Network Context and Selection in the Evolution to Enzyme Specificity
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,...
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Published in | Science (American Association for the Advancement of Science) Vol. 337; no. 6098; pp. 1101 - 1104 |
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Main Authors | , , , , , , |
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 | |
Online Access | Get full text |
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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 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. |
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AbstractList | 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. 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. 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. Good Enough Can Be Good Enough To begin to understand why some enzymes are promiscuous and have many substrates, whereas others are highly specific, and why some have high activity, whereas others appear not to be optimized, Nam et al. (p. 1101 ) analyzed metabolic networks in bacteria. Specialist enzymes are essential for life, catalyze a high flux of enzymatic activity, and are more highly regulated. However, not all enzymes appear to be on a track of gradual improvement of specificity and efficiency. Generalist enzymes seem to well serve their own purposes, and their optimization may not justify the evolutionary cost. Are less promiscuous enzymes more highly evolved? 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. To begin to understand why some enzymes are promiscuous and have many substrates, whereas others are highly specific, and why some have high activity, whereas others appear not to be optimized, Nam et al. (p. 1101) analyzed metabolic networks in bacteria. Specialist enzymes are essential for life, catalyze a high flux of enzymatic activity, and are more highly regulated. However, not all enzymes appear to be on a track of gradual improvement of specificity and efficiency. Generalist enzymes seem to well serve their own purposes, and their optimization may not justify the evolutionary cost. [PUBLICATION 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. [PUBLICATION ABSTRACT] |
Author | Lerman, Joshua A. Nam, Hojung Lewis, Nathan E. Chang, Roger L. Kim, Donghyuk Palsson, Bernhard O. Lee, Dae-Hee |
AuthorAffiliation | 1 Department of Bioengineering, University of California San Diego, La Jolla, CA, 92093-0412, USA 2 Bioinformatics and Systems Biology Graduate Program, University of California San Diego, La Jolla, CA, 92093-0412, USA 3 Wyss Institute for Biologically Inspired Engineering and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA |
AuthorAffiliation_xml | – name: 2 Bioinformatics and Systems Biology Graduate Program, University of California San Diego, La Jolla, CA, 92093-0412, USA – name: 3 Wyss Institute for Biologically Inspired Engineering and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA – name: 1 Department of Bioengineering, University of California San Diego, La Jolla, CA, 92093-0412, USA |
Author_xml | – sequence: 1 givenname: Hojung surname: Nam fullname: Nam, Hojung – sequence: 2 givenname: Nathan E. surname: Lewis fullname: Lewis, Nathan E. – sequence: 3 givenname: Joshua A. surname: Lerman fullname: Lerman, Joshua A. – sequence: 4 givenname: Dae-Hee surname: Lee fullname: Lee, Dae-Hee – sequence: 5 givenname: Roger L. surname: Chang fullname: Chang, Roger L. – sequence: 6 givenname: Donghyuk surname: Kim fullname: Kim, Donghyuk – sequence: 7 givenname: Bernhard O. surname: Palsson fullname: Palsson, Bernhard O. |
BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26369425$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/22936779$$D View this record in MEDLINE/PubMed |
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Keywords | Molecular evolution Specificity Enzyme Escherichia coli Selection Bacteria Metabolism Gram negative bacteria Enterobacteriaceae |
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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Current address: Systems and Synthetic Biology Research Center. Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Korea The first two authors contributed equally. |
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Snippet | Enzymes are thought to have evolved highly specific catalytic activities from promiscuous ancestral proteins. By analyzing a genome-scale model of Escherichia... Good Enough Can Be Good Enough To begin to understand why some enzymes are promiscuous and have many substrates, whereas others are highly specific, and why... To begin to understand why some enzymes are promiscuous and have many substrates, whereas others are highly specific, and why some have high activity, whereas... Enzymes are thought to have evolved highly specific catalytic activities from promiscuous ancestral proteins. By analyzing a genome-scale model of Escherichia... |
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SubjectTerms | 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 |
Title | Network Context and Selection in the Evolution to Enzyme Specificity |
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