State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China.
School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, China.
Biotechnol Bioeng. 2020 Nov;117(11):3533-3544. doi: 10.1002/bit.27485. Epub 2020 Jul 21.
Microbial cell factories are widely used for the production of high-value chemicals. However, maximizing production titers is made difficult by the complicated regulatory mechanisms of these cell platforms. Here, k values were incorporated to construct an Escherichia coli enzyme-constrained model. The resulting ec_iML1515 model showed that the protein demand and protein synthesis rate were the key factors affecting lysine production. By optimizing the expression of the 20 top-demanded proteins, lysine titers reached 95.7 ± 0.7 g/L, with a 0.45 g/g glucose yield. Moreover, adjusting NH and dissolved oxygen levels to regulate the synthesis rate of energy metabolism-related proteins caused lysine titers and glucose yields to increase to 193.6 ± 1.8 g/L and 0.74 g/g, respectively. The ec_iML1515 model provides insight into how enzymes required for the biosynthesis of certain products are distributed between and within metabolic pathways. This information can be used to accurately predict and rationally design lysine production.
微生物细胞工厂被广泛用于生产高价值化学品。然而，这些细胞平台复杂的调控机制使得产量最大化变得困难。在这里，k 值被引入来构建大肠杆菌酶限制模型。所得的 ec_iML1515 模型表明，蛋白质需求和蛋白质合成率是影响赖氨酸产量的关键因素。通过优化 20 种需求量最大的蛋白质的表达，赖氨酸产量达到 95.7±0.7 g/L，葡萄糖得率为 0.45 g/g。此外，调节 NH 和溶解氧水平以调节与能量代谢相关的蛋白质的合成率，导致赖氨酸产量和葡萄糖得率分别增加到 193.6±1.8 g/L 和 0.74 g/g。ec_iML1515 模型提供了关于某些产品生物合成所需的酶如何在代谢途径之间和内部分配的见解。这些信息可用于准确预测和合理设计赖氨酸生产。
