Regulation of intracellular level of ATP and NADH in <i>Escherichia coli</i> to promote succinic acid production.

Xueming Wang; Jingyu Pan; Jing WU; Xiulai Chen; Cong Gao; Wei Song; Wanqing Wei; Jia Liu; Liming Liu

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Regulation of intracellular level of ATP and NADH in Escherichia coli to promote succinic acid production.

Author: Xueming WANG ¹ ; Jingyu PAN ¹ ; Jing WU ² ; Xiulai CHEN ¹ ; Cong GAO ¹ ; Wei SONG ² ; Wanqing WEI ² ; Jia LIU ¹ ; Liming LIU ¹
Author Information

1. State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, Jiangsu, China.
2. School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, Jiangsu, China.
Publication Type:Journal Article
Keywords: Escherichia coli; cofactor balance; metabolic engineering; succinic acid
MeSH: Escherichia coli/genetics*; NAD; Succinic Acid; Acetic Acid; Adenosine Triphosphate
From: Chinese Journal of Biotechnology 2023;39(8):3236-3252
CountryChina
Language:Chinese
Abstract: Succinic acid is an important C4 platform chemical that is widely used in food, chemical, medicine sectors. The bottleneck of fermentative production of succinic acid by engineered Escherichia coli is the imbalance of intracellular cofactors, which often leads to accumulation of by-products, lower yield and low productivity. Stoichiometric analysis indicated that an efficient production of succinic acid by E. coli FMME-N-26 under micro-aeration conditions might be achieved when the TCA cycle provides enough ATP and NADH for the r-TCA pathway. In order to promote succinic acid production, a serial of metabolic engineering strategies include reducing ATP consumption, strengthening ATP synthesis, blocking NADH competitive pathway and constructing NADH complementary pathway were developed. As result, an engineered E. coli FW-17 capable of producing 139.52 g/L succinic acid and 1.40 g/L acetic acid in 5 L fermenter, which were 17.81% higher and 67.59% lower than that of the control strain, was developed. Further scale-up experiments were carried out in a 1 000 L fermenter, and the titer of succinic acid and acetic acid were 140.2 g/L and 1.38 g/L, respectively.