异丁醇
代谢工程
发酵
糖异生
代谢通量分析
化学
生物化学
焊剂(冶金)
微生物代谢
丙酮酸
丙酮酸脱氢酶复合物
代谢途径
柠檬酸循环
丙酮酸脱羧
新陈代谢
细菌
生物过程
生物
酶
有机化学
乙醇
古生物学
遗传学
作者
Yuki Soma,Taiki Yamaji,Taizo Hanai
标识
DOI:10.1016/j.jbiosc.2021.09.015
摘要
Pyruvate is a key intermediate that is involved in various synthetic metabolic pathways for microbial chemical and fuel production. It is widely used in the food, chemical, and pharmaceutical industries. However, the microbial production of pyruvate and its derivatives compete with microbial cell growth, as pyruvate is an important metabolic intermediate that serves as a hub for various endogenous metabolic pathways, including gluconeogenesis, amino acid synthesis, TCA cycle, and fatty acid biosynthesis. To achieve a more efficient bioprocess for the production of pyruvate and its derivatives, it is necessary to reduce the metabolic imbalance between cell growth and target chemical production. For this purpose, we devised a dynamic metabolic engineering strategy within an Escherichia coli model, in which a metabolic toggle switch (MTS) was employed to redirect metabolic flux from the endogenous pathway toward the target synthetic pathway. Through a combination of TCA cycle interruption through MTS and reduction of pyruvate consumption in endogenous pathways, we achieved a drastic improvement (163 mM, 26-fold) in pyruvate production. In addition, we demonstrated the redirection of metabolic flux from excess pyruvate toward isobutanol production. The final isobutanol production titer of the strain harboring MTS was 26% improved compared with that of the control strain.
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