Persulfidation of cysteine controls CRP function in E. coli

cAMP receptor protein (CRP) plays an important role in transcriptional regulation in Escherichia coli. Here, we demonstrate that in addition to regulating carbon metabolism, CRP also modulates sulfur metabolism in E. coli. When cultured in M9s medium until glucose depletion, E. coli W3110 produced H₂S, whereas a crp knockout strain did not. We discovered that persulfidation at CRP's Cys179 enhances its specific binding and upregulates the expression of sulfur metabolism-related genes (e.g., tnaA, mstA), thereby affecting production of the signaling molecule H₂S. This suggests CRP can adjust gene expression in response to carbon-sulfur fluctuations under certain conditions. Bioinformatic analyses reveal CRP homologs are widespread among bacteria, implying that CRP's sulfur-sensing ability may be a general mechanism balancing carbon and sulfur metabolism.

The online version contains supplementary material available at 10.1007/s13205-025-04643-5.