β-Nicotinamide mononucleotide (NMN) is, one of the nucleotide compounds, a precursor of NAD⁺ and has recently attracted attention as a nutraceutical. Here, we develop a whole-cell biocatalyst using Escherichia coli, which enabled selective and effective high production of NMN from the inexpensive feedstock substrates glucose and nicotinamide (Nam). Notably, we identify two actively functional transporters (NiaP and PnuC) and a high-activity key enzyme (Nampt), permitting intracellular Nam uptake, efficient conversion of phosphoribosyl pyrophosphate (PRPP; supplied from glucose) and Nam to NMN, and NMN excretion extracellularly. Further, enhancement of the PRPP biosynthetic pathway and optimization of individual gene expression enable drastically higher NMN production than reported thus far. The strain extracellularly produces 6.79 g l-1 of NMN from glucose and Nam, and the reaction selectivity from Nam to NMN is 86%. Our approach will be promising for low-cost, high-quality industrial production of NMN and other nucleotide compounds using microorganisms.

β-烟酰胺单核苷酸 (NMN) 是核苷酸化合物之一，是 NAD ⁺的前体，最近作为营养品受到关注。在这里，我们开发了一种使用大肠杆菌的全细胞生物催化剂，这使得能够从廉价的原料底物葡萄糖和烟酰胺 (Nam) 中选择性和有效地高产 NMN。值得注意的是，我们确定了两种活跃的功能性转运蛋白（NiaP 和 PnuC）和一种高活性关键酶（Nampt），允许细胞内的 Nam 摄取、磷酸核糖焦磷酸（PRPP；由葡萄糖提供）和 Nam 向 NMN 的有效转化，以及 NMN 在细胞外的排泄. 此外，PRPP 生物合成途径的增强和个体基因表达的优化使得 NMN 产量比迄今为止报道的要高得多。该菌株从葡萄糖和 Nam 细胞外产生 6.79 g l-1 NMN，从 Nam 到 NMN 的反应选择性为 86%。我们的方法将有望用于使用微生物低成本、高质量地工业生产 NMN 和其他核苷酸化合物。