Modeling the Metabolism of Escherichia coli Under Oxygen Gradients With Dynamically Changing Flux Bounds

摘要

In bioindustrial large scale fermenters microorganisms are exposed to conditions of unsteady nutrient supply which occur only rarely on small lab-scale fermenters and lead to economic losses. In aerobic processes cells face different availabilities of oxygen, nitrogen and carbon sources along various directions inside a fermenter. The adaptation of the central metabolism in the facultative anaerobic bacterium Escherichia coli to changing oxygen concentrations will be investigated. Flux balance analysis (FBA) is an often used method to calculate reaction fluxes under given environmental conditions. FBA is based on a stoichiometric model with possible reaction fluxes which are limited by constraints. One sort of constraints are the lower and upper flux bounds. Existing methods of FBA describe metabolic adaptations to changing environments not in sufficient detail. This work develops a variant of FBA in order to close this gap. Balance equations for important gene transcripts and gene products are formulated and flux bounds are calculated continuously. The described variant of FBA is applied to a model of E. coli central metabolism. A transition between anaerobic and aerobic environment is simulated. The results are compared with a conventional FBA approach and regulatory FBA (rFBA). The FBA method described in this study shows possible targets for experimental validation.