title: Network context and selection in the evolution to enzyme specificity.
abstract: 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 and 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.
authors.affiliation: Department of Bioengineering, University of California San Diego, La Jolla, CA 92093-0412, USA.
authors.forename: Hojung
authors.initials: H
authors.lastname: Nam
authors.forename: Nathan E
authors.initials: NE
authors.lastname: Lewis
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Lerman
authors.forename: Dae-Hee
authors.initials: DH
authors.lastname: Lee
authors.forename: Roger L
authors.initials: RL
authors.lastname: Chang
authors.forename: Donghyuk
authors.initials: D
authors.lastname: Kim
authors.forename: Bernhard O
authors.initials: BO
authors.lastname: Palsson
mesh_terms: D002384:Catalysis; D019295:Computational Biology; D004798:Enzymes / Q000235:genetics* / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D019143:Evolution, Molecular; D053858:Metabolic Networks and Pathways; D012641:Selection, Genetic; D013379:Substrate Specificity
chemical_list: D004798:Enzymes