Hou Jianshen, Gao Cong, Chen Xiulai, Liu Liming
State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, Jiangsu, China.
Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, Jiangsu, China.
Sheng Wu Gong Cheng Xue Bao. 2020 Oct 25;36(10):2104-2112. doi: 10.13345/j.cjb.200078.
Shikimic acid is an intermediate metabolite in the synthesis of aromatic amino acids in Escherichia coli and a synthetic precursor of Tamiflu. The biosynthesis of shikimic acid requires blocking the downstream shikimic acid consuming pathway that leads to inefficient production and cell growth inhibition. In this study, a dynamic molecular switch was constructed by using growth phase-dependent promoters and degrons. This dynamic molecular switch was used to uncouple cell growth from shikimic acid synthesis, resulting in the production of 14.33 g/L shikimic acid after 72 h fermentation. These results show that the dynamic molecular switch could redirect the carbon flux by regulating the abundance of target enzymes, for better production.
莽草酸是大肠杆菌中芳香族氨基酸合成的中间代谢产物,也是达菲的合成前体。莽草酸的生物合成需要阻断下游消耗莽草酸的途径,该途径会导致生产效率低下和细胞生长抑制。在本研究中,利用生长阶段依赖性启动子和降解子构建了一个动态分子开关。这个动态分子开关用于将细胞生长与莽草酸合成解偶联,在72小时发酵后产生了14.33 g/L的莽草酸。这些结果表明,动态分子开关可以通过调节靶酶的丰度来重新引导碳通量,以实现更好的生产。