Elementary Mode Analysis: A Useful Metabolic Pathway Analysis Tool for Reprograming Microbial Metabolic Pathways
Elementary mode analysis is a useful metabolic pathway analysis tool to characterize cellular metabolism. It can identify all feasible metabolic pathways known as elementary modes that are inherent to a metabolic network. Each elementary mode contains a m
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Elementary Mode Analysis: A Useful Metabolic Pathway Analysis Tool for Reprograming Microbial Metabolic Pathways Cong T. Trinh and R. Adam Thompson
Abstract Elementary mode analysis is a useful metabolic pathway analysis tool to characterize cellular metabolism. It can identify all feasible metabolic pathways known as elementary modes that are inherent to a metabolic network. Each elementary mode contains a minimal and unique set of enzymatic reactions that can support cellular functions at steady state. Knowledge of all these pathway options enables systematic characterization of cellular phenotypes, analysis of metabolic network properties (e.g. structure, regulation, robustness, and fragility), phenotypic behavior discovery, and rational strain design for metabolic engineering application. This chapter focuses on the application of elementary mode analysis to reprogram microbial metabolic pathways for rational strain design and the metabolic pathway evolution of designed strains. Keywords Elementary mode analysis • Engineering • Genetic knockout analysis • Metabolic minimal metabolic functionality • Rational strain design
Abbreviations CASOP cMCS
computational approach for strain optimization aiming at high productivity constrained minimal cut set
C.T. Trinh (*) Department of Chemical and Biomolecular Engineering, University of Tennessee, Knoxville, TN, USA e-mail: [email protected]. R.A. Thompson Bredesen Center for Interdisciplinary Research and Graduate Education, University of Tennessee, Knoxville, TN, USA X. Wang et al. (eds.), Reprogramming Microbial Metabolic Pathways, Subcellular Biochemistry 64, DOI 10.1007/978-94-007-5055-5_2, © Springer Science+Business Media Dordrecht 2012
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C.T. Trinh and R.A. Thompson
elementary mode elementary mode analysis extreme pathway flux balance analysis metabolic flux analysis metabolic pathway analysis
Introduction
Advances in sequencing technology have generated a large database of genome sequences of different organisms across the three kingdoms of bacteria, eukaryote, and archaea (Pagani et al. 2012). Based on these sequences, comparative genomics enable the automated reconstruction of drafted metabolic networks of these sequenced organisms in a high throughput manner (Henry et al. 2010). A standard protocol has been recently developed to curate these draft metabolic networks to improve the model accuracy (Thiele and Palsson 2010). A reconstructed metabolic network provides a useful link between cellular genotype and phenotype that enables a systematic analysis of cellular metabolism (Durot et al. 2009). Based on the first principle of mass conservation, different metabolic network analysis tools have been developed to predict the fates of metabolites and metabolic flux distributions that define cellular phenotypes under environmental and genetic perturbations (Lewis et al. 2012). A list of curated metabolic network models for some organisms suitable for metabolic network analysis can be found in the BiGG database (Schellenberg
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