Simulation and prediction of protein production in fed-batch E. coli cultures : an engineering approach
Calleja Martínez, Daniel (Universitat Autònoma de Barcelona. Departament d'Enginyeria Química, Biològica i Ambiental)
Kavanagh, John (The University of Sydney. School of Chemical and Biomolecular Engineering)
Mas i Rocabayera, Carles de (Universitat Autònoma de Barcelona. Departament d'Enginyeria Química, Biològica i Ambiental)
López Santín, Josep (Universitat Autònoma de Barcelona. Departament d'Enginyeria Química, Biològica i Ambiental)

Date:	2016
Abstract:	An overall model describing the dynamic behavior of fed-batch E. coli processes for protein production has been built, calibrated and validated. Using a macroscopic approach, the model consists of three interconnected blocks allowing simulation of biomass, inducer and protein concentration profiles with time. The model incorporates calculation of the extra and intracellular inducer concentration, as well as repressor-inducer dynamics leading to a successful prediction of the product concentration. The parameters of the model were estimated using experimental data of a rhamnulose-1-phosphate aldolase-producer strain, grown under a wide range of experimental conditions. After validation, the model has successfully predicted the behavior of different strains producing two different proteins: fructose-6-phosphate aldolase and ω-transaminase. In summary, the presented approach represents a powerful tool for E. coli production process simulation and control.
Grants:	Ministerio de Ciencia e Innovación CTQ2011-28398-CO2-01 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-452
Rights:	Tots els drets reservats.
Language:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Subject:	Simulation and modelling ; Protein production ; Fed-batch ; E.coli ; Aldolases ; Transaminases
Published in:	Biotechnology and bioengineering, Vol. 113, No. 4 (April 2016) , p. 772-782, ISSN 0006-3592

DOI: 10.1002/bit.25842

Postprint 24 p, 1.8 MB

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