Metabolic design for selective production of nicotinamide mononucleotide from glucose and nicotinamide

?-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 highactivity 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 lowcost, high-quality industrial production of NMN and other nucleotide compounds using microorganisms.

Automated summary

A whole-cell biocatalyst using Escherichia coli was developed for efficient production of Nicotinamide mononucleotide (NMN) from inexpensive substrates glucose and nicotinamide, achieving high yields and selectivity. The approach identified functional transporters and key enzymes allowing for intracellular uptake, conversion, and extracellular excretion of NMN. This method shows promise for low-cost, high-quality industrial production of NMN and other nucleotide compounds using microorganisms.