Use of a simple mathematical model to predict the behavior of <i>Escherichia coli</i> overproducing β‐lactamase within continuous single‐ and two‐stage reactor systems

Togna, A. Paul; Fu, Jeffrey; Shuler, Michael L.

doi:10.1002/bit.260420503

Cited by 12 publications

(4 citation statements)

References 33 publications

(13 reference statements)

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“…Although a luminous strain of E. coli has been used as a simple model of an autoinductive process, induction and autoinduction of metabolite production are features of many cultures obtained by recombinant DNA technology (e.g., Togna et al, 1993). Moreover, recent studies revealed the distribution of the V. fischeri inducer across a wide range of Gram-positive and Gram-negative genera.…”

Section: Discussionmentioning

confidence: 99%

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Optimal Control of Fed‐Batch Fermentation with Autoinduction of Metabolite Production

Tartakovsky

Ulitzur

Sheintuch

1995

Biotechnology Progress

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Induction of metabolite production is a common feature of many cultures obtained by recombinant DNA technology. Synthesis of a product in these cultures is triggered by a sharp change in environmental conditions or by autoinduction in which the cells, under conditions of growth limitation, produce a species that initiates the synthesis. If product synthesis is the objective of the fermentation, then the time of induction should be optimized so that enough biomass is produced prior to induction while ample nutrient is left in the broth to sustain product synthesis after induction. In this study, recombinant luminous Escherichia coli has been used to portray an autoinductive culture in batch and fed-batch fermentations. A model describing the cell density and substrate and inducer concentrations has been constructed, and its parameters were estimated. An optimal control strategy with three stages of the culture state (growth, inducer synthesis, and growth+product synthesis) was determined and validated experimentally by optimization of the substrate flow rate in a fed-batch fermentation.

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Section: Discussionmentioning

confidence: 99%

“…A number of mathematical models have been developed to describe plasmid instability * Author to whom correspondence should be addressed. (Mosrati et al, 1993) and induction phenomena (Lee and Bailey, 1984;Togna et al, 1993). These are structured models that account for regulation of the expression/ excretion system and for plasmid loss.…”

Section: Introductionmentioning

confidence: 99%

Optimal Control of Fed‐Batch Fermentation with Autoinduction of Metabolite Production

Tartakovsky

Ulitzur

Sheintuch

1995

Biotechnology Progress

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“…It is often the case that the prediction furnished by such a simple model may be better than that of complex structured ones. Modeling of fermentation processes serves to demonstrate the problems mentioned above: while comprehensive structured models of cell metabolism have been already suggested (e.g., Togna et al, 1993) most of the publications on process optimization and control are based on simple unstructured models (e.g., Modak, 1993).…”

Section: Introductionmentioning

confidence: 99%

Variable Structure Models in Process Observation and Control

Tartakovsky¹,

Lewin²,

Sheintuch³

1995

Ind. Eng. Chem. Res.

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A method is proposed for the modeling, observation, and control of processes characterized by sequential transformation steps. Using the method, such processes are described by a battery of alternative submodels, each of which qualitatively represents one of the process steps. The submodels cannot themselves track transitions from step to step. This is handled by switching to an alternative submodel with a significantly better predictive performance than that presently in use. The main advantage of the proposed approach is that each submodel is significantly simpler than the full model of the system. Example applications demonstrate that these submodels, when combined with the switching strategy, are also convenient for parameter estimation, state observation, and regulatory control.

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“…Fed-batch fermentation favors such high cell density cultivations (Yee and Blanch, 1992). However, most analyses of recombinant fermentations have been for continuous operation (Patnaik, 1993;Stephens and Lyberatos, 1988;Togna et al, 1993). This study, therefore, focusses on a fed-batch fermentation for tryptophan synthetase.…”

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confidence: 99%

Plasmid stability analysis in a non‐homogeneous bioreactor for a recombinant fed‐batch fermentation

Patnaik

1999

Can J Chem Eng

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Fed-batch fermentation for tryptophan synthetase by a recombinant Escherichia coli strain has been analyzed through a model incorporating segregational loss of the plasmid pPLc23rrpAl and imperfect macromixing of the broth. These features become significant in large fermentation vessels, where fluid circulation in the bioreactor influences the rates of cell growth and productivity. A simple model consisting of two interacting reactors describes the degree of macromixing, which is characterized by the respective (internal) dilution rates. Controlled imperfect macromixing is superior to other methods in arresting, and even reversing, the normal decline in the concentration of recombinant cells, thereby providing a method to exploit the non-homogeneity of the broth in large bioreactors. Some physical implications are discussed.On a analyst la fermentation en alimentation discontinue pour la synthttase de tryptophan par une souche de Escherichia coli recombinante au moyen d'un modkle incorporant la perte stgrkgationnelle du plasmide pPLc23ttpA I et le macromklange imparfait du bouillon. Ces caracttristiques deviennent significatives dans les rtservoirs de fermentation de grande taille, oh la circulation des fluides dans le biorkacteur influence la vitesse de croissance et la productivitt des cellules. Un modble simple composk de deux rtacteurs qui interagissent dtcrit le degrt de macromtlange, qui est caracttrisk par les vitesses de dilution respectives (internes). Le macromklange imparfait contr6lk est suptrieur ? I celui d'autres mtthodes pour stopper, et m&me inverser, le dkclin normal dans la concentration de cellules recombinantes, ce qui fournit une mtthode pour exploiter la non-homogkntitt du bouillon dans les grands biortacteurs. Certaines implications physiques sont analyskes.

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Use of a simple mathematical model to predict the behavior of Escherichia coli overproducing β‐lactamase within continuous single‐ and two‐stage reactor systems

Cited by 12 publications

References 33 publications

Optimal Control of Fed‐Batch Fermentation with Autoinduction of Metabolite Production

Optimal Control of Fed‐Batch Fermentation with Autoinduction of Metabolite Production

Variable Structure Models in Process Observation and Control

Plasmid stability analysis in a non‐homogeneous bioreactor for a recombinant fed‐batch fermentation

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