Comparison of Resilience against Genetic Perturbations in Microbial Metabolism

Abstract

In metabolic networks, microorganisms are able to survive genetic and environmental perturbations by redirecting the flux from one pathway to another. Hence, it is important to understand how design principles of metabolic networks confer this resilience to the organism. We used Flux Balance Analysis (FBA) and Minimization of Metabolic Adjustment (MOMA) in order to map the lethal gene deletions of two genome scale models of microbial metabolism - E. coli iAF1260 under aerobic growth and Synechocystis PCC6803 under heterotrophic and autotrophic growth - onto each other. Remarkably more than 50% of cyanobacterial lethal knockouts were non-lethal in bacteria. Comparisons of the pathways involved identifying some key subsystems of the bacterial metabolism and the electron flow machinery of cyanobacteria as being primarily responsible for conferring this resilience. We also used FBA to study epistasis in the cyanobacterial network, i.e. aggravating or buffering co-operativity in double gene deletions as compared to corresponding pair of single deletions. In accordance with previous results, heterotrophic and aerobic bacterial metabolism had both aggravating and buffering interactions between genes. Surprisingly however the autotrophic environment displayed a dominance of aggravating interactions with monochromatic interactions between subsystems. We also found that epistasis in an autotrophic organism was highly sensitive to light conditions, and under high light all interactions were aggravating. Our results suggest that the cyanobacterial metabolism is less resilient against genetic perturbations as compared to E. Coli, possibly due to greater specialization under autotrophic conditions.