Construction and fermentation process of nicotinamide mononucleotide synthesis by Escherichia coli

  • CHENG Lin ,
  • GONG Jinsong ,
  • Michael HALL ,
  • SU Chang ,
  • XU Guoqiang ,
  • XU Zhenghong ,
  • SHI Jinsong
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  • 1(Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China)
    2(School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China)
    3(National Engineering Research Center for Cereal Fermentation and Food Biomanufacturing, Jiangnan University, Wuxi 214122, China)
    4(Seragon Biosciences, Inc., Irvine 92618, United States)

Received date: 2023-02-04

  Revised date: 2023-02-17

  Online published: 2024-01-17

Abstract

β-nicotinamide mononucleotide (NMN) as the direct precursor of the important coenzyme NAD+ in the human body has received widespread attention, and the current industry mainly uses chemical method or chemical-enzyme catalytic method for synthesis, and the fermentation method has not yet made a breakthrough. In order to obtain an engineered strain with high NMN yield, the metabolic pathway of Escherichia coli was modified. Firstly, nicotinamide phosphoribosyl transferase from Chitinophaga pinensis was expressed heterologous in E. coli, and a remedial synthesis pathway for NMN was constructed. In order to enhance the supply of the precursor 5-phosphate ribose-1-pyrophosphate (PRPP), multiple pathway enzymes originating from glucose were expressed, which promoted the flow of glucose to the pentose phosphate pathway; Further, in order to facilitate the accumulation of NMN, by knocking out the NMN downstream metabolic catalysis pathway genes pncC and ushA and regulating the NAD+ derivative gene nadR, the yield of recombinant strain obtained reached 60 mg/L, notably, which was 4.95 times over the initial level, and the fermentation was further performed on a 5 L fermenter, and the yield reached 390.1 mg/L. The strain exhibits significant potential for fermentation production of NMN.

Cite this article

CHENG Lin , GONG Jinsong , Michael HALL , SU Chang , XU Guoqiang , XU Zhenghong , SHI Jinsong . Construction and fermentation process of nicotinamide mononucleotide synthesis by Escherichia coli[J]. Food and Fermentation Industries, 2023 , 49(24) : 8 -14 . DOI: 10.13995/j.cnki.11-1802/ts.035020

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