抑制剂后则下调，表明较高的 GAs 产量可能是由于这些基因的较高表达所致。基于所获得的结果，提出了一种外源性钙离子通过钙调神经磷酸酶信号转导途径影响 GAs 生物合成的可能模型。
