Generic model control applied to E. coli BL21(DE3) fed-batch cultures

This work proposes a Generic Model Control (GMC) strategy to regulate biomass growth in fed-batch cultures of Escherichia coli BL21(DE3). The control law is established using a previously validated mechanistic model based on the overflow metabolism paradigm. A model reduction is carried out to prevent the controller from relying on kinetics, which may be uncertain. In order to limit the controller to the use of a single measurement, i.e., biomass concentration which is readily available, a Kalman filter is designed to reconstruct the nonmeasurable information from the outlet gas and the remaining stoichiometry. Several numerical simulations are presented to assess the controller robustness with respect to model uncertainty. Experimental validation of the proposed GMC strategy is achieved with a lab-scale bioreactor.

[1]  S. Lee,et al.  High cell-density culture of Escherichia coli. , 1996, Trends in biotechnology.

[2]  Laurent Dewasme,et al.  Experimental validation of an Extended Kalman Filter estimating acetate concentration in E. coli cultures , 2013 .

[3]  Michel Perrier,et al.  Extremum-seeking algorithm design for fed-batch cultures of microorganisms with overflow metabolism , 2011 .

[4]  Didier Dumur,et al.  Regulation of lactic acid concentration in its bioproduction from wheat flour , 2016 .

[5]  S. Jana,et al.  RETRACTED ARTICLE: Strategies for efficient production of heterologous proteins in Escherichia coli , 2005, Applied Microbiology and Biotechnology.

[6]  J. Shiloach,et al.  Proposed mechanism of acetate accumulation in two recombinant Escherichia coli strains during high density fermentation. , 1998, Biotechnology and bioengineering.

[7]  Didier Dumur,et al.  Nonlinear Model Predictive Control applied to E. Coli Cultures , 2008 .

[8]  Eugénio C. Ferreira,et al.  Model-based adaptive control of acetate concentration during the production of recombinant proteins , 2002 .

[9]  Peter L. Lee,et al.  Control of anaerobic digesters using Generic Model Control , 1989 .

[10]  Didier Dumur,et al.  Hierarchical Control Strategy based on Robust MPC and Integral Sliding mode - Application to a Continuous Photobioreactor , 2015 .

[11]  Didier Dumur,et al.  A practical robust control scheme for yeast fed-batch cultures – An experimental validation , 2006 .

[12]  Alain Vande Wouwer,et al.  Nonlinear model predictive control of fed-batch cultures of micro-organisms exhibiting overflow metabolism: Assessment and robustness , 2012, Comput. Chem. Eng..

[13]  Peter L. Lee,et al.  Nonlinear Process Control:: Applications Of Generic Model Control , 2011 .

[14]  D. Dochain,et al.  On-Line Estimation and Adaptive Control of Bioreactors , 2013 .

[15]  Laurent Dewasme,et al.  Parameter estimation of a dynamic model of Escherichia coli fed-batch cultures , 2018 .

[16]  G. R. Sullivan,et al.  Generic model control (GMC) , 1988 .

[17]  G. R. Sullivan,et al.  ROBUST STABILITY ANALYSIS OF GENERIC MODEL CONTROL , 1992 .

[18]  W. Deckwer,et al.  High cell density cultivation of Escherichia coli at controlled specific growth rate. , 1991, Journal of biotechnology.

[19]  Alain Vande Wouwer,et al.  Adaptive and Robust Linearizing Control Strategies for Fed-Batch Cultures of Microorganisms Exhibiting Overflow Metabolism , 2010, ICINCO.

[20]  B Sonnleitner,et al.  Growth characteristics of Escherichia coli HB101[pGEc47] on defined medium. , 1998, Biotechnology and bioengineering.

[21]  Anne Richelle,et al.  Linear robust control of S. cerevisiae fed-batch cultures at different scales , 2010 .

[22]  J. Liao,et al.  Escherichia coli as a host for metabolic engineering. , 2018, Metabolic engineering.

[23]  Isabel Rocha.  Model-based strategies for computer-aided operation of recombinant E. coli fermentation , 2003 .

[24]  Rimvydas Simutis,et al.  Generic model control of the specific growth rate in recombinant Escherichia coli cultivations. , 2006, Journal of biotechnology.

[25]  H C Lim,et al.  Acetic acid formation in escherichia coli fermentation , 1992, Biotechnology and bioengineering.

[26]  B Sonnleitner,et al.  Growth of Saccharomyces cerevisiae is controlled by its limited respiratory capacity: Formulation and verification of a hypothesis , 1986, Biotechnology and bioengineering.

[27]  Ute Husemann,et al.  Application of heat compensation calorimetry to an E. coli fed-batch process. , 2018, Journal of biotechnology.

[28]  G. R. Sullivan,et al.  Model based control of a high purity distillation column , 2009 .

[29]  Govind Rao,et al.  Generic model control of induced protein expression in high cell density cultivation of Escherichia coli using on-line GFP-fusion monitoring , 2001 .