Network Context and Selection in the Evolution to Enzyme Specificity

• Published in: Science (American Association for the Advancement of Science) Vol. 337; no. 6098; pp. 1101 - 1104
• Main Authors: Nam, Hojung, Lewis, Nathan E., Lerman, Joshua A., Lee, Dae-Hee, Chang, Roger L., Kim, Donghyuk, Palsson, Bernhard O.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 31.08.2012; The American Association for the Advancement of Science
• Subjects: Bacteria; Bacteriology; Biochemistry; Biological and medical sciences; Carbon; Catalysis; Chemistry; Computational Biology; Enzyme substrates; Enzymes; Enzymes - genetics; Enzymes - metabolism; Escherichia coli - enzymology; Escherichia coli - genetics; Evolution; Evolution, Molecular; Fundamental and applied biological sciences. Psychology; Gene expression regulation; Histograms; Metabolic Networks and Pathways; Metabolism; Metabolism. Enzymes; Microbiology; Modeling; Protein metabolism; rev genes; Selection, Genetic; Substrate Specificity; Molecular evolution; Specificity; Enzyme; Escherichia coli; Selection; Bacteria; Metabolism; Gram negative bacteria; Enterobacteriaceae
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1216861

Enzymes are thought to have evolved highly specific catalytic activities from promiscuous ancestral proteins. By analyzing a genome-scale model of Escherichia coli metabolism, we found that 37% of its enzymes act on a variety of substrates and catalyze 65% of the known metabolic reactions. However, it is not apparent why these generalist enzymes remain. Here, we show that there are marked differences between generalist enzymes anf specialist enzymes, known to catalyze a single chemical reaction on one particular substrate in vivo. Specialist enzymes (i) are frequently essential, (ii) maintain higher metabolic flux, and (iii) require more regulation of enzyme activity to control metabolic flux in dynamic environments than do generalist enzymes. Furthermore, these properties are conserved in Archaea and Eukarya. Thus, the metabolic network context and environmental conditions influence enzyme evolution toward high specificity.