TY - JOUR
T1 - Network context and selection in the evolution to enzyme specificity
AU - Nam, Hojung
AU - Lewis, Nathan E.
AU - Lerman, Joshua A.
AU - Lee, Dae Hee
AU - Chang, Roger L.
AU - Kim, Donghyuk
AU - Palsson, Bernhard O.
N1 - Funding Information:
This research was funded by a doctoral research scheme (DRS) grant number ( 20.03/13/13.14/1 ) by the Universiti Malaysia Pahang and by the Eastern Unity Technology under grant number ( UIC190806 ).
PY - 2012/8/31
Y1 - 2012/8/31
N2 - 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.
AB - 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.
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U2 - 10.1126/science.1216861
DO - 10.1126/science.1216861
M3 - Article
AN - SCOPUS:84865571240
SN - 0036-8075
VL - 337
SP - 1101
EP - 1104
JO - Science
JF - Science
IS - 6098
ER -