Transcriptome-guided engineering of a native niacin transporter in Lactiplantibacillus plantarum unveils metabolic rewiring for NMN biosynthesis

作者：Linghui Kong, Xinyu Li, Qing‐Yu He, Qingshou Yao, Lianzhong Ai, Jiayang Qin · 发表于：Frontiers in Microbiology · 年份：2025 · DOI：10.3389/fmicb.2025.1637666 · 被引用次数：4 · 研究领域：Probiotics and Fermented Foods、Microbial Metabolites in Food Biotechnology、Biochemical Analysis and Sensing Techniques

Introduction 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 . Methods A putative niacin transporter, lp2514 , was identified via molecular docking and validated by CRISPR/Cas9. A dual-copy expression strategy was also employed to increase NMN production. In parallel, RNA-seq was used to analyze genome-wide transcriptional changes associated with enhanced NMN biosynthesis. Results 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. Discussion This combined transporter engineering and transcriptome-guided strategy establishes a food-grade L. plantarum platform for efficient NMN production in functional fermented foods.