{"title":"Establishing a novel pathway for the biosynthesis of nicotinamide mononucleotide.","authors":"Rongchen Feng, Ziting Yan, Guoguang Wei, Chaoqiang Wu, Feifei Chen, Alei Zhang, Sheng Xu, Xin Wang, Kequan Chen","doi":"10.1016/j.enzmictec.2025.110633","DOIUrl":null,"url":null,"abstract":"<p><p>Nicotinamide mononucleotide (NMN) is a pivotal molecule within the realm of metabolic health, serving as a precursor to nicotinamide adenine dinucleotide (NAD<sup>+</sup>), a critical coenzyme in cellular energy metabolism. In recent years, the biological production of NMN has garnered significant interest. In this study, we developed the novel NRK-dependent synthesis routes for NMN production. Two strategies were designed to supply D-ribose-1-phosphate (R-1-P): (1) phosphorylation of exogenous D-ribose to ribose-5-phosphate (R-5-P) using engineered ribokinase (RK), followed by isomerization to R-1-P; (2) R-5-P synthesis from glucose through the pentose phosphate pathway. An optimized in vitro multi-enzyme cascade (XapA/PNP/NRK, PPM, NRK) identified NRK as the most efficient catalyst for NMN biosynthesis from D-ribose and niacinamide. In Escherichia coli, overexpression of this cascade, knockout of competing pathways, and secretion enhancement via a pelB signal peptide-fused PnuC transporter achieved an NMN titer of 62.0 mg L<sup>-</sup>¹ .This work provides a viable alternative for the biosynthesis of NMN.</p>","PeriodicalId":11770,"journal":{"name":"Enzyme and Microbial Technology","volume":" ","pages":"110633"},"PeriodicalIF":3.4000,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Enzyme and Microbial Technology","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1016/j.enzmictec.2025.110633","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Nicotinamide mononucleotide (NMN) is a pivotal molecule within the realm of metabolic health, serving as a precursor to nicotinamide adenine dinucleotide (NAD+), a critical coenzyme in cellular energy metabolism. In recent years, the biological production of NMN has garnered significant interest. In this study, we developed the novel NRK-dependent synthesis routes for NMN production. Two strategies were designed to supply D-ribose-1-phosphate (R-1-P): (1) phosphorylation of exogenous D-ribose to ribose-5-phosphate (R-5-P) using engineered ribokinase (RK), followed by isomerization to R-1-P; (2) R-5-P synthesis from glucose through the pentose phosphate pathway. An optimized in vitro multi-enzyme cascade (XapA/PNP/NRK, PPM, NRK) identified NRK as the most efficient catalyst for NMN biosynthesis from D-ribose and niacinamide. In Escherichia coli, overexpression of this cascade, knockout of competing pathways, and secretion enhancement via a pelB signal peptide-fused PnuC transporter achieved an NMN titer of 62.0 mg L-¹ .This work provides a viable alternative for the biosynthesis of NMN.
期刊介绍:
Enzyme and Microbial Technology is an international, peer-reviewed journal publishing original research and reviews, of biotechnological significance and novelty, on basic and applied aspects of the science and technology of processes involving the use of enzymes, micro-organisms, animal cells and plant cells.
We especially encourage submissions on:
Biocatalysis and the use of Directed Evolution in Synthetic Biology and Biotechnology
Biotechnological Production of New Bioactive Molecules, Biomaterials, Biopharmaceuticals, and Biofuels
New Imaging Techniques and Biosensors, especially as applicable to Healthcare and Systems Biology
New Biotechnological Approaches in Genomics, Proteomics and Metabolomics
Metabolic Engineering, Biomolecular Engineering and Nanobiotechnology
Manuscripts which report isolation, purification, immobilization or utilization of organisms or enzymes which are already well-described in the literature are not suitable for publication in EMT, unless their primary purpose is to report significant new findings or approaches which are of broad biotechnological importance. Similarly, manuscripts which report optimization studies on well-established processes are inappropriate. EMT does not accept papers dealing with mathematical modeling unless they report significant, new experimental data.