Biosynthesis of Nicotinamide Mononucleotide: Synthesis Method, Enzyme, and Biocatalytic System

Abstract

Nicotinamide mononucleotide (NMN) has garnered substantial interest as a functional food product. Industrial NMN production relies on chemical methods, facing challenges in separation, purification, and regulatory complexities, leading to elevated prices. In contrast, NMN biosynthesis through fermentation or enzyme catalysis offers notable benefits like eco-friendliness, recyclability, and efficiency, positioning it as a primary avenue for future NMN synthesis. Enzymatic NMN synthesis encompasses the nicotinamide-initial route and nicotinamide ribose-initial routes. Key among these is nicotinamide riboside kinase (NRK), pivotal in the latter route. The NRK-mediated biosynthesis is emerging as a prominent trend due to its streamlined route, simplicity, and precise specificity. The essential aspect is to obtain an engineered NRK that exhibits elevated activity and robust stability. This review comprehensively assesses diverse NMN synthesis methods, offering valuable insights into efficient, sustainable, and economical production routes. It spotlights the emerging NRK-mediated biosynthesis pathway and its significance. The establishment of an adenosine triphosphate (ATP) regeneration system plays a pivotal role in enhancing NMN synthesis efficiency through NRK-catalyzed routes. The review aims to be a reference for researchers developing green and sustainable NMN synthesis, as well as those optimizing NMN production.

Design of NAMPTs with Superior Activity by Dual-Channel Protein Engineering Strategy

“…This route involves a key enzyme, nicotinamide phosphoribosyltransferase (NAMPT), which catalyzed the substitution reactions involving substrates with large volume and multiple side chains, phosphoribosyl pyrophosphate (PRPP), and nicotinamide (NAM). However, the low activities of the natural NAMPTs and the inhibitory effect of byproducts pyrophosphoric acid (PPi) on enzyme activity have greatly hampered its industrial applications. − The main characteristic of the two main substrates toward NAMPT is large side chains with a circular structure. In addition, the activity of NAMPT is commonly suppressed by specific small-molecule compounds, and these inhibitory effects are intricately linked to the protein structure of the enzyme. , The byproduct PPi comprises two tetrahedral structures formed by phosphate groups, and it has a similar side-chain structure of the substrate, which may hinder the substrate from entering the enzyme active center.…”