Regulation of <i>lac</i> operon expression in mixed sugar chemostat cultures

Ray, N. G.; Vieth, W. R.; Venκatasubramanian, Κ.

doi:10.1002/bit.260290812

Cited by 11 publications

(1 citation statement)

References 39 publications

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“…Furthermore, Ray et al (30) presented the first unified lac operon model that incorporated the role of the catabolite modulator factor in the regulation of transcription. Chung and Stephanopoulos (31) presented a minimal yet elegant lac operon model that takes into account repression and induction, as well as the positive feedback generated by the LacY permease.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Deterministic and Stochastic Models of the lac Operon Genetic Network

Stamatakis

Mantzaris

2009

Biophysical Journal

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The lac operon has been a paradigm for genetic regulation with positive feedback, and several modeling studies have described its dynamics at various levels of detail. However, it has not yet been analyzed how stochasticity can enrich the system's behavior, creating effects that are not observed in the deterministic case. To address this problem we use a comparative approach. We develop a reaction network for the dynamics of the lac operon genetic switch and derive corresponding deterministic and stochastic models that incorporate biological details. We then analyze the effects of key biomolecular mechanisms, such as promoter strength and binding affinities, on the behavior of the models. No assumptions or approximations are made when building the models other than those utilized in the reaction network. Thus, we are able to carry out a meaningful comparison between the predictions of the two models to demonstrate genuine effects of stochasticity. Such a comparison reveals that in the presence of stochasticity, certain biomolecular mechanisms can profoundly influence the region where the system exhibits bistability, a key characteristic of the lac operon dynamics. For these cases, the temporal asymptotic behavior of the deterministic model remains unchanged, indicating a role of stochasticity in modulating the behavior of the system.

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Section: Introductionmentioning

confidence: 99%

Comparison of Deterministic and Stochastic Models of the lac Operon Genetic Network

Stamatakis

Mantzaris

2009

Biophysical Journal

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Dual substrate removal by an axenic bacterial culture

Machado

Grady

1989

Biotech & Bioengineering

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A pure bacterial culture capable of utilizing either L-lysine or 2-chlorophenol (2-CP) as sole carbon source was isolated and used in continuous culture experiments to determine its response to dual substrate limitation by those two compounds. Dilution rate and feed composition were each set at three levels in a two factorial experimental design. The total chemical oxygen demand (COD) of the feed was fixed at 225 mg/L and its composition was varied by changing the ratio of lysine to 2-CP. The effects of the two independent variables (dilution rate and feed composition) on the concentrations of cells, lysine, COD, and dissolved organic carbon (DOC) in the reactors were systematic whereas the effects on the 2-CP concentration were less predictable. The concentrations of the two substrates responded to the two independent variables in a complex interactive manner which is not explained by existing models for dual, substitutable substrates. Rather, the results suggested that the prediction of the fate of a single organic component in a reactor receiving a multicomponent feed is a very difficult task.

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Overexpression of cloned genes using recombinant escherichia coli regulated by a T7 promoter: II. Two‐stage continuous cultures and model simulations

Miao

Kompala

1993

Biotech & Bioengineering

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A two-stage culture strategy was studied for continuous high-level production of a foreign protein in the chemically inducible T7 expression system. The first stage is dedicated to the maintenance of plasmid-bearing cells and the second stage to the target protein synthesis by induction of cells coming from the first stage. On entering the second stage, recombinant cells undergo a gradual induction of the target gene expression. These plasmid-bearing cells experience dynamic changes in intracellular compositions and specific growth rates with their individual residence times. Therefore, the overall cultural characteristics in the production stage are really averages of the contributions from the various cells with different residence times. The behavior of the two-stage culture is described by a model, which accounts for dynamic variations of cell growth and protein synthesis rates with cell residence times. Model simulations were compared with experimental results at a variety of operating conditions such as inducer concentration and dilution rate. This model is useful for understanding the behavior of two-stage continuous cultures.

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Regulation of lac operon expression in mixed sugar chemostat cultures

Cited by 11 publications

References 39 publications

Comparison of Deterministic and Stochastic Models of the lac Operon Genetic Network

Comparison of Deterministic and Stochastic Models of the lac Operon Genetic Network

Dual substrate removal by an axenic bacterial culture

Overexpression of cloned genes using recombinant escherichia coli regulated by a T7 promoter: II. Two‐stage continuous cultures and model simulations

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