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Modelling overflow metabolism in Escherichia coli by acetate cycling
Anane, Emmanuel; López Cárdenas, Diana Carolina; Neubauer, Peter; Cruz-Bournazou, Mariano Nicolas
A new set of mathematical equations describing overflow metabolism and acetate accumulation in E. coli cultivation is presented. The model is a significant improvement of already existing models in the literature, with modifications based on the more recent concept of acetate cycling in E. coli, as revealed by proteomic studies of overflow routes. This concept opens up new questions regarding the speed of response of the acetate production and its consumption mechanisms in E. coli. The model is formulated as a set of continuous differentiable equations, which significantly improves model tractability and facilitates the computation of dynamic sensitivities in all relevant stages of fermentation (batch, fed-batch, starvation). The model is fitted to data from a simple 2 L fed-batch cultivation of E. coli W3110 M, where twelve (12) out of the sixteen (16) parameters were exclusively identified with relative standard deviation less than 10%. The framework presented gives valuable insight into the acetate dilemma in industrial fermentation processes, and serves as a tool for the development, optimization and control of E. coli fermentation processes.
