大肠杆菌
柠檬酸
底盘
食品科学
化学
柠檬酸循环
发酵
微生物学
生物
生物化学
基因
新陈代谢
工程类
结构工程
作者
Hougang Zhou,Y. Z. Zhang,Christopher P. Long,Xuesen Xia,Yanfen Xue,Yanhe Ma,Maciek R. Antoniewicz,Yong Tao,Bo-Kun Lin
标识
DOI:10.1038/s41467-024-46655-4
摘要
Abstract Tricarboxylic acid cycle (TCA cycle) plays an important role for aerobic growth of heterotrophic bacteria. Theoretically, eliminating TCA cycle would decrease carbon dissipation and facilitate chemicals biosynthesis. Here, we construct an E. coli strain without a functional TCA cycle that can serve as a versatile chassis for chemicals biosynthesis. We first use adaptive laboratory evolution to recover aerobic growth in minimal medium of TCA cycle-deficient E. coli . Inactivation of succinate dehydrogenase is a key event in the evolutionary trajectory. Supply of succinyl-CoA is identified as the growth limiting factor. By replacing endogenous succinyl-CoA dependent enzymes, we obtain an optimized TCA cycle-deficient E. coli strain. As a proof of concept, the strain is engineered for high-yield production of four separate products. This work enhances our understanding of the role of the TCA cycle in E. coli metabolism and demonstrates the advantages of using TCA cycle-deficient E. coli strain for biotechnological applications.
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