Specific growth rate regulation in a simulated fed-batch E. coli fermentation

• Autor(a) principal: Rocha, I.
• Data de Publicação: 2006
• Outros Autores: Ferreira, Eugénio C.
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: https://hdl.handle.net/1822/5581
• topic: Specific growth rate estimators; Biomass observers; Asymptotic Observer; Fed-batch fermentation; E. coli; Specific growth rate control; Feedback-feedforward controller

The specific growth rate is one of the most important process variables characterizing the state of microorganisms during fermentations mainly because the biosynthesis of many products of interest is often related with the values assumed by this parameter. In the particular case of the fed-batch operation of Escherichia coli for the production of recombinant proteins, it is often argued that both pre- and the post-induction specific growth rates should be closely controlled in order to achieve maximum productivities on the desired recombinant protein. In this work a feedforward-feedback controller was developed with the purpose of regulating the global specific growth rate during a fed-batch fermentation of E. coli. The developed algorithm allows to maintain the cells in two different metabolic regimens (simultaneous oxidative and fermentative growth on glucose or oxidative growth on glucose), depending on the selected setpoint for the controlled variable. The pure open-loop version of the controller revealed a relatively poor performance when dealing with process noise. However, the introduction of on-line measurements of fermenter weight and biomass estimation obtained from asymptotic observers allowed a better approximation between the desired setpoints and the simulated values of the specific growth rates. Finally, the introduction of a proportional action in the controller equation allows an improved robustness against variations in model parameters.