Title
Essential Plasticity And Redundancy Of Metabolism Unveiled By Synthetic Lethality Analysis
Abstract
We unravel how functional plasticity and redundancy are essential mechanisms underlying the ability to survive of metabolic networks. We perform an exhaustive computational screening of synthetic lethal reaction pairs in Escherichia coli in a minimal medium and we find that synthetic lethal pairs divide in two different groups depending on whether the synthetic lethal interaction works as a backup or as a parallel use mechanism, the first corresponding to essential plasticity and the second to essential redundancy. In E. coli, the analysis of pathways entanglement through essential redundancy supports the view that synthetic lethality affects preferentially a single function or pathway. In contrast, essential plasticity, the dominant class, tends to be inter-pathway but strongly localized and unveils Cell Envelope Biosynthesis as an essential backup for Membrane Lipid Metabolism. When comparing E. coli and Mycoplasma pneumoniae, we find that the metabolic networks of the two organisms exhibit a large difference in the relative importance of plasticity and redundancy which is consistent with the conjecture that plasticity is a sophisticated mechanism that requires a complex organization. Finally, coessential reaction pairs are explored in different environmental conditions to uncover the interplay between the two mechanisms. We find that synthetic lethal interactions and their classification in plasticity and redundancy are basically insensitive to medium composition, and are highly conserved even when the environment is enriched with nonessential compounds or overconstrained to decrease maximum biomass formation.
Year
DOI
Venue
2014
10.1371/journal.pcbi.1003637
PLOS COMPUTATIONAL BIOLOGY
Keywords
Field
DocType
apoptosis,escherichia coli,lipid metabolism,signal transduction,computer simulation
Biology,Metabolic pathway,Cell membrane,Synthetic lethality,Redundancy (engineering),Signal transduction,Metabolism,Bioinformatics,Genetics,Escherichia coli,Plasticity
Journal
Volume
Issue
ISSN
10
5
1553-7358
Citations 
PageRank 
References 
4
0.55
3
Authors
3
Name
Order
Citations
PageRank
Oriol Güell140.55
Francesc Sagués282.15
M Ángeles Serrano325717.84