(675a) Investigating Cellular Physiology of a Marine Cyanobacterium Using a Multi-Scale Multi-Paradigm Metabolic Model

Engineers have long used mathematical models as a way to simulate processes, identify bottlenecks or inefficiencies and improve designs. Metabolic models, specifically stoichiometric constraint based models, have been applied to living cells in the same way and have drastically reduced strain development time. Although these models have shown utility in strain design efforts, they are limited in their use due to the way they are formulated; they can only predict fluxes for an average cell in a well-mixed population. Here, we will describe our efforts to build the next generation of metabolic models which can track cells in time and space and account for difference in nutrient availability due to diffusion. We have embedded the genome-scale metabolic model of Trichodesmium erythraeum, a nitrogen fixing cyanobacterium, into an agent based modeling framework and allowed each cell to act independently. T. erythraeum was chosen as our model organism for this project due to the unique metabolism it has to allow nitrogen fixation and carbon fixation to occur simultaneously in the same filament. It is also integral to the global nitrogen cycle as it is responsible for reducing approximately 40% of all biologically fixed nitrogen and leaking up to half of it to provide a source of nitrogen for surrounding organisms. Using this model, we can not only predict behavior that is validated by in situ data, but we can also change rules of behavior and simulate emergent behavior to allow us to determine cellular objective and what rules the organism lives by. We will present our simulation results showing how we can track the concentration of nutrients and cells in time and space as well as how individual cells respond to these changing conditions by altering their metabolic fluxes. We will also discuss how we have used the model to investigate the physiology of the cell.