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Simulation and prediction of protein production in fed‐batch E. coli cultures: An engineering approach
Author(s) -
Calleja Daniel,
Kavanagh John,
de Mas Carles,
LópezSantín Josep
Publication year - 2016
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.25842
Subject(s) - inducer , aldolase a , biological system , strain (injury) , biochemistry , chemistry , biology , enzyme , anatomy , gene
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. Biotechnol. Bioeng. 2016;113: 772–782. © 2015 Wiley Periodicals, Inc.