ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Food Microbiology
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1637666
Transcriptome-Guided Engineering of a Native Niacin Transporter in Lactiplantibacillus plantarum Unveils Metabolic Rewiring for NMN Biosynthesis
Provisionally accepted
- 1School of Pharmacy, Binzhou Medical University, Yantai, China
- 2Shanghai Jiao Tong University, Shanghai, China
- 3University of Shanghai for Science and Technology, Shanghai, China
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β-Nicotinamide mononucleotide (NMN), a precursor of NAD⁺, holds promise as a functional food ingredient for mitigating age-related decline. This study enhanced NMN biosynthesis in probiotic Lactiplantibacillus plantarum by engineering nicotinamide (NAM) uptake system and analyzing transcriptional responses. A putative niacin transporter, lp2514, was identified via molecular docking and validated by CRISPR/Cas9. Overexpression of lp2514 increased NMN production by 62.3%, and a dual-copy strategy raised NMN titers to 203 µmol L -1 -269% increase compared to empty-vector control without NAM and the highest yield reported in lactic acid bacteria. Transcriptomic analysis revealed 598 differentially expressed genes, including upregulated ribosomal proteins (rpsJ, rplE) and NAD⁺ salvage enzymes (aspA), indicating enhanced translation and precursor flux. Deleting cinA, encoding a metabolic constraint, further boosted NMN levels, confirming transcriptomic predictions. This combined transporter engineering and transcriptome-guided strategy establishes a food-grade L. plantarum platform for efficient NMN production in functional fermented foods.
Keywords: Nicotinamide Mononucleotide, Niacin transporter, Multicopy engineering, Transcriptomic Analysis, CRISPR/Cas9, lactiplantibacillus plantarum
Received: 29 May 2025; Accepted: 25 Jun 2025.
Copyright: © 2025 Kong, Li, He, Yao, Ai and Qin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Linghui Kong, School of Pharmacy, Binzhou Medical University, Yantai, China
Jiayang Qin, School of Pharmacy, Binzhou Medical University, Yantai, China
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