Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, USA.
Nat Chem Biol. 2024 Mar;20(3):314-322. doi: 10.1038/s41589-023-01395-2. Epub 2023 Aug 3.
Glycolysis is a universal metabolic process that breaks down glucose to produce adenosine triphosphate (ATP) and biomass precursors. The Entner-Doudoroff (ED) pathway is a glycolytic pathway that parallels textbook glycolysis but yields half as much ATP. Accordingly, in organisms that possess both glycolytic pathways (for example, Escherichia coli), its raison d'être remains a mystery. In this study, we found that the ED pathway provides a selective advantage during growth acceleration. Upon carbon and nitrogen upshifts, E. coli accelerates growth faster with than without the ED pathway. Concurrent isotope tracing reveals that the ED pathway flux increases faster than that of textbook glycolysis. We attribute the fast response time of the ED pathway to its strong thermodynamic driving force and streamlining of glucose import. Intermittent nutrient supply manifests the evolutionary advantage of the parallel glycolysis; thus, the dynamic nature of an ostensibly redundant pathway's role in promoting rapid adaptation constitutes a metabolic design principle.
糖酵解是一种普遍的代谢过程，可将葡萄糖分解为三磷酸腺苷 (ATP) 和生物量前体。Entner-Doudoroff (ED) 途径是一种糖酵解途径，与教科书中的糖酵解途径平行，但产生的 ATP 量只有一半。因此，在同时具有两种糖酵解途径的生物体内（例如，大肠杆菌），其存在的原因仍然是一个谜。在这项研究中，我们发现 ED 途径在生长加速过程中提供了选择性优势。在碳氮供应增加时，大肠杆菌在有 ED 途径的情况下比没有 ED 途径时生长更快。同时进行的同位素示踪表明，ED 途径的通量比教科书中的糖酵解途径增加得更快。我们将 ED 途径的快速响应时间归因于其强大的热力学驱动力和简化的葡萄糖导入。间歇性营养供应体现了平行糖酵解的进化优势；因此，在促进快速适应方面，表面上冗余途径的作用的动态性质构成了代谢设计原则。
