biostudies-literatureFu YNational Natural Science Foundation of ChinaNational Key Research and Development Program of China6870-6882https://www.ebi.ac.uk/biostudies/studies/S-EPMC10359459biostudies-literatureUnknown51(13)Actinobacteria are ubiquitous bacteria undergoing complex developmental transitions coinciding with antibiotic production in response to stress or nutrient starvation. This transition is mainly controlled by the interaction between the second messenger c-di-GMP and the master repressor BldD. To date, the upstream factors and the global signal networks that regulate these intriguing cell biological processes remain unknown. In Saccharopolyspora erythraea, we found that acetyl phosphate (AcP) accumulation resulting from environmental nitrogen stress participated in the regulation of BldD activity through cooperation with c-di-GMP. AcP-induced acetylation of BldD at K11 caused the BldD dimer to fall apart and dissociate from the target DNA and disrupted the signal transduction of c-di-GMP, thNucleic acids researchA meet-up of acetyl phosphate and c-di-GMP modulates BldD activity for development and antibiotic production.PMC10359459317300042020YFA090910032070066Ye BCFu YYou DShen JLYin BCDong YQfalseA meet-up of acetyl phosphate and c-di-GMP modulates BldD activity for development and antibiotic production.Actinobacteria are ubiquitous bacteria undergoing complex developmental transitions coinciding with antibiotic production in response to stress or nutrient starvation. This transition is mainly controlled by the interaction between the second messenger c-di-GMP and the master repressor BldD. To date, the upstream factors and the global signal networks that regulate these intriguing cell biological processes remain unknown. In Saccharopolyspora erythraea, we found that acetyl phosphate (AcP) accumulation resulting from environmental nitrogen stress participated in the regulation of BldD activity through cooperation with c-di-GMP. AcP-induced acetylation of BldD at K11 caused the BldD dimer to fall apart and dissociate from the target DNA and disrupted the signal transduction of c-di-GMP, th2023-01-01T00:00:00Z2023 Jul2025-07-04T03:05:55.784Z2025-07-04T03:05:55.784ZS-EPMC103594593728305610.1093/nar/gkad494