The Application of Adaptive Model Predictive Control for Fed-Batch <i>Escherichia coli</i> BL21 (DE3) Cultivation and Biosynthesis of Recombinant Proteins
Konstantins Dubencovs,
Arturs Suleiko,
Elina Sile,
Ivars Petrovskis,
Inara Akopjana,
Anastasija Suleiko,
Vytautas Galvanauskas,
Kaspars Tars,
Juris Vanags
Affiliations
Konstantins Dubencovs
Laboratory of Bioengineering, Latvian State Institute of Wood Chemistry, Dzerbenes Street 27, LV-1006 Riga, Latvia
Arturs Suleiko
Laboratory of Bioengineering, Latvian State Institute of Wood Chemistry, Dzerbenes Street 27, LV-1006 Riga, Latvia
Elina Sile
Institute of Applied Chemistry, Faculty of Materials Science and Applied Chemistry, Riga Technical University, Paula Valdena Street 3, LV-1048 Riga, Latvia
Ivars Petrovskis
Latvian Biomedical Research and Study Centre, Ratsupites Street 1, LV-1067 Riga, Latvia
Inara Akopjana
Latvian Biomedical Research and Study Centre, Ratsupites Street 1, LV-1067 Riga, Latvia
Anastasija Suleiko
Laboratory of Bioengineering, Latvian State Institute of Wood Chemistry, Dzerbenes Street 27, LV-1006 Riga, Latvia
Vytautas Galvanauskas
Department of Automation, Kaunas University of Technology, LT-51367 Kaunas, Lithuania
Kaspars Tars
Latvian Biomedical Research and Study Centre, Ratsupites Street 1, LV-1067 Riga, Latvia
Juris Vanags
Laboratory of Bioengineering, Latvian State Institute of Wood Chemistry, Dzerbenes Street 27, LV-1006 Riga, Latvia
A model predictive control (MPC) method was investigated as a route to optimize and control the growth of E. coli BL21 (DE3) and biosynthesis of two different recombinant proteins (nerve growth factor NGF and coat protein of bacteriophage Qβ (Qβ-CP)). To determine the target trajectory for the E. coli cultivation process and estimate the model parameters, the off-line run-to-run optimization method was used. The proven method allowed us to successfully control the growth of microbial biomass, with a deviation of 6–12% from the target trajectory. It was proven that it is possible to obtain a “Golden Batch” profile for the implementation of MPC using datasets from only four to eight fermentation runs. The method showed its robustness when the cultivation of E. coli was carried out with two different titrant supply control systems—volumetric and gravimetric. Furthermore, the MPC method exhibited high adaptability, reliability, and resistance to various types of disturbances. MPC proved to be a reliable and effective method for controlling the cultivation and recombinant protein biosynthesis of fast-growing microorganisms such as E. coli.
