Metabolic Tug-of-War between Glycolysis and Translation Revealed by Biochemical Reconstitution.

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  • Additional Information
    • Source:
      Publisher: American Chemical Society Country of Publication: United States NLM ID: 101575075 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2161-5063 (Electronic) Linking ISSN: 21615063 NLM ISO Abbreviation: ACS Synth Biol Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, D.C. : American Chemical Society, c2012-
    • Subject Terms:
      Glycolysis* ; Adenosine Triphosphate*/metabolism ; Protein Biosynthesis*; NAD/metabolism ; Escherichia coli/metabolism ; Escherichia coli/genetics ; Adenosine Triphosphatases/metabolism ; Adenosine Triphosphatases/genetics
    • Abstract:
      Inside cells, various biological systems work cooperatively for homeostasis and self-replication. These systems do not work independently as they compete for shared elements like ATP and NADH. However, it has been believed that such competition is not a problem in codependent biological systems such as the energy-supplying glycolysis and the energy-consuming translation system. In this study, we biochemically reconstituted the coupling system of glycolysis and translation using purified elements and found that the competition for ATP between glycolysis and protein synthesis interferes with their coupling. Both experiments and simulations revealed that this interference is derived from a metabolic tug-of-war between glycolysis and translation based on their reaction rates, which changes the threshold of the initial substrate concentration for the success coupling. By the metabolic tug-of-war, translation energized by strong glycolysis is facilitated by an exogenous ATPase, which normally inhibits translation. These findings provide chemical insights into the mechanism of competition among biological systems in living cells and provide a framework for the construction of synthetic metabolism in vitro.
    • Contributed Indexing:
      Keywords: biochemical simulations; bottom-up synthetic biology; cell-free protein synthesis; glycolysis; resource allocation
    • Publication Date:
      Date Created: 20240508 Date Completed: 20240517 Latest Revision: 20240620
    • Publication Date:
      20240620
    • Accession Number:
      10.1021/acssynbio.4c00209
    • Accession Number:
      38717981