Li Huan-Jun, Zhang De-Huai, Han Li-Liang, Yu Xuya, Zhao Peng, Li Tao, Zhong Jian-Jiang, Xu Jun-Wei
Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, 650500, China.
State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dong-chuan Road, Shanghai, 200240, China.
Bioprocess Biosyst Eng. 2016 Jan;39(1):75-80. doi: 10.1007/s00449-015-1491-7. Epub 2015 Oct 27.
To further improve the ganoderic acid (GA) production, a novel integrated strategy by combining nitrogen limitation and calcium ion addition was developed. The effects of the integrated combination on the content of GA-T (one powerful anticancer compound), their intermediates (squalene and lanosterol) and on the transcription levels of GA biosynthetic genes in G. lucidum fermentation were investigated. The maximum GA-T content with the integrated strategy were 1.87 mg/ 100 mg dry cell weight, which was 2.1-4.2 fold higher than that obtained with either calcium ion addition or nitrogen limitation alone, and it is also the highest record as ever reported in submerged fermentation of G. lucidum. The squalene content was increased by 3.9- and 2.2-fold in this case compared with either individual strategy alone. Moreover, the transcription levels of the GA biosynthetic genes encoding 3-hydroxy-3-methyglutaryl coenzyme A reductase and lanosterol synthase were also up-regulated by 3.3-7.5 and 1.3-2.3 fold, respectively.
为进一步提高灵芝酸（GA）产量，开发了一种结合氮限制和添加钙离子的新型综合策略。研究了该综合策略对GA-T（一种强效抗癌化合物）及其中间体（角鲨烯和羊毛甾醇）含量以及灵芝发酵中GA生物合成基因转录水平的影响。采用该综合策略时，GA-T的最大含量为1.87mg/100mg干细胞重量，比单独添加钙离子或单独进行氮限制时获得的含量高出2.1至4.2倍，这也是灵芝深层发酵中迄今报道的最高记录。与单独采用任何一种策略相比，此时角鲨烯含量分别提高了3.9倍和2.2倍。此外，编码3-羟基-3-甲基戊二酰辅酶A还原酶和羊毛甾醇合酶的GA生物合成基因的转录水平也分别上调了3.3至7.5倍和1.3至2.3倍。
