Abstract
A modelling approach of the plasmid instability of a recombinant strain, here the bacteria Escherichia coli, is proposed. It is based on the fact that a recombinant cell suspension can be regarded as a mixed culture where several kinds of strain having 0, 1, 2...... or N plasmids can coexist. This approach tries to clarify the mass balance of each fraction, by differentiating the kinetics of growth from the kinetics of evolution of the plasmid copy number. Parametric identification was carried out on a continuous culture, using an algorithm of the Simplex type. The model thus obtained was confronted with experimental results obtained during continuous and batch cultures. If the correspondence is not perfect, the shape of the simulated curves corroborates more correctly than before the experimental results. So this model is a further step towards a complete model that is able to simulate the evolutions of the total biomass, of the substrate, and of each cell populations characterised by a given plasmid copy number. Further work will deepen this modelling approach, particularly by introducing a variation of the growth rate as a function of the plasmid copy number.
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© 2001 Springer Science+Business Media Dordrecht
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Boudrant, J., Le, B., Fournier, F., Fonteix, C. (2001). Modelling of Segregational Plasmid Instability of Recombinant Strain Suspension of Escherichia coli . In: Merten, OW., et al. Recombinant Protein Production with Prokaryotic and Eukaryotic Cells. A Comparative View on Host Physiology. Springer, Dordrecht. https://doi.org/10.1007/978-94-015-9749-4_10
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DOI: https://doi.org/10.1007/978-94-015-9749-4_10
Publisher Name: Springer, Dordrecht
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