食品科学 ›› 2025, Vol. 46 ›› Issue (13): 18-24.doi: 10.7506/spkx1002-6630-20241127-183

• 植物化合物生物合成专栏 • 上一篇    

生物合成β-烟酰胺单核苷酸及其衍生物研究进展

王昭颖,郭新浩,黄馨禾,陈卓妍,刘岳琪,李娟,陈宁,范晓光   

  1. (1.天津科技大学 工业发酵微生物教育部重点实验室,天津 300457;2.天津博创合成生物科技有限公司,天津 300450)
  • 发布日期:2025-06-13
  • 基金资助:
    “十四五”国家重点研发计划重点专项(2022YFD2101401)

Review on Biosynthesis of β-Nicotinamide Mononucleotide and Its Derivatives

WANG Zhaoying, GUO Xinhao, HUANG Xinhe, CHEN Zhuoyan, LIU Yueqi, LI Juan, CHEN Ning, FAN Xiaoguang   

  1. (1. Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin University of Science and Technology, Tianjin 300457, China; 2. Tianjin Bochuang Synthetic Biotechnology Co. Ltd., Tianjin 300450, China)
  • Published:2025-06-13

摘要: β-烟酰胺单核苷酸(β-nicotinamide mononucleotide,NMN)存在于所有生物体中,作为治疗阿尔茨海默病、癌症、衰老和血管功能障碍等多种疾病的营养品和医药产品受到了广泛关注。化学合成法是NMN的主要生产方法,但存在合成路线繁琐、反应条件严苛、产物手性分离困难、有机溶剂使用等问题,导致产品价格昂贵、应用范围受限。相比之下,生物合成法因具有无毒性、加工条件温和、底物特异性高、产品选择性强、转化效率高等显著优势,已逐渐成为NMN生产的理想替代方案。NMN的生物合成主要以烟酰胺、烟酰胺核糖、烟酸或葡萄糖为起始原料,经不同的代谢途径产生,涉及的关键酶包括烟酰胺磷酸核糖基转移酶、烟酰胺核糖激酶和NMN合成酶等。本文重点介绍利用酶催化和发酵法生产NMN的最新研究进展,包括关键酶的选择和改良、酶级联催化反应设计、酶的固定化、细胞工厂构建以及发酵过程优化策略等。此外,介绍NMN衍生物烟酰胺核糖和烟酰胺腺嘌呤二核苷酸的生物合成技术。这些研究将为开发低成本、高效率的NMN及其衍生物的生产方法提供参考。

关键词: β-烟酰胺单核苷酸;烟酰胺核糖;烟酰胺腺嘌呤二核苷酸;生物合成

Abstract: β-Nicotinamide mononucleotide (NMN) is present in all organisms and has attracted widespread attention as a nutritional supplement and pharmaceutical product for the treatment of various diseases, such as Alzheimer’s disease, cancer, aging, and vascular dysfunction. Chemical synthesis is the major method for producing NMN, but it faces challenges such as complex synthesis routes, harsh reaction conditions, difficulties in chiral separation of products, and the use of organic solvents, resulting in high product price and limited applications. In contrast, biosynthesis, with its significant advantages of non-toxicity, mild processing conditions, high substrate specificity, strong product selectivity, and high conversion efficiency, has gradually become an ideal alternative for NMN production. NMN is biosynthesized mainly from niacinamide, nicotinamide riboside, niacin, or glucose through different metabolic pathways, and the key enzymes involved include nicotinamide phosphoribosyltransferase, nicotinamide riboside kinase, and NMN synthase. This article focuses on the latest progress in the enzymatic and microbial production of NMN, including the selection and modification of key enzymes, the design of enzymatic cascade reaction, the immobilization of enzymes, the construction of cell factories, and optimization strategies for the fermentation process. In addition, the biosynthesis technologies for NMN derivatives nicotinamide riboside (NR) and nicotinamide adenine dinucleotide (NAD+) are reviewed. These studies will provide references for the development of low-cost, high-efficiency methods for the production of NMN and its derivatives.

Key words: β-nicotinamide mononucleotide; nicotinamide riboside; nicotinamide adenine dinucleotide; biosynthesis

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