Deciphering mechanisms of stress-induced metabolic shifts in Corynebacterium glutamicum by transcriptomics and...

Corynebacterium glutamicum is a cornerstone amino acid microbial cell factory, yet its fermentation performance is impaired by thermal and hyperosmotic stresses. This study integrated transcriptomics with genome-scale metabolic modeling to dissect stress responses. Following 8-h exposure, high temperature significantly altered 1,294 genes, repressing central metabolism, ribosomal biogenesis, and transport, while activating thermal and oxidative stress responses. High-level sodium chloride (NaCl) or lysine sulphate (Lys-SO₄) differentially regulated 289 or 349 genes, respectively; NaCl promoted carbon metabolism and nutrient uptake, whereas Lys-SO₄ selectively activated sulphur metabolism. Transcriptomics-constrained metabolic modeling revealed that thermal or Lys-SO₄ stress commonly suppressed tricarboxylic acid cycle and respiration while increasing flux over pentose phosphate pathway and l-glutamate secretion, whereas NaCl stress induced acetate overflow. Model-guided prediction and experimental validation showed that overexpressing mez, panC, sucC, or sucD would enhance osmotolerance. Together, this framework resolves stressor-specific metabolic reprogramming in C. glutamicum and provides effective approach for engineering strain robustness.