Mathematical model for the application of Metabolic Flux Analysis to CHO cells producing recombinant human erythropoietin

Mathematical modeling of metabolism meets several important applications in the context of bioprocess engineering, such as the interpretation of cell physiology. Metabolic Flux Analysis, one of the tools of this discipline, was used in the present work to characterize the biosynthesis of recombinant...

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Main Authors: Osmán Fernández, Julio C Dustet, Ernesto Chico
Format: Article
Language:English
Published: Elfos Scientiae
Series:Biotecnología Aplicada
Subjects:
Online Access:http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S1027-28522012000400004&lng=en&tlng=en
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author Osmán Fernández
Julio C Dustet
Ernesto Chico
author_facet Osmán Fernández
Julio C Dustet
Ernesto Chico
author_sort Osmán Fernández
collection DOAJ
description Mathematical modeling of metabolism meets several important applications in the context of bioprocess engineering, such as the interpretation of cell physiology. Metabolic Flux Analysis, one of the tools of this discipline, was used in the present work to characterize the biosynthesis of recombinant human erythropoietin in CHO cells. In order to apply this method, we built a matrix of stoichiometric numbers representing the major metabolic pathways for the generation of energy and the synthesis of essential precursors for product and biomass accumulation. Equations representing the biosynthesis of recombinant human erythropoietin and the growth of CHO were also derived, conferring an advantage to the proposed model over other existing designs. The dimensions of the obtained matrix were 47 × 44, with a rank of 44 and a condition number of 83; therefore, the model has a unique solution and is not sensitive. The metabolic flux map obtained by solving the mathematical model using experimental data showed results consistent with the known biochemistry of CHO cells and with the findings of other reports on this and other mammalian cell lines. The general steps of the methodology used to obtain the proposed mathematical model are also outlined.
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spelling doaj.art-3f1f1c0286164af5b8a22bbd7538f2a32022-12-21T19:16:06ZengElfos ScientiaeBiotecnología Aplicada1027-2852294246252S1027-28522012000400004Mathematical model for the application of Metabolic Flux Analysis to CHO cells producing recombinant human erythropoietinOsmán Fernández0Julio C Dustet1Ernesto Chico2Centro de Inmunología MolecularInstituto Superior Politécnico José Antonio EcheverríaCentro de Inmunología MolecularMathematical modeling of metabolism meets several important applications in the context of bioprocess engineering, such as the interpretation of cell physiology. Metabolic Flux Analysis, one of the tools of this discipline, was used in the present work to characterize the biosynthesis of recombinant human erythropoietin in CHO cells. In order to apply this method, we built a matrix of stoichiometric numbers representing the major metabolic pathways for the generation of energy and the synthesis of essential precursors for product and biomass accumulation. Equations representing the biosynthesis of recombinant human erythropoietin and the growth of CHO were also derived, conferring an advantage to the proposed model over other existing designs. The dimensions of the obtained matrix were 47 × 44, with a rank of 44 and a condition number of 83; therefore, the model has a unique solution and is not sensitive. The metabolic flux map obtained by solving the mathematical model using experimental data showed results consistent with the known biochemistry of CHO cells and with the findings of other reports on this and other mammalian cell lines. The general steps of the methodology used to obtain the proposed mathematical model are also outlined.http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S1027-28522012000400004&lng=en&tlng=enmetabolic flux analysismetabolismmathematical modelchoepo
spellingShingle Osmán Fernández
Julio C Dustet
Ernesto Chico
Mathematical model for the application of Metabolic Flux Analysis to CHO cells producing recombinant human erythropoietin
Biotecnología Aplicada
metabolic flux analysis
metabolism
mathematical model
cho
epo
title Mathematical model for the application of Metabolic Flux Analysis to CHO cells producing recombinant human erythropoietin
title_full Mathematical model for the application of Metabolic Flux Analysis to CHO cells producing recombinant human erythropoietin
title_fullStr Mathematical model for the application of Metabolic Flux Analysis to CHO cells producing recombinant human erythropoietin
title_full_unstemmed Mathematical model for the application of Metabolic Flux Analysis to CHO cells producing recombinant human erythropoietin
title_short Mathematical model for the application of Metabolic Flux Analysis to CHO cells producing recombinant human erythropoietin
title_sort mathematical model for the application of metabolic flux analysis to cho cells producing recombinant human erythropoietin
topic metabolic flux analysis
metabolism
mathematical model
cho
epo
url http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S1027-28522012000400004&lng=en&tlng=en
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AT ernestochico mathematicalmodelfortheapplicationofmetabolicfluxanalysistochocellsproducingrecombinanthumanerythropoietin