Theoretical Analysis of the Effect of Cell Recycling on Recombinant Cell Fermentation Processes

Park, Tai Hyun; Hong, Juan; Lim, Henry C.

doi:10.1021/bp00008a001

Cited by 11 publications

(2 citation statements)

References 8 publications

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“…Although the recycle of cells back to the fermentor after downstream microfiltration recovery was for simplicity not simulated, it is essential to note the potential outcomes if it were. The fermentation industry has long recognized the benefits of cell recycle using membranes or even expanded-bed adsorbers for increasing cell density and volumetric productivity in fermentations, and its mathematical depiction can include such things as a recycle ratio in the mass balances [66,67]. In one study, a cell-recycled A. succiniciproducens fermentation achieved a high cell concentration of 6.5 g DCW /L and a three-times higher succinic acid productivity compared to batch culture, without (1) morphologically changing to an inactive spherical state at the stressful high shear rates of 800 rpm that were used to limit membrane fouling, and (2) without becoming CO 2 -limited even at the highly-consuming recycled high cell densities by virtue of the concurrent supply of both pH neutralizer and inorganic carbon in the form of NaHCO 3 and Na 2 CO 3 [68].…”

Section: Resultsmentioning

confidence: 99%

Simulation with Computational Fluid Dynamics of Succinic Acid and Co-Product Biorefinery Process

Wensel¹

2011

J Bioprocess Biotech

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Succinic acid is a di-carboxylic acid with tremendous future market potential, and there is increasing interest to produce it from microorganisms using cheap renewable resources like biomass. However, commercialization of bio-succinic acid is currently challenged by limited profitability of processes devoted solely to succinic acid, high downstream process costs, and minimal available industrial-scale simulation. To address these limitations, a novel industrial-scale biorefinery process to convert corn-stover into succinic acid and co-products was simulated using an integrated mathematical model developed from reported laboratory-scale experimental data. The upstream section of the biorefinery featured handling, pre-treatment, conversion, and separation of corn stover feedstock into a liquid fraction for ethanol processing and a solids fraction containing mostly cellulose that was further hydrolyzed into glucose for succinic acid processing. Subsequent units of operation were then simulated for a baseline process: Microfiltration was used to remove residual insoluble lignin, and glucose was then continuously fermented by the strain M. Succiniciproducens MBEL55E to produce succinate and by-products acetate, lactate, and formate. Additional steps to recover and purify succinic acid included cell microfiltration for cell removal, moving-bed adsorption for sugar removal and decolorization, nanofiltration for separation of succinate primarily from other salts, ion exchange for acidification and purification, and finally crystallization. The finite volume method of Computational Fluid Dynamics (CFD) was coupled with kinetic, stochiometric, mass, and energy balance equations to simulate the effects of inlet temperature impeller speed, diameter, and spacing, as well as inlet temperature and fermentor volume, on fermentor cooling jacket heat transfer area. Predicted dissolved CO 2 concentrations in the fermentor were in agreement with those in literature. The effects of microfiltration recirculation rate, microfiltration stage numbers, and adsorber sorbent particle diameter on dimensional requirements and power consumption were additionally evaluated. Yields and estimated volume and area requirements for units of operation were obtained for the baseline process and for those involving the simulated variable changes. This work represents the first reported industrial-scale bio-succinic acid process model.

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Section: Resultsmentioning

confidence: 99%

Simulation with Computational Fluid Dynamics of Succinic Acid and Co-Product Biorefinery Process

Wensel¹

2011

J Bioprocess Biotech

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“…The residence time distribution of the cell in the second tank should be taken into account for the material balances. Park et al [7] derived the probability density for the residence time distribution using population balance and three different cases were considered according to the study objective. Model equations for cell lysis and product formation induction of E. coli containing bacteriophage k were set up and productivity in two-stage continuous operation was calculated by taking the residence time distribution into account in this article.…”

Section: Introductionmentioning

confidence: 99%

Analysis of two-stage continuous operation of Escherichia coli containing bacteriophage λ vector

Park

2000

Bioprocess Engineering

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Bacteriophage k containing a cloned-gene is stably maintained in Escherichia coli in the lysogenic state while it is replicated and it overproduces a recombinant protein product in the lytic state. The host cell is eventually lysed in the lytic state. The kinetics of cell lysis and production induction were studied and are reported in this article through model equations. In two-stage continuous operation, the ®rst tank is maintained in the lysogenic state for cell growth and cloned-gene stability while the second tank is in the lytic state for the overproduction of cloned-gene product. Individual cells in the second tank have different extent of the induction for product formation, since each has a different residence time. The different residence time for individual cells was taken into account using a population model. The numerical results show good agreement with the experimental data for the prediction of dilution rate in the second tank which gives the maximum product concentration.List of symbols D dilution rate, h À1

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Effects of oxygen and ethanol on recombinant yeast fermentation for hepatitis B virus surface antigen production: Modeling and simulation studies

Shi

Ryu

Yuan

1993

Biotech & Bioengineering

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A model was formulated to examine the competitive growth of two phenotypes (Leu(+) and Leu(-)) and the product formation with recombinant Saccharomyces cerevisiae strain DBY-745, which contains the shuttle vector pYGH3-16-s with the foreign gene HBsAg (hepatitis B virus surface antigen) as well as experimental fedbatch fermentation data. The important state variables and the process parameters evaluated include (1) the ratio of the plasmid-free cell concentration to the plasmid-containing cell concentration (rho = X(-)X(+)), (2) the expression of human hepatitis B surface antigen g (CH), (3) the glucose consumption (S), (4) the ethanol production (/), (5) the change of working volume (V) in the fermentor, (6) the different specific growth rates of two phenotype cells, and (7) the plasmid loss frequency coefficient (alpha ). These variables and other parameters were carefully defined, their correlations were studied, and a mathematical model using a set of nonlinear ordinary differential equations (ODEs) for fed-batch fermentation was then obtained based on the theoretical considerations and the experimental results. The extended Kalman filter (EKF) methods was applied for the best estimate of these variables based on the experimentally observable variables: rhoV, and g (CH). Each of these variable was affected by random measuring errors under the different operating conditions. Simulation results presented for verification of the model agreed with our observations and provided useful information relevant to the operation and the control of the fedbatch recombinant yeast fermentation. The method of predicting an optimal profile of the cell growth was also demonstrated under the different dissolved oxygen concentrations.

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Theoretical Analysis of the Effect of Cell Recycling on Recombinant Cell Fermentation Processes

Cited by 11 publications

References 8 publications

Simulation with Computational Fluid Dynamics of Succinic Acid and Co-Product Biorefinery Process

Simulation with Computational Fluid Dynamics of Succinic Acid and Co-Product Biorefinery Process

Analysis of two-stage continuous operation of Escherichia coli containing bacteriophage λ vector

Effects of oxygen and ethanol on recombinant yeast fermentation for hepatitis B virus surface antigen production: Modeling and simulation studies

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