The ldhA Gene Encoding Fermentative l-Lactate Dehydrogenase in Corynebacterium Glutamicum Is Positively Regulated by the Global Regulator GlxR

Bacterial metabolism shifts from aerobic respiration to fermentation at the transition from exponential to stationary growth phases in response to limited oxygen availability. Corynebacterium glutamicum, a Gram-positive, facultative aerobic bacterium used for industrial amino acid production, excretes l-lactate, acetate, and succinate as fermentation products. The ldhA gene encoding l-lactate dehydrogenase is solely responsible for l-lactate production. Its expression is repressed at the exponential phase and prominently induced at the transition phase. ldhA is transcriptionally repressed by the sugar-phosphate-responsive regulator SugR and l-lactate-responsive regulator LldR. Although ldhA expression is derepressed even at the exponential phase in the sugR and lldR double deletion mutant, a further increase in its expression is still observed at the stationary phase, implicating the action of additional transcription regulators. In this study, involvement of the cAMP receptor protein-type global regulator GlxR in the regulation of ldhA expression was investigated. The GlxR-binding site found in the ldhA promoter was modified to inhibit or enhance binding of GlxR. The ldhA promoter activity and expression of ldhA were altered in proportion to the binding affinity of GlxR. Similarly, l-lactate production was also affected by the binding site modification. Thus, GlxR was demonstrated to act as a transcriptional activator of ldhA.

Automated summary

When transitioning from exponential to stationary growth phases, bacterial metabolism shifts from aerobic respiration to fermentation in response to limited oxygen availability. The ldhA gene in Corynebacterium glutamicum encodes l-lactate dehydrogenase, responsible for l-lactate production, and is controlled by transcription regulators SugR, LldR, and GlxR. GlxR has been shown to act as a transcriptional activator of ldhA, affecting both its promoter activity and l-lactate production.