Development of probiotic E. coli Nissle 1917 for beta-alanine production by using protein and metabolic engineering
文献类型： 外文期刊
作者： Hu, Shilong 1 ; Fei, Mingyue 1 ; Fu, Beibei 1 ; Yu, Mingjing 1 ; Yuan, Panhong 1 ; Tang, Biao 2 ; Yang, Hua 2 ; Sun, Dongchang 1 ;
作者机构： 1.Zhejiang Univ Technol, Coll Biotechnol & Bioengn, Hangzhou 310014, Zhejiang, Peoples R China
2.Zhejiang Acad Agr Sci, Inst Qual & Stand Agroprod, Hangzhou 310021, Zhejiang, Peoples R China
关键词： Escherichia coli Nissle 1917; beta-Alanine; Aspartate-alpha-decarboxylase; Genetic engineering; Fed-batch fermentation
期刊名称：APPLIED MICROBIOLOGY AND BIOTECHNOLOGY （ 影响因子：5.0； 五年影响因子：5.2 ）
ISSN： 0175-7598
年卷期： 2023 年
页码：
收录情况： SCI
摘要： beta-alanine has been used in food and pharmaceutical industries. Although Escherichia coli Nissle 1917 (EcN) is generally considered safe and engineered as living therapeutics, engineering EcN for producing industrial metabolites has rarely been explored. Here, by protein and metabolic engineering, EcN was engineered for producing beta-alanine from glucose. First, an aspartate-alpha-decarboxylase variant ADC(K43Y) with improved activity was identified and over-expressed in EcN, promoting the titer of beta-alanine from an undetectable level to 0.46 g/L. Second, directing the metabolic flux towards L-aspartate increased the titer of beta-alanine to 0.92 g/L. Third, the yield of beta-alanine was elevated to 1.19 g/L by blocking conversion of phosphoenolpyruvate to pyruvate, and further increased to 2.14 g/L through optimizing culture medium. Finally, the engineered EcN produced 11.9 g/L beta-alanine in fed-batch fermentation. Our work not only shows the potential of EcN as a valuable industrial platform, but also facilitates production of beta-alanine via fermentation.
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