Abstract:
Identification of limiting capacities in metabolism of a producer strain is currently not possible in biotechnological production processes. In this work, a new experimental approach was developed to separate micro-organisms during a bioprocess and analyse them in a bioreactor operated in parallel. In short-term experiments of several minutes metabolic disturbances are induced in the perturbation reactor and the biological response is captured quantitatively by metabolic flux and metablome analyses. Using kinetic modeling of intracellular metabolism and sensitivity analysis, the approach revealed for the first time the control structure of central metabolism of Escherichia coli under conditions of a fed-batch process.