Zhang Puyue, Ye Ziru, Tian Zhong, Liu Qing, Huang Yong
School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan, China.
Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
Synth Syst Biotechnol. 2025 Apr 12;10(3):959-972. doi: 10.1016/j.synbio.2025.04.005. eCollection 2025 Sep.
Nicotinamide mononucleotide (NMN) is a nucleotide of significant biological importance, found abundantly in various foods such as meat, fruits, and vegetables. Recently, its potential effects in delaying aging have attracted considerable attention. Although chemical synthesis methods are commonly employed, they do not align with green production standards. In contrast, the biosynthesis of NMN is both safer and more environmentally sustainable. In this review, we established a novel "substrate-pathway-enzymology" framework to analyze the research on NMN biosynthesis. First, we systematically trace four substrates (nicotinamide ribose, nicotinamide, niacin, and nicotinamide adenine dinucleotide) and their respective metabolic routes. Then, we thoroughly investigate key enzymes through structural biology and protein engineering approaches, and converge the fragmented research findings across pathways to construct a comprehensive NMN biosynthesis network, revealing intricate metabolic regulations and pathway interactions. Through comparative analysis, the most promising biosynthetic pathway and prospects are discussed. Additionally, this review also provides original perspectives for NMN industrial development.
烟酰胺单核苷酸（NMN）是一种具有重要生物学意义的核苷酸，在肉类、水果和蔬菜等各种食物中大量存在。最近，其在延缓衰老方面的潜在作用引起了相当大的关注。虽然化学合成方法是常用的，但它们不符合绿色生产标准。相比之下，NMN的生物合成既更安全又更具环境可持续性。在这篇综述中，我们建立了一个新颖的“底物-途径-酶学”框架来分析NMN生物合成的研究。首先，我们系统地追踪四种底物（烟酰胺核糖、烟酰胺、烟酸和烟酰胺腺嘌呤二核苷酸）及其各自的代谢途径。然后，我们通过结构生物学和蛋白质工程方法深入研究关键酶，并汇总跨途径的零散研究结果，构建一个全面的NMN生物合成网络，揭示复杂的代谢调控和途径相互作用。通过比较分析，讨论了最有前景的生物合成途径和前景。此外，本综述还为NMN产业发展提供了独到的见解。
