Network context and selection in the evolution to enzyme specificity

Hojung Nam, Nathan E. Lewis, Joshua A. Lerman, Dae Hee Lee, Roger L. Chang, Donghyuk Kim, Bernhard O. Palsson

Research output: Contribution to journalArticlepeer-review

203 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1101-1104
Number of pages4
JournalScience
Volume337
Issue number6098
DOIs
StatePublished - Aug 31 2012
Externally publishedYes

ASJC Scopus subject areas

  • General

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