Journal ArticleDOI
Substrate gradient formation in the large-scale bioreactor lowers cell yield and increases by-product formation
TLDR
IPTG induction of a recombinant protein was shown to influence important cell parameters and considerably increased the yield of carbon dioxide per glucose added, indicating an increased maintenance in the large-scale bioreactor.Abstract:
A heterogeneous micro-environment was identified in a 12 m3 bioreactor with a height-to-diameter ratio of 2.5. The reactor was aerated by a ring sparger and stirred by three Rushton turbines. E. coli cells were cultivated in minimal medium to a cell density in the order of 30 g/l. Samples of glucose, the growth limiting component fed to the process, were taken at three levels in the bioreactor (top/middle/bottom). These showed that glucose concentration declined away from the feedpoint. The gradients depended on the mixing characteristics of the feedpoint, and concentrations of up to 400 times the mean value were found when feed was added to a relatively stagnant mixing zone. This resulted in up to 20% lower biomass yield compared to the bench scale. Gradients also affected the by-product formation, resulting in acetate formation in the large-scale bioreactor. IPTG induction of a recombinant protein was shown to influence important cell parameters and considerably increased the yield of carbon dioxide per glucose added, indicating an increased maintenance. The product formation rate was, however, not notably affected by the scale-up.read more
Citations
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Journal ArticleDOI
Physiological responses to mixing in large scale bioreactors
Sven-Olof Enfors,Mehmedalija Jahic,A. Rozkov,Bo Xu,Michael Hecker,Britta Jürgen,Elke Krüger,Thomas Schweder,G. Hamer,D. O'Beirne,Naruemol Noisommit-Rizzi,Matthias Reuss,L. Boone,Christopher J. Hewitt,Caroline M. McFarlane,Alvin W. Nienow,Tamas Kovacs,Christian Trägårdh,Laszlo Fuchs,Johan Revstedt,P. C. Friberg,Bjørn H. Hjertager,G. Blomsten,Harald Skogman,S. Hjort,Frans W. J. M. M. Hoeks,H. Y. Lin,Peter Neubauer,R. G. J. M. van der Lans,Karel Ch. A. M. Luyben,Peter Vrábel,A. Manelius +31 more
TL;DR: Flow cytometric analysis revealed reduced damage with respect to cytoplasmic membrane potential and integrity in cells grown in the dynamic environments of the large scale reactor and the scale-down reactor.
Journal ArticleDOI
Living with heterogeneities in bioreactors: understanding the effects of environmental gradients on cells.
TL;DR: In this review, the theoretical analyses that predict the existence of environmental gradients in bioreactors and their experimental confirmation are reviewed and studies based on the scale-down methodology, a convenient tool for assessing the effect of environmental heterogene ities, are surveyed.
Journal ArticleDOI
Optimization and scale up of industrial fermentation processes
TL;DR: An overview on the problems typically coming along with fermentation process optimization and scale up is given, and currently applied scale-up strategies while considering future technologies are presented, with emphasis on Escherichia coli as one of the most commonly fermented organisms.
Journal ArticleDOI
Synthetic and systems biology for microbial production of commodity chemicals.
Victor Chubukov,Victor Chubukov,Aindrila Mukhopadhyay,Aindrila Mukhopadhyay,Christopher J. Petzold,Christopher J. Petzold,Jay D. Keasling,Hector Garcia Martin,Hector Garcia Martin +8 more
TL;DR: The path from the choice of target molecule to scaling production up to commercial volumes is described, and some of the current challenges and gaps in knowledge that must be overcome are presented in order to bring bioengineering capabilities to the level of other engineering disciplines.
Journal ArticleDOI
Mixing in large-scale vessels stirred with multiple radial or radial and axial up-pumping impellers: modelling and measurements
TL;DR: In this article, the authors used the Compartment Model Approach (CMA) to develop a flow model based on the general knowledge of the hydrodynamics of both unaerated and aerated stirred vessels.
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Physiological responses to mixing in large scale bioreactors
Sven-Olof Enfors,Mehmedalija Jahic,A. Rozkov,Bo Xu,Michael Hecker,Britta Jürgen,Elke Krüger,Thomas Schweder,G. Hamer,D. O'Beirne,Naruemol Noisommit-Rizzi,Matthias Reuss,L. Boone,Christopher J. Hewitt,Caroline M. McFarlane,Alvin W. Nienow,Tamas Kovacs,Christian Trägårdh,Laszlo Fuchs,Johan Revstedt,P. C. Friberg,Bjørn H. Hjertager,G. Blomsten,Harald Skogman,S. Hjort,Frans W. J. M. M. Hoeks,H. Y. Lin,Peter Neubauer,R. G. J. M. van der Lans,Karel Ch. A. M. Luyben,Peter Vrábel,A. Manelius +31 more