食品与发酵工业2023，Vol.49Issue(24)：8-14,7.DOI:10.13995/j.cnki.11-1802/ts.035020
大肠杆菌合成烟酰胺单核苷酸途径构建及发酵工艺研究
Construction and fermentation process of nicotinamide mononucleotide synthesis by Escherichia coli
摘要
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 heter-ologous in E.coli,and a remedial synthesis pathway for NMN was constructed.In order to enhance the supply of the precursor 5-phos-phate 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.关键词
代谢网络/基因调控/烟酰胺单核苷酸/5-磷酸核糖1-焦磷酸/发酵工艺Key words
metabolic network/gene regulation/nicotinamide mononucleotide/5-phosphoribosyl 1-pyrophosphate/fermentation引用本文复制引用
程琳,龚劲松,Michael HALL,苏畅,徐国强,许正宏,史劲松..大肠杆菌合成烟酰胺单核苷酸途径构建及发酵工艺研究[J].食品与发酵工业,2023,49(24):8-14,7.基金项目
国家自然基金面上项目(21978116) （21978116）
江苏省自然基金(BK20221082) （BK20221082）
中央高校基本科研业务费专项资金(JUSRP22047) （JUSRP22047）
