Microbial Production of Nicotinamide Mononucleotide: Key Enzymes Discovery, Host Cells Selection, and Pathways Design and Optimization.

As an important bioactive substance in cells, nicotinamide mononucleotide (NMN) has been proven to play an important role in antiaging, treatment of neurodegenerative diseases, and cardioprotection. It presents a high potential for application in the research fields of functional foods, cosmetics, healthcare products, and active pharmaceuticals. With the increased demand, whether NMN can achieve large-scale industrial production has been a wide concern. The chemical synthesis method of NMN mainly faces the problems of separation, purification, and complex process control; in contrast, biosynthesis methods such as microbial fermentation and enzyme catalysis are considered to be the mainstream of the future industrial production of NMN due to the advantages of environmental friendliness, high efficiency, and simple separation. This review first describes the physiological functions of NMN and the related areas of its applications. Subsequently, it focuses on the research progress on different synthetic pathways of NMN in biosynthetic approaches, mining and modification of key enzymes, chassis cell design and optimization, and whole-cell catalysis. Meanwhile, the regulatory strategies, methods, and process control of the microbial synthesis of NMN are also elaborated, and the synthesis efficiencies of different chassis cells are systematically compared. Finally, this review summarizes the existing problems and challenges of microbial synthesis of NMN and proposes future strategies and directions to address these issues. This work provides technical references and a theoretical basis for researching efficient NMN microbial synthesis and application.