title: Simulation and prediction of protein production in fed-batch E. coli cultures: An engineering approach.
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.
authors.affiliation: Departament d'Enginyeria Química, Escola d'Enginyeria, Edifici Q, Universitat Autònoma de Barcelona, 08193 Bellaterra, Catalunya, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Calleja
authors.affiliation: School of Chemical and Biomolecular Engineering, Chemical Engineering Building, The University of Sydney, New South Wales, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Kavanagh
authors.affiliation: Departament d'Enginyeria Química, Escola d'Enginyeria, Edifici Q, Universitat Autònoma de Barcelona, 08193 Bellaterra, Catalunya, Spain.
authors.forename: Carles
authors.initials: C
authors.lastname: de Mas
authors.affiliation: Departament d'Enginyeria Química, Escola d'Enginyeria, Edifici Q, Universitat Autònoma de Barcelona, 08193 Bellaterra, Catalunya, Spain. josep.lopez@uab.cat.
authors.forename: Josep
authors.initials: J
authors.lastname: López-Santín
mesh_terms: D000446:Aldehyde-Lyases / Q000096:biosynthesis; D018533:Biomass; D004926:Escherichia coli / Q000254:growth & development* / Q000378:metabolism*; D008962:Models, Theoretical; D011994:Recombinant Proteins / Q000096:biosynthesis*; D013997:Time Factors; D015533:Transcriptional Activation
chemical_list: D011994:Recombinant Proteins; D000446:Aldehyde-Lyases; C022526:rhamnulose-1-phosphate adolase
keywords: E.coli; aldolases; fed-batch; protein production; simulation and modelling; transaminases