Green manufacturing synthesis of nicotinamide mononucleotide: Pathways, catalysts, and prospects

Functional coenzymes, a class of organic small-molecule cofactors, play essential roles in enzyme-catalyzed reactions. They participate in key biological processes, including redox reactions, group transfers, and isomerization, through transient association with enzyme proteins. As vital components for sustaining enzymatic activity and cellular energy metabolism, functional coenzymes are experiencing rapidly growing market demand, driven by global population aging and increasing health awareness worldwide. Biomanufacturing technologies can better meet this market need by enhancing production efficiency, lowering costs, and fostering product innovation, thereby injecting new vitality into the industry. Using β-nicotinamide mononucleotide (NMN) as a representative functional coenzyme, this article systematically reviews the current state of coenzyme synthesis technologies. Special emphasis is placed on multi-strategy approaches applied in the fermentative and enzymatic synthesis of NMN, covering enzyme classification, cofactor regeneration, competitive pathway modulation, and transport system optimization. The screening, engineering, and application of key enzymes, together with interdisciplinary research directions such as systems metabolic engineering and coupled fermentation process optimization, are proposed to drive continuous innovation in coenzyme biomanufacturing. These efforts will provide a solid foundation for the high-quality development of the coenzyme industry and enhance its international competitiveness.