biostudies-literatureUnknown10Sobala MNarodowe Centrum NaukiNational Institutes of HealthIn bacteria, the so-called stringent response is responsible for adaptation to changing environmental conditions. This response is mediated by guanosine derivatives [(p)ppGpp], synthesized by either large mono-functional RelA or bi-functional SpoT (synthesis and hydrolysis) enzymes in β- and γ-proteobacteria, such as Escherichia coli. In Firmicutes and α-, δ-, and 𝜀-proteobacteria, large bifunctional Rel-SpoT-homologs (RSH), often accompanied by small (p)ppGpp synthetases and/or hydrolases devoid of regulatory domains, are responsible for (p)ppGpp turnover. Here, we report on surprising in vitro and in vivo properties of an RSH enzyme from Methylobacterium extorquens (RSHMex). We find that this enzyme possesses someFrontiers in microbiology859https://www.ebi.ac.uk/biostudies/studies/S-EPMC6491832biostudies-literatureMethylobacterium extorquens RSH Enzyme Synthesizes (p)ppGpp and pppApp in vitro and in vivo, and Leads to Discovery of pppApp Synthesis in Escherichia coli.PMC6491832Bruhn-Olszewska BSobala MCashel MPotrykus KfalseMethylobacterium extorquens RSH Enzyme Synthesizes (p)ppGpp and pppApp in vitro and in vivo, and Leads to Discovery of pppApp Synthesis in Escherichia coli.In bacteria, the so-called stringent response is responsible for adaptation to changing environmental conditions. This response is mediated by guanosine derivatives [(p)ppGpp], synthesized by either large mono-functional RelA or bi-functional SpoT (synthesis and hydrolysis) enzymes in β- and γ-proteobacteria, such as Escherichia coli. In Firmicutes and α-, δ-, and 𝜀-proteobacteria, large bifunctional Rel-SpoT-homologs (RSH), often accompanied by small (p)ppGpp synthetases and/or hydrolases devoid of regulatory domains, are responsible for (p)ppGpp turnover. Here, we report on surprising in vitro and in vivo properties of an RSH enzyme from Methylobacterium extorquens (RSHMex). We find that this enzyme possesses some2019-01-01T00:00:00Z20192026-05-05T03:31:45.966Z2025-05-29T20:25:32.229ZS-EPMC64918323106892210.3389/fmicb.2019.00859