Transcriptomics with metabolomics reveals the mechanism of alkaline tolerance in Halomonas alkalicola CICC 11012s

The potential of alkaline-tolerant bacteria as cell factories for the production of functional molecules and bulk chemicals has been increasingly recognized owing to in-depth studies of their metabolic pathways and products combined with their tolerance to alkaline environments. To further explore the cell factory potential of alkaline-tolerant bacteria, it is necessary to systematically analyze and explore the genes and metabolites related to alkaline tolerance. Halomonas alkalicola CICC 11012s is currently the strongest alkaliphile of the genus Halomonas, which can grow at pH 12.5. This study aimed to elucidate the molecular mechanisms underlying the response of H. alkalicola CICC 11012s to alkaline stress, using transcriptomic and metabolomic analyses. The expression of 259 genes and 401 metabolites was significantly altered. Important metabolic pathways included nucleotide, amino acid, and carbohydrate metabolism, as well as membrane transport. Furthermore, an integrative pathway analysis revealed that two pathways, glycine, serine, and threonine metabolism and biotin metabolism, were significantly enriched under high-alkaline conditions (pH 11.0). These findings highlight that deletion of the gene cluster tonB-exbB-exbB2-exbD significantly affects the synthesis of L-aspartate, leading to a decrease in the alkaline tolerance of H. alkalicola.