Network of nicotinamide mononucleotide biosynthesis: substrate tracking, rate-limiting enzyme, and regulatory strategy

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 em...

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Main Authors: Puyue Zhang, Ziru Ye, Zhong Tian, Qing Liu, Yong Huang
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-09-01
Series:Synthetic and Systems Biotechnology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405805X25000523
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author Puyue Zhang
Ziru Ye
Zhong Tian
Qing Liu
Yong Huang
author_facet Puyue Zhang
Ziru Ye
Zhong Tian
Qing Liu
Yong Huang
author_sort Puyue Zhang
collection DOAJ
description 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.
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publisher KeAi Communications Co., Ltd.
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series Synthetic and Systems Biotechnology
spelling doaj-art-97fe4425b0254280b9fcfb618f7dcbee2025-08-20T03:49:41ZengKeAi Communications Co., Ltd.Synthetic and Systems Biotechnology2405-805X2025-09-0110395997210.1016/j.synbio.2025.04.005Network of nicotinamide mononucleotide biosynthesis: substrate tracking, rate-limiting enzyme, and regulatory strategyPuyue Zhang0Ziru Ye1Zhong Tian2Qing Liu3Yong Huang4School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan, ChinaInnovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, ChinaSchool of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China; Corresponding author.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; Corresponding author. School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan, China.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.http://www.sciencedirect.com/science/article/pii/S2405805X25000523Nicotinamide mononucleotideBiosynthesisEnzymatic reactionsProtein engineeringStructural biology
spellingShingle Puyue Zhang
Ziru Ye
Zhong Tian
Qing Liu
Yong Huang
Network of nicotinamide mononucleotide biosynthesis: substrate tracking, rate-limiting enzyme, and regulatory strategy
Synthetic and Systems Biotechnology
Nicotinamide mononucleotide
Biosynthesis
Enzymatic reactions
Protein engineering
Structural biology
title Network of nicotinamide mononucleotide biosynthesis: substrate tracking, rate-limiting enzyme, and regulatory strategy
title_full Network of nicotinamide mononucleotide biosynthesis: substrate tracking, rate-limiting enzyme, and regulatory strategy
title_fullStr Network of nicotinamide mononucleotide biosynthesis: substrate tracking, rate-limiting enzyme, and regulatory strategy
title_full_unstemmed Network of nicotinamide mononucleotide biosynthesis: substrate tracking, rate-limiting enzyme, and regulatory strategy
title_short Network of nicotinamide mononucleotide biosynthesis: substrate tracking, rate-limiting enzyme, and regulatory strategy
title_sort network of nicotinamide mononucleotide biosynthesis substrate tracking rate limiting enzyme and regulatory strategy
topic Nicotinamide mononucleotide
Biosynthesis
Enzymatic reactions
Protein engineering
Structural biology
url http://www.sciencedirect.com/science/article/pii/S2405805X25000523
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