Effects of dual deletion of glnR and mtrA on expression of nitrogen metabolism genes in Streptomyces venezuelae

GlnR activates nitrogen metabolism genes under nitrogen‐limited conditions, whereas MtrA represses these genes under nutrient‐rich conditions in Streptomyces. In this study, we compared the transcription patterns of nitrogen metabolism genes in a double deletion mutant (ΔmtrA‐glnR) lacking both mtrA and glnR and in mutants lacking either mtrA (ΔmtrA) or glnR (ΔglnR). The nitrogen metabolism genes were expressed similarly in ΔmtrA‐glnR and ΔglnR under both nitrogen‐limited and nutrient‐rich conditions, with patterns distinctly different from that of ΔmtrA, suggesting a decisive role for GlnR in the control of nitrogen metabolism genes and further suggesting that regulation of these genes by MtrA is GlnR‐dependent. MtrA and GlnR utilize the same binding sites upstream of nitrogen metabolism genes, and we showed stronger in vivo binding of MtrA to these sites under nutrient‐rich conditions and of GlnR under nitrogen‐limited conditions, consistent with the higher levels of MtrA or GlnR under those respective conditions. In addition, we showed that both mtrA and glnR are self‐regulated. Our study provides new insights into the regulation of nitrogen metabolism genes in Streptomyces.