Metabolic plasticity in synthetic lethal mutants: Viability at higher cost.

ABSTRACT: The most frequent form of pairwise synthetic lethality (SL) in metabolic networks is known as plasticity synthetic lethality. It occurs when the simultaneous inhibition of paired functional and silent metabolic reactions or genes is lethal, while the default of the functional partner is backed up by the activation of the silent one. Using computational techniques on bacterial genome-scale metabolic reconstructions, we found that the failure of the functional partner triggers a critical reorganization of fluxes to ensure viability in the mutant which not only affects the SL pair but a significant fraction of other interconnected reactions, forming what we call a SL cluster. Interestingly, SL clusters show a strong entanglement both in terms of reactions and genes. This strong overlap mitiga

SUBMITTER: Massucci FA 

PROVIDER: S-EPMC5806928 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature