Biological production of nicotinamide mononucleotide: a review

Nicotinamide mononucleotide (NMN) presents significant therapeutic potential against aging-related conditions, such as Alzheimer's disease, due to its consistent and strong pharmacological effects. Aside from its anti-aging effect, NMN is also an emerging noncanonical cofactor for orthogonal metabolic pathways in the field of biomanufacturing. This has significant advantages in the field of metabolic engineering, allowing cells to produce unnatural chemicals without disrupting the natural cellular processes. NMN is produced through both the chemical and biological methods, with the latter being more environmentally sustainable. The primary biological production pathway centers on the enzyme nicotinamide phosphoribosyltransferase, which transforms nicotinamide and phosphoribosyl pyrophosphate to NMN. Efforts to increase NMN production have been explored in microorganisms, such as: Escherichia coli, Bacillus subtilis, and yeast, serving as biocatalysts, by rewiring their metabolic processes. Although most researchers are focusing on genetically and metabolically manipulating microorganisms to act as biocatalysts, a growing number of studies on cell-free synthesis are emerging as a promising strategy for producing NMN. This review explores the different biological production techniques of NMN employing microorganisms. This article, in particular, is essential to those who are working on NMN production using microbial strain engineering and cell-free systems.