TY - JOUR
T1 - Structural and functional analyses of microbial metabolic networks reveal novel insights into genome-scale metabolic fluxes
AU - Li, Gaoyang
AU - Cao, Huansheng
AU - Xu, Ying
N1 - Funding Information:
This work was supported by the US Department of Energy BioEnergy Science Center (grant number DE-PS02-06ER64304).
Publisher Copyright:
© 2018 The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
PY - 2018/3/27
Y1 - 2018/3/27
N2 - We present here an integrated analysis of structures and functions of genome-scale metabolic networks of 17 microorganisms. Our structural analyses of these networks revealed that the node degree of each network, represented as a (simplified) reaction network, follows a power-law distribution, and the clustering coefficient of each network has a positive correlation with the corresponding node degree. Together, these properties imply that each network has exactly one large and densely connected subnetwork or core. Further analyses revealed that each network consists of three functionally distinct subnetworks: (i) a core, consisting of a large number of directed reaction cycles of enzymes for interconversions among intermediate metabolites; (ii) a catabolic module, with a largely layered structure consisting of mostly catabolic enzymes; (iii) an anabolic module with a similar structure consisting of virtually all anabolic genes; and (iv) the three subnetworks cover on average ∼56, ∼31 and ∼13% of a network's nodes across the 17 networks, respectively. Functional analyses suggest: (1) cellular metabolic fluxes generally go from the catabolic module to the core for substantial interconversions, then the flux directions to anabolic module appear to be determined by input nutrient levels as well as a set of precursors needed for macromolecule syntheses; and (2) enzymes in each subnetwork have characteristic ranges of kinetic parameters, suggesting optimized metabolic and regulatory relationships among the three subnetworks.
AB - We present here an integrated analysis of structures and functions of genome-scale metabolic networks of 17 microorganisms. Our structural analyses of these networks revealed that the node degree of each network, represented as a (simplified) reaction network, follows a power-law distribution, and the clustering coefficient of each network has a positive correlation with the corresponding node degree. Together, these properties imply that each network has exactly one large and densely connected subnetwork or core. Further analyses revealed that each network consists of three functionally distinct subnetworks: (i) a core, consisting of a large number of directed reaction cycles of enzymes for interconversions among intermediate metabolites; (ii) a catabolic module, with a largely layered structure consisting of mostly catabolic enzymes; (iii) an anabolic module with a similar structure consisting of virtually all anabolic genes; and (iv) the three subnetworks cover on average ∼56, ∼31 and ∼13% of a network's nodes across the 17 networks, respectively. Functional analyses suggest: (1) cellular metabolic fluxes generally go from the catabolic module to the core for substantial interconversions, then the flux directions to anabolic module appear to be determined by input nutrient levels as well as a set of precursors needed for macromolecule syntheses; and (2) enzymes in each subnetwork have characteristic ranges of kinetic parameters, suggesting optimized metabolic and regulatory relationships among the three subnetworks.
KW - clustering coefficient distribution
KW - flux balance analysis
KW - functional modularity
KW - metabolic network
KW - network organizing principle
KW - scale-free network
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U2 - 10.1093/bib/bby022
DO - 10.1093/bib/bby022
M3 - Article
C2 - 29596572
AN - SCOPUS:85060995973
SN - 1467-5463
VL - 20
SP - 1590
EP - 1603
JO - Briefings in bioinformatics
JF - Briefings in bioinformatics
IS - 4
ER -