A cell population structuring model to estimate recombinant strain growth in a closed system for subsequent search of the mode to increase protein accumulation during protealysin producer cultivation

S P Klykov, V V Kurakov, V B Vilkov, I V Demidyuk, T Yu Gromova and D A Skladnev

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Mathematically modeling the kinetics of batch and continuous cultivation allows you to not only calculate and evaluate the effects of process parameters, but also to forecast those parameters and duration of cultivation to develop a cost-effective production process. Mathematical modeling microorganism cultivation was intensively developed in the second half of the last century.
Dynamics of energy consumption during the growth of photosynthetic Halobacterium salinarum in populations of various age structures has been udied. Changes in the biosynthesis of bacteriorhodopsin, a key retinal containing protein of H.salinarum photosystem, were revealed. For several industrially ignificant strains, exponential accumulation of nonproliferating halobacterium cells, whose growth is limited by different modes of light exposure, was alculated. Various effects of proliferating and nonproliferating cells on bacteriorhodopsin biosynthesis rate were shown. Necessity to prevent influences f other growth limiting factors, except for energy consumption, during halobacterium cultivation was proved using cell population structuring model.
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Chapter 9 Mathematical Modelling in Recombinant Plant Systems: The Challenge to Produce Heterologous Proteins Under GLP/GMP


In the last time and in the near future, the markets are demanding large recombinant proteins production capacity, due to the production levels of traditional platforms will be certainly not suffice to make available these demands (Huang and McDonald, Biotechnol Adv 30:398–409, 2012). The explore of alternative tools to assure adequate supplies for a growing demand constitutes a challenge of present times being the “bioengineered pharmaceutical plant” a promising strategy to respond to this require at affordable costs. However, as a commercial process requires high productivities and product yield at minimum cost, and, also, regulations must be follows like GMP and GLP. A mathematical model like the ones described in the present chapter allows making predictions and control of biosynthesis and yielding into the process.


Keywords: Mathematical modeling,  Recombinant proteins-Nicotiana tabacum-molecular, farming-cell suspension cultures

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