Metabolic engineering of Escherichia coli to produce succinic acid

被引：0
作者：
Tang W. [1 ,2 ]
Wang X. [1 ,2 ]
Guo L. [1 ,2 ]
Ji L. [1 ,2 ]
Gao C. [1 ,2 ]
Chen X. [1 ,2 ]
Liu L. [1 ,2 ]
机构：
[1] State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi
[2] International Joint Laboratory on Food Safety, Jiangnan University, Wuxi
来源：
Huagong Jinzhan/Chemical Industry and Engineering Progress | 2022年 / 41卷 / 02期
关键词：
By-products; Cofactors recycle; Combined mutagenesis; E; coli; Fermentation optimization; Succinic acid;
D O I：
10.16085/j.issn.1000-6613.2021-0531
中图分类号：
学科分类号：
摘要：
Succinic acid is a four-carbon dicarboxylic acid, which is widely used in food, medicine, plastics and chemical industries. Microbial production of succinic acid has problems such as low yield, low productivity and by-products accumulation. In this study, through compound mutagenesis (ARTP and 60Co-γ), a high osmotic pressure-tolerant mutant strain FMME-N-2 was screened, with a succinic acid yield of 0.70g/gglucose and an accumulation of 18.8g/L lactic acid, 7.6g/L formic acid and 17.3g/L acetic acid. To decrease the accumulation of by-products and further increase succinic acid yields, the strain FMME-N-13 with a yield of 0.92g/gglucose was constructed by deleting the genesof ldhA, pflB-focA, pta, tdcD, and tdcE, accumulating 0.6g/L lactic acid, 3.6g/L formic acid and 12.3g/L acetic acid. At the same time, the control of RBS intensity combined with optimizing the level of AsPCK (Actinobacillus succinogenes phosphoenolpyruvate carboxykinase) and CbFDH (Candida boidinii formate dehydrogenase) was used to regulate the concentration of intracellular ATP and NADH, and the succinic acid yield of engineering strain FMME-N-26 (FMME-N-13-L-AsPCK-L-CbFDH) increased to 1.04g/g glucose only with an accumulation of 5.5g/L acetic acid. Finally, the glucose concentration of the anaerobic stage was optimized. When the glucose concentration was controlled at 0-5g/L, succinic acid titer of the strain FMME-N-26 was increased to 111.9g/L, with a yield of 1.11g/g glucose (99% of the theoretical yield) and a productivity of 1.76g/L/h, showing great potential for industrial production. © 2022, Chemical Industry Press Co., Ltd. All right reserved.
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页码：938 / 950
页数：12
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