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Bioinformatics Advance Access published online on March 7, 2007
Bioinformatics, doi:10.1093/bioinformatics/btm082
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© The Author (2007). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Metabolic systems cost-benefit analysis for interpreting network structure and regulation

Ross P. Carlson *

Department of Chemical and Biological Engineering, Center for Biofilm Engineering, Montana State University, Bozeman, MT 59717, USA .

*To whom correspondence should be addressed. Dr. Ross Carlson, E-mail: rossc{at}erc.montana.edu


  Abstract

Motivation: Interpretation of bioinformatics data in terms of cellular function is a major challenge facing systems biology. This question is complicated by robust metabolic networks filled with structural features like parallel pathways and isozymes. Under conditions of nutrient sufficiency, metabolic networks are well known to be regulated for thermodynamic efficiency however; efficient biochemical pathways are anabolically expensive to construct. While parameters like thermodynamic efficiency have been extensively studied, a systems-based analysis of anabolic proteome synthesis ‘costs’ and the cellular function implications of these costs has not been reported.

Results: A cost-benefit analysis of an in silico Escherichia coli network revealed the relationship between metabolic pathway proteome synthesis requirements, DNA coding sequence length, thermodynamic efficiency and substrate affinity. The results highlight basic metabolic network design principles. Pathway proteome synthesis requirements appear to have shaped biochemical network structure and regulation. Under conditions of nutrient scarcity and other general stresses, E. coli expresses pathways with relatively inexpensive proteome synthesis requirements instead of more efficient but also anabolically more expensive pathways. This evolutionary strategy provides a cellular function-based explanation for common network motifs like isozymes and parallel pathways and possibly explains ‘overflow’ metabolisms observed during nutrient scarcity.

Supplementary information: accompanies this manuscript on the publisher’s web site

Associate Editor: Dr. Limsoon Wong

Received on November 2, 2006; revised on February 27, 2007; accepted on February 27, 2007

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