A feedforward-feedback substrate controller based on a Kalman filter for a fed-batch cultivation of Escherichia coli producing phytase

Abstract For the feeding-phase of a batch/fed-batch cultivation of a recombinant Escherichia coli producing extracellular phytase, a controller has been developed. Based on the estimated process variables by a Kalman filter, a feedforward–feedback controller has been implemented in order to maximize the phytase production and to minimize acetate production. The Kalman filter was used to reduce the noise of the glucose measurements and to estimate the biomass concentration, the substrate (glucose) concentration, the maximal growth rate as well as the reaction broth volume, which are used to calculate the feedforward controller contribution. A PI controller was applied to adjust the glucose concentration to the desired set point of 0.2 g/L. The secretion of phytase into the medium is increased at low glucose concentration whereas the acetate production is reduced, due to a low concentration avoiding significant overflow metabolism. The glucose concentration, as the sole measured variable used by the controller, is determined using flow injection analysis (FIA). The operation of the controller as well as its application to the E. coli cultivation is presented. The average on-line measured glucose concentration is 0.208 g/L with a standard deviation of 0.066 g/L. During the cultivation a fault occurred in the measurement system. The response of the controller system with respect to this fault is discussed in detail. Compared to a controller based on oxygen measurements, the yield of phytase is the same with the presented system.

[1]  E. Flaschel,et al.  Overexpression of the phytase from Escherichia coli and its extracellular production in bioreactors , 2002, Applied Microbiology and Biotechnology.

[2]  G W Luli,et al.  A predictive and feedback control algorithm maintains a constant glucose concentration in fed-batch fermentations , 1991, Applied and environmental microbiology.

[3]  P. Hagander,et al.  Avoiding acetate accumulation in Escherichia coli cultures using feedback control of glucose feeding. , 2001, Biotechnology and bioengineering.

[4]  Robert Babuska,et al.  Fuzzy self-tuning PI control of pH in fermentation , 2002 .

[5]  W. Johnston,et al.  Industrial control of recombinant E. coli fed-batch culture: new perspectives on traditional controlled variables , 2002, Bioprocess and biosystems engineering.

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

[7]  P Neubauer,et al.  Determination of the maximum specific uptake capacities for glucose and oxygen in glucose-limited fed-batch cultivations of Escherichia coli. , 2001, Biotechnology and bioengineering.

[8]  Bernd Hitzmann,et al.  The control of glucose concentration during yeast fed-batch cultivation using a fast measurement complemented by an extended Kalman filter , 2000 .

[9]  Jens Brandt,et al.  Knowledge-based fault detection and diagnosis in flow-injection analysis , 1994 .

[10]  Hisbullah,et al.  Comparative evaluation of various control schemes for fed-batch fermentation , 2002 .

[11]  Iqbal M. Mujtaba,et al.  Performance of different types of controllers in tracking optimal temperature profiles in batch reactors , 2000 .

[12]  Bernd Hitzmann,et al.  A knowledge-based system for real-time validation of calibrations and measurements , 1999 .

[13]  A. Plückthun,et al.  High volumetric yields of functional dimeric miniantibodies in Escherichia coli, using an optimized expression vector and high-cell-density fermentation under non-limited growth conditions , 1996, Applied Microbiology and Biotechnology.

[14]  E. Flaschel,et al.  Optimization of the extracellular production of a bacterial phytase with Escherichia coli by using different fed-batch fermentation strategies , 2003, Applied Microbiology and Biotechnology.

[15]  Bernd Hitzmann,et al.  Kalman Filter Based Glucose Control at Small Set Points during Fed‐Batch Cultivation of Saccharomyces cerevisiae , 2008, Biotechnology progress.

[16]  K. Yamuna Rani,et al.  Control of fermenters : a review , 1999 .