2013/04/29 by Avi I. Flamholz, Εlad Noor, Arren Bar‐Even +2 · 1 voice · 4 citations
Biochemistry, Genetics and Molecular Biology · #Bioinformatics and Genomic Networks #Microbial Metabolic Engineering and Bioproduction #Protein Structure and Dynamics
paper · pdf · doi:10.1073/pnas.1215283110
openalex publication_date 2013/04/29 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31
Contrary to the textbook portrayal of glycolysis as a single pathway conserved across all domains of life, not all sugar-consuming organisms use the canonical Embden-Meyerhoff-Parnass (EMP) glycolytic pathway. Prokaryotic glucose metabolism is particularly diverse, including several alternative glycolytic pathways, the most common of which is the Entner-Doudoroff (ED) pathway. The prevalence of the ED pathway is puzzling as it produces only one ATP per glucose--half as much as the EMP pathway. We argue that the diversity of prokaryotic glucose metabolism may reflect a tradeoff between a pathway's energy (ATP) yield and the amount of enzymatic protein required to catalyze pathway flux. We introduce methods for analyzing pathways in terms of thermodynamics and kinetics and show that the ED pathway is expected to require several-fold less enzymatic protein to achieve the same glucose conversion rate as the EMP pathway. Through genomic analysis, we further show that prokaryotes use different glycolytic pathways depending on their energy supply. Specifically, energy-deprived anaerobes overwhelmingly rely upon the higher ATP yield of the EMP pathway, whereas the ED pathway is common among facultative anaerobes and even more common among aerobes. In addition to demonstrating how protein costs can explain the use of alternative metabolic strategies, this study illustrates a direct connection between an organism's environment and the thermodynamic and biochemical properties of the metabolic pathways it employs.