scholarly journals Tryptophan Production Maximization in a Fed-Batch Bioreactor with Modified E. coli Cells, by Optimizing Its Operating Policy Based on an Extended Structured Cell Kinetic Model

2021 ◽  
Vol 8 (12) ◽  
pp. 210
Author(s):  
Gheorghe Maria ◽  
Laura Renea
Keyword(s):  
Cell Model ◽  
Genetically Modify ◽  
Optimal Operation ◽  
Coli Strain ◽  
Operating Conditions ◽  
Model Complexity ◽  
State Variables ◽  
Fed Batch ◽  
E Coli ◽  
Batch Bioreactor

Hybrid kinetic models, linking structured cell metabolic processes to the dynamics of macroscopic variables of the bioreactor, are more and more used in engineering evaluations to derive more precise predictions of the process dynamics under variable operating conditions. Depending on the cell model complexity, such a math tool can be used to evaluate the metabolic fluxes in relation to the bioreactor operating conditions, thus suggesting ways to genetically modify the microorganism for certain purposes. Even if development of such an extended dynamic model requires more experimental and computational efforts, its use is advantageous. The approached probative example refers to a model simulating the dynamics of nanoscale variables from several pathways of the central carbon metabolism (CCM) of E. coli cells, linked to the macroscopic state variables of a fed-batch bioreactor (FBR) used for the tryptophan (TRP) production. The used E. coli strain was modified to replace the PTS system for glucose (GLC) uptake with a more efficient one. The study presents multiple elements of novelty: (i) the experimentally validated modular model itself, and (ii) its efficiency in computationally deriving an optimal operation policy of the FBR.

Identification and Optimization of Recombinant E. coli Fed-Batch Fermentation Producing γ-Interferon Protein

2013 ◽  
Vol 11 (1) ◽  
pp. 123-134
Author(s):  
Mahdi Feyzdar ◽  
Ahmad Reza Vali ◽  
Valiollah Babaeipour
Keyword(s):  
Neural Network ◽  
Batch Cultivation ◽  
Model Complexity ◽  
Fed Batch ◽  
E Coli ◽  
Novel Approach ◽  
Fed Batch Fermentation ◽  
Optimal Brain Surgeon ◽  
Fed Batch Cultivation ◽  
Γ Interferon

Abstract A novel approach to identification of fed-batch cultivation of E. coli BL21 (DE3) has been presented. The process has been identified in the system that is designed for maximum production of γ-interferon protein. Dynamic order of the process has been determined by Lipschitz test. Multilayer Perceptron neural network has been used to process identification by experimental data. The optimal brain surgeon method is used to reduce the model complexity that can be easily implemented. Validation results base on autocorrelation function of the residuals, show good performance of neural network and make it possible to use of it in process analyses.

scholarly journals Model-Based Optimization of a Fed-Batch Bioreactor for mAb Production Using a Hybridoma Cell Culture

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5648
Author(s):  
Gheorghe Maria
Keyword(s):  
Control Variable ◽  
Engineering Problem ◽  
Raw Material ◽  
State Variables ◽  
Fed Batch ◽  
Control Variables ◽  
Model Based ◽  
Batch Bioreactor ◽  
Decision Control ◽  
Highly Nonlinear

Production of monoclonal antibodies (mAbs) is a well-known method used to synthesize a large number of identical antibodies, which are molecules of huge importance in medicine. Due to such reasons, intense efforts have been invested to maximize the mAbs production in bioreactors with hybridoma cell cultures. However, the optimal control of such sensitive bioreactors is an engineering problem difficult to solve due to the large number of state-variables with highly nonlinear dynamics, which often translates into a non-convex optimization problem that involves a significant number of decision (control) variables. Based on an adequate kinetic model adopted from the literature, this paper focuses on developing an in-silico (model-based, offline) numerical analysis of a fed-batch bioreactor (FBR) with an immobilized hybridoma culture to determine its optimal feeding policy by considering a small number of control variables, thus ensuring maximization of mAbs production. The obtained time stepwise optimal feeding policies of FBR were proven to obtain better performances than those of simple batch operation (BR) for all the verified alternatives in terms of raw material consumption and mAbs productivity. Several elements of novelty (i–iv) are pointed out in the “conclusions” section (e.g., considering the continuously added biomass as a control variable during FBR).

scholarly journals Iterative Design of Dynamic Experiments in Modeling for Optimization of Innovative Bioprocesses

2009 ◽  
Vol 4 (2) ◽  
Author(s):  
Mariano Cristaldi ◽  
Ricardo Grau ◽  
Ernesto Martinez
Keyword(s):  
Data Gathering ◽  
Parametric Uncertainty ◽  
Coli Strain ◽  
Operating Conditions ◽  
Batch Bioreactor ◽  
Dynamic Experiments ◽  
Speed Up ◽  
Interleukin 11 ◽  
Experimental Runs ◽  
Sampling Times

Finding optimal operating conditions fast with a scarce budget of experimental runs is a key problem to speed up the development and scaling up of innovative bioprocesses. In this paper, a novel iterative methodology for the model-based design of dynamic experiments in modeling for optimization is developed and successfully applied to the optimization of a fed-batch bioreactor related to the production of r-interleukin-11 (rIL-11) whose DNA sequence has been cloned in an Escherichia coli strain. At each iteration, the proposed methodology resorts to a library of tendency models to increasingly bias bioreactor operating conditions towards an optimum. By selecting the ‘most informative’ tendency model in the sequel, the next dynamic experiment is defined by re-optimizing the input policy and calculating optimal sampling times. Model selection is based on minimizing an error measure which distinguishes between parametric and structural uncertainty to selectively bias data gathering towards improved operating conditions. The parametric uncertainty of tendency models is iteratively reduced using Global Sensitivity Analysis (GSA) to pinpoint which parameters are keys for estimating the objective function. Results obtained after just a few iterations are very promising.

Expression of Bacillus amyloliquefaciens transglutaminase in recombinant E. coli under the control of a bicistronic plasmid system in DO-stat fed-batch bioreactor cultivations

2021 ◽  
Author(s):  
Lovaine Silva Duarte ◽  
Carla Roberta Matte ◽  
Paulo Roberto Dall Cortivo ◽  
José Eduardo Sacconi Nunes ◽  
Laisa Quadros Barsé ◽  
...  
Keyword(s):  
Bacillus Amyloliquefaciens ◽  
Fed Batch ◽  
E Coli ◽  
Batch Bioreactor

Simulation of UDMC on a Fed-Batch Bioreactor

1988 ◽  
Author(s):  
Hsin-Ying Lin ◽  
John C. Lewis ◽  
Richard H. Luecke
Keyword(s):  
Fed Batch ◽  
Batch Bioreactor

Transport of escherichia coli through soil to groundwater traced by randomly amplified polymorphic DNA (RAPD)

1997 ◽  
Vol 35 (11-12) ◽  
pp. 351-357 ◽  
Author(s):  
R. Rothmaier ◽  
A. Weidenmann ◽  
K. Botzenhart
Keyword(s):  
Negative Impact ◽  
Random Amplified Polymorphic Dna ◽  
Coli Strain ◽  
Soil Samples ◽  
Test Field ◽  
Liquid Manure ◽  
E Coli ◽  
Rapd Pattern ◽  
Geological Situation ◽  
Different Strains

Isolates (50) of E. coli obtained from liquid manure (20 bovine, 20 porcine) were genotyped using random amplified polymorphic DNA (RAPD). Typing revealed 9 and 14 different strains in bovine and porcine liquid manure respectively with no strains in common. One porcine strain, showing a simple RAPD pattern, was subcultured and spread on a test field (1.5l/m2 at 1010 cfu/l) in a drinking water protection zone with loamy to sandy sediments in the Donauried area, Baden-Wurttemberg. Soil samples and groundwaters were collected at monthly intervals October 1994 – June 1995 during which 114 E. coli isolates were recovered. The first occurrence and maximum concentration of E. coli in soil samples taken from more than 20cm depth was in January 1995, declining rapidly with depth and time. All isolates from soil and only one from groundwater showed the RAPD pattern of the spread E. coli strain. The results could not demonstrate a severe negative impact of the spreading of liquid manure on the bacteriological quality of the groundwater in the given geological situation. The distinct strain patterns found in different kinds of liquid manure suggest that genotyping of E. coli by RAPD may be an adequate tool for tracing sources of faecal contamination.

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