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Metabolic engineering of Escherichia coli for the production of four-carbon dicarboxylic acids
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Yongsheng TANG, Deyang DING, Zhe ZHANG, Xiulai CHEN
Acta Microbiologica Sinica | 2026, 66(5) : 2159 - 2173
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Acta Microbiologica Sinica | 2026, 66(5): 2159-2173
Research Article
Metabolic engineering of Escherichia coli for the production of four-carbon dicarboxylic acids
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Yongsheng TANG, Deyang DING, Zhe ZHANG, Xiulai CHEN
Affiliations
  • School of Biotechnology and Key Laboratory of Industrial Biotechnology of Ministry of Education, Jiangnan University, Wuxi, Jiangsu, China
Published: 2026-05-04 doi: 10.13343/j.cnki.wsxb.20250830
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Objective Four-carbon dicarboxylic acids are a class of important platform chemicals widely used in the food, pharmaceutical, and chemical industries. However, the efficiency of microbial fermentation for producing four-carbon dicarboxylic acids still faces challenges, mainly limited by insufficient central carbon metabolic flux and byproduct accumulation. Methods This study used Escherichia coli as the chassis strain and adopted a strategy combining rational metabolic engineering and non-rational modification to systematically optimize the four-carbon dicarboxylic acid synthesis capacity of E. coli. Results The non-cyclic glyoxylate shunt was reconstructed and the expression of key pathway enzymes was optimized to enhance the metabolic flux toward four-carbon dicarboxylic acids. The synthesis capacity of four-carbon dicarboxylic acids was enhanced by employing atmospheric and room-temperature plasma (ARTP) mutagenesis. The knockout of key genes in the acetate, formate, and lactate synthesis pathways effectively minimized carbon flux diversion, thereby enhancing the availability of oxaloacetate, the central precursor to four-carbon dicarboxylic acids. On this basis, through specific modification of terminal metabolic pathways, the engineering strain E. coli Fum02 for fumaric acid production were constructed. Finally, in a 5 L fermenter, the fumaric acid titer, yield, and productivity of the engineering strain E. coli Fum02 reached 45.2 g/L, 0.45 g/g, and 0.23 g/(L·h), respectively. Furthermore, by blocking the succinate dehydrogenase gene (sdhAB) and implementing fermentation optimization strategies, this platform strain could also be redirected toward efficient succinate production. Conclusion This study provides a reference for the metabolic engineering modification of bacteria to produce organic acids and also lays a foundation for the industrial biomanufacturing of four-carbon dicarboxylic acids.

Escherichia coli  /  four-carbon dicarboxylic acids  /  metabolic engineering  /  cell factory
Yongsheng TANG, Deyang DING, Zhe ZHANG, Xiulai CHEN. Metabolic engineering of Escherichia coli for the production of four-carbon dicarboxylic acids[J]. Acta Microbiologica Sinica, 2026 , 66 (5) : 2159 -2173 . DOI: 10.13343/j.cnki.wsxb.20250830
  • The National Natural Science Foundation of China(32571712)
  • The Basic Research Program of Jiangsu and Jiangsu Basic Research Center for Synthetic Biology(BK20233003)
  • The Fundamental Research Funds for the Central Universities(JUSRP124023)
Year 2026 volume 66 Issue 5
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Article Info
doi: 10.13343/j.cnki.wsxb.20250830
  • Receive Date:2025-11-05
  • Online Date:2026-05-09
  • Published:2026-05-04
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History
  • Received:2025-11-05
  • Accepted:2025-12-24
Funding
The National Natural Science Foundation of China(32571712)
The Basic Research Program of Jiangsu and Jiangsu Basic Research Center for Synthetic Biology(BK20233003)
The Fundamental Research Funds for the Central Universities(JUSRP124023)
Affiliations
    School of Biotechnology and Key Laboratory of Industrial Biotechnology of Ministry of Education, Jiangnan University, Wuxi, Jiangsu, China

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表12种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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