Paper Info
Title
Metabolic Regulation Is Sufficient For Global And Robust Coordination Of Glucose Uptake, Catabolism, Energy Production And Growth In Escherichia Coli
Abstract
The metabolism of microorganisms is regulated through two main mechanisms: changes of enzyme capacities as a consequence of gene expression modulation ("hierarchical control") and changes of enzyme activities through metabolite-enzyme interactions. An increasing body of evidence indicates that hierarchical control is insufficient to explain metabolic behaviors, but the system-wide impact of metabolic regulation remains largely uncharacterized. To clarify its role, we developed and validated a detailed kinetic model of Escherichia coli central metabolism that links growth to environment. Metabolic control analyses confirm that the control is widely distributed across the network and highlight strong interconnections between all the pathways. Exploration of the model solution space reveals that several robust properties emerge from metabolic regulation, from the molecular level (e.g. homeostasis of total metabolite pool) to the overall cellular physiology (e.g. coordination of carbon uptake, catabolism, energy and redox production, and growth), while allowing a large degree of flexibility at most individual metabolic steps. These properties have important physiological implications for E. coli and significantly expand the self-regulating capacities of its metabolism.
Year
DOI
Venue
2017
10.1371/journal.pcbi.1005396
PLOS COMPUTATIONAL BIOLOGY
Field
DocType
Volume
Glucose uptake,Enzyme,Biology,Biochemistry,Metabolic flux analysis,Metabolic control analysis,Metabolism,Metabolite,Carbohydrate metabolism,Catabolism
Journal
13
Issue
ISSN
Citations 
2
1553-7358
4
PageRank 
References 
Authors
0.49
5
3
Name
Order
Citations
PageRank
Pierre Millard1133.05
Kieran Smallbone21429.16
Pedro Mendes364851.61