Generic model control of induced protein expression in high cell density cultivation of Escherichia coli using on-line GFP-fusion monitoring

A model-based control algorithm (generic model control) is presented for fed-batch cultivation of recombinant Escherichia coli producing either transcriptional or translational fusion products. With the recent development of translational and operon fusions using green fluorescent protein (GFP) [Alb...

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Bibliographic Details
Published in:Bioprocess and biosystems engineering 2001-09, Vol.24 (2), p.83-91
Main Authors: DELISA, M. P, CHAE, H. J, WEIGAND, W. A, VALDES, J. J, RAO, G, BENTLEY, W. E
Format: Article
Language:English
Subjects:
Algorithms
Batch culture
Biological and medical sciences
Biotechnology
Cell density
Compensators
Control algorithms
Control theory
Cultivation
E coli
Escherichia coli
Fluorescence
Fundamental and applied biological sciences. Psychology
Green fluorescent protein
Mathematical models
Methods. Procedures. Technologies
Microbial engineering. Fermentation and microbial culture technology
Model accuracy
Proteins
Response time
Robustness (mathematics)
Time measurement
Translation
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Summary:A model-based control algorithm (generic model control) is presented for fed-batch cultivation of recombinant Escherichia coli producing either transcriptional or translational fusion products. With the recent development of translational and operon fusions using green fluorescent protein (GFP) [Albano et al. (1998) Biotechnol Prog 14:351–354] along with an on-line GFP sensor [Randers-Eichhorn et al. (1997) Biotechnol Bioeng 55:921–926], real-time measurements of foreign protein level are now possible. A mathematical model is presented that is both accurate and simple so as to ensure that all state variables remain observable during cultivation. A balance between model accuracy and mathematical tractability was obtained to facilitate the formulation of the control algorithm. Generic model control (GMC) is a process model-based control algorithm incorporating a process model directly within the control structure. GMC was desirable since linearization of the process model was not necessary and robust performance could be obtained despite process disturbances or plant/model mismatch. Furthermore, a time-delay compensator was built into the control law to account for the observed 90-min lag associated with GFP fluorescence. The feasibility of the GMC algorithm was demonstrated by simulations.
ISSN:1615-7591
1615-7605
DOI:10.1007/s004490100229