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Paulina Katarzyna Grucela1, Tobias Fuhrer2, Uwe Sauer2, Yanjie Chao3 and Yong Everett Zhang1

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The bacterial stringent response and its effector alarmone guanosine penta- or tetra – phosphates (p)ppGpp are vital for bacterial tolerance and survival of various stresses in environments (including antibiotics) and host cells (virulence). (p)ppGpp does so by binding to its numerous target proteins and reprograming bacterial transcriptome to tune down the synthesis of nucleotides and rRNA/tRNA, and up-regulate amino acid biosynthesis genes. Recent identification of more novel (p)ppGpp direct binding proteins in Escherichia coli and their deep studies have unveiled unprecedented details of how (p)ppGpp coordinates the nucleotide and amino acid metabolic pathways upon stringent response; however, the mechanistic link between nucleotide and amino acid metabolisms remains still incompletely understood. Here we propose the metabolite ribose 5’-phosphate as the key link between nucleotide and amino acid metabolisms and a working model integrating both the transcriptional and metabolic effects of (p)ppGpp on E. coli physiological adaptation during the stringent response.

ACKNOWLEDGMENTS

This work is supported by National Key R&D Program of China (2022YFE0111800 to Y.C.), Novo Nordisk Foundation Project Grant (NNF19OC0058331 to Y.E.Z), Chinese Academy of Sci-ences (176002GJHZ2022022MI to Y.C.), Shanghai Munic-ipal Science and Technology Commission (21ZR1471300 to Y.C.).

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Ribose 5-phosphate: the key metabolite bridging the metabolisms of nucleotides and amino acids during stringent response in Escherichia coli? by Grucela et al. is licensed under a Creative Commons Attribution 4.0 International License.