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Application of dynamic flux balance analysis to an industrial Escherichia coli fermentation

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Title: Application of dynamic flux balance analysis to an industrial Escherichia coli fermentation
Authors: Meadows, Adam L. adameadows@gmail.com, Karnik, Rahi1, Lam, Harry1, Forestell, Sean1, Snedecor, Brad1
Source: Metabolic Engineering. Mar2010, Vol. 12 Issue 2, p150-160. 11p.
Subjects: Escherichia coli, Fermentation, Bacterial metabolism, Bacterial growth, Bioreactors, Recombinant proteins
Abstract: Abstract: We have developed a reactor-scale model of Escherichia coli metabolism and growth in a 1000L process for the production of a recombinant therapeutic protein. The model consists of two distinct parts: (1) a dynamic, process specific portion that describes the time evolution of 37 process variables of relevance and (2) a flux balance based, 123-reaction metabolic model of E. coli metabolism. This model combines several previously reported modeling approaches including a growth rate-dependent biomass composition, maximum growth rate objective function, and dynamic flux balancing. In addition, we introduce concentration-dependent boundary conditions of transport fluxes, dynamic maintenance demands, and a state-dependent cellular objective. This formulation was able to describe specific runs with high-fidelity over process conditions including rich media, simultaneous acetate and glucose consumption, glucose minimal media, and phosphate depleted media. Furthermore, the model accurately describes the effect of process perturbations—such as glucose overbatching and insufficient aeration—on growth, metabolism, and titer. [Copyright &y& Elsevier]
Copyright of Metabolic Engineering is the property of Academic Press Inc. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
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DbLabel: Engineering Source
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PubType: Academic Journal
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  Data: Application of dynamic flux balance analysis to an industrial Escherichia coli fermentation
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  Data: <searchLink fieldCode="AR" term="%22Meadows%2C+Adam+L%2E%22">Meadows, Adam L.</searchLink><i> adameadows@gmail.com</i><br /><searchLink fieldCode="AR" term="%22Karnik%2C+Rahi%22">Karnik, Rahi</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Lam%2C+Harry%22">Lam, Harry</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Forestell%2C+Sean%22">Forestell, Sean</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Snedecor%2C+Brad%22">Snedecor, Brad</searchLink><relatesTo>1</relatesTo>
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  Data: <searchLink fieldCode="JN" term="%22Metabolic+Engineering%22">Metabolic Engineering</searchLink>. Mar2010, Vol. 12 Issue 2, p150-160. 11p.
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  Data: <searchLink fieldCode="DE" term="%22Escherichia+coli%22">Escherichia coli</searchLink><br /><searchLink fieldCode="DE" term="%22Fermentation%22">Fermentation</searchLink><br /><searchLink fieldCode="DE" term="%22Bacterial+metabolism%22">Bacterial metabolism</searchLink><br /><searchLink fieldCode="DE" term="%22Bacterial+growth%22">Bacterial growth</searchLink><br /><searchLink fieldCode="DE" term="%22Bioreactors%22">Bioreactors</searchLink><br /><searchLink fieldCode="DE" term="%22Recombinant+proteins%22">Recombinant proteins</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Abstract: We have developed a reactor-scale model of Escherichia coli metabolism and growth in a 1000L process for the production of a recombinant therapeutic protein. The model consists of two distinct parts: (1) a dynamic, process specific portion that describes the time evolution of 37 process variables of relevance and (2) a flux balance based, 123-reaction metabolic model of E. coli metabolism. This model combines several previously reported modeling approaches including a growth rate-dependent biomass composition, maximum growth rate objective function, and dynamic flux balancing. In addition, we introduce concentration-dependent boundary conditions of transport fluxes, dynamic maintenance demands, and a state-dependent cellular objective. This formulation was able to describe specific runs with high-fidelity over process conditions including rich media, simultaneous acetate and glucose consumption, glucose minimal media, and phosphate depleted media. Furthermore, the model accurately describes the effect of process perturbations—such as glucose overbatching and insufficient aeration—on growth, metabolism, and titer. [Copyright &y& Elsevier]
– Name: AbstractSuppliedCopyright
  Label:
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  Data: <i>Copyright of Metabolic Engineering is the property of Academic Press Inc. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1016/j.ymben.2009.07.006
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      – Code: eng
        Text: English
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        PageCount: 11
        StartPage: 150
    Subjects:
      – SubjectFull: Escherichia coli
        Type: general
      – SubjectFull: Fermentation
        Type: general
      – SubjectFull: Bacterial metabolism
        Type: general
      – SubjectFull: Bacterial growth
        Type: general
      – SubjectFull: Bioreactors
        Type: general
      – SubjectFull: Recombinant proteins
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      – TitleFull: Application of dynamic flux balance analysis to an industrial Escherichia coli fermentation
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            NameFull: Karnik, Rahi
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            NameFull: Lam, Harry
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            NameFull: Forestell, Sean
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              Text: Mar2010
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              Y: 2010
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