(278e) Decomposing Complex Microbial Behaviors Using Cost-Benefit Analysis

Wide ranging, seemingly unrelated Escherichia coli physiological fluxes can be simply and accurately described as linear combinations of a few ecologically relevant stress adaptations. These strategies were identified by decomposing the central metabolism of E. coli into elementary modes (mathematically defined biochemical pathways) and assessing the resource investment cost-benefit properties for each pathway. The approach capitalizes on the inherent trade-offs related to investing finite resources like nitrogen into different pathway enzymes when the pathways have varying metabolic efficiencies. The subset of ecologically competitive pathways represented less than 0.02% of the total permissible pathways. These pathways were used to describe published 13C fluxome data. The accuracy and biological relevance of the assembled strategies were tested against 10,000 randomly constructed pathway subsets. None of the randomly assembled collections were able to describe all of the considered experimental data as accurately as the costs based subset suggesting these metabolic strategies are biologically significant. The current descriptions were compared with an extensive set of linear programming (LP) based flux descriptions using the Euclidean distance metric. The current study's pathway subset described the experimental fluxes with better accuracy and hints at the existence of new objective functions which could improve LP based metabolic flux descriptions. The assembled pathways seem to represent a generalized set of strategies that can describe a wide range of microbial responses and hint at evolutionary processes where a handful of successful metabolic strategies are utilized simultaneously in different combinations to adapt to diverse conditions.