State Key Lab of Bioreactor Engineering, Newworld Institute of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China.
Huzhou University, College of Life Science, Huzhou, China.
J Biotechnol. 2020 May 20;314-315:1-7. doi: 10.1016/j.jbiotec.2020.03.010. Epub 2020 Apr 3.
l-homoserine is an important functional amino acid. Based on the system metabolic engineering strategy, the key genes in the central metabolic pathway of Escherichia coli W3110 were engineered to construct the strain for l-homoserine production. To construct an engineered strain with high yield of l-homoserine, the work was carried out from the following aspects: (1) Disrupt the competitive and degradative pathways of l-homoserine, and the l-homoserine was initially accumulated with a titer of 0.2 g/L; (2) Exploring the effect of weakening TCA cycle, modification of the glyoxylate branch, and reduction of the pyruvate synthesis for l-homoserine synthesis. The concentration of l-homoserine in the final recombinant strain LJL12 reached a titer of 3.2 g/L at shake flask and 35.8 g/L in fed-batch fermentation, showing a high l-homoserine production capacity (0.82 g/L/h). The study provides a well research foundation for l-homoserine production with the capacity for industrial application.
L-高丝氨酸是一种重要的功能性氨基酸。基于系统代谢工程策略，对大肠杆菌 W3110 中心代谢途径中的关键基因进行工程改造，构建用于 L-高丝氨酸生产的菌株。为了构建产 L-高丝氨酸产量高的工程菌株，从以下几个方面开展工作：（1）阻断 L-高丝氨酸的竞争和降解途径，使 L-高丝氨酸初步积累至 0.2g/L；（2）探索减弱三羧酸循环、修饰乙醛酸支路和降低丙酮酸合成对 L-高丝氨酸合成的影响。最终重组菌株 LJL12 在摇瓶和补料分批发酵中的 L-高丝氨酸浓度分别达到 3.2g/L 和 35.8g/L，具有较高的 L-高丝氨酸生产能力（0.82g/L/h）。该研究为具有工业应用能力的 L-高丝氨酸生产提供了良好的研究基础。
