High-concentration Mg2+ stress improves L-lactic acid biosynthesis of Bacillus coagulans revealed by combined analysis of transcriptome and metabolome

The application of magnesium oxide as a neutralizing agent significantly enhanced L-lactic acid (L-LA) production in Bacillus coagulans (B. coagulans), increasing titer, yield, productivity, and cell viability by 21.81 %, 7.61 %, 22.22 %, and 18.50 times, respectively. To elucidate the metabolic response to high-concentration Mg²⁺ stress, transcriptomic analysis identified 1021 differentially expressed genes (DEGs), with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealing predominant biological processes and pathway dysregulation. Metabolomic profiling detected 1196 differential metabolites, of which 216 were annotated to 129 metabolic pathways. Integrated multi-omics analyses delineated 10 core pathways involving 139 DEGs and 29 metabolites, demonstrating that Mg²⁺ stress enhances lactic acid fermentation efficiency through reprogramming of carbon flux, nucleic acid biosynthesis, amino acid metabolism, cofactor dynamics, membrane transport, and transcriptional regulation. This study provides mechanistic insights into B. coagulans adaptation to Mg²⁺ stress and proposes a viable strategy to optimize industrial L-LA bioproduction.