Abstract
A chemostat cell culture is a polyphasic dispersed system. Three models using net transport and metabolization (T/M) kinetics of hyperbolic form have been described. The first uses only one metabolic pathway and has been studied under various conditions. The second uses two metabolic pathways, with either high or low affinity for the substrate. The third adds excretion of fermentative products to the pathways in model two. Examining the steady states at various dilution rates (D) reveals a critical value (threshold value, Dc), at which the substrate can abruptly invade the cells. If the substrate or its derivatives are active, this abrupt concentration increase may act as a signal at particular growth rates. The second model has been used to study cases where the extracellular compound is a limiting substrate. When part of the substrate was excreted in the form of metabolites, there was a sharp transition between the anabolic and excretion pathways. The excretion pathways are abruptly activated above a critical growth rate. In all cases, the “threshold effects” were related to global and intrinsic characteristics of the culture, represented by the formula . This result may be of practical importance for designing and optimizing biotechnological processes in continuous cultures. The derived model has been effectively used to describe the Crabtree effect in Saccharomyces cerevisiae, which likely implies at least two input pathways of the substrate. The weak affinity pathway is responsible for the respiratory-reproductive transition and leads to the excretion of the fermentation products, including ethanol in yeast and lactate for certain cancers. Key words: Threshold, metabolic switch, Crabtree effect, substrate transport, respiro-fermentative transition.
Highlights
The interest of modeling in biotechnology is well established and the field of research has been developed considerably in an attempt to meet an unceasingly growing need (FOCAPD, 2004)
The structured models, which take into account various details concerning the physiological organization of the cell, provide a local description that allows for the representation of more complex phenomena
The rate resulting from these three processes will be referred to as transport/metabolism (T/M)
Summary
The interest of modeling in biotechnology is well established and the field of research has been developed considerably in an attempt to meet an unceasingly growing need (sometimes related with Biosystems) (FOCAPD, 2004). The structured models, which take into account various details concerning the physiological organization of the cell, provide a local description that allows for the representation of more complex phenomena. These models remain imprecise in terms of intracellular dynamics. The main objection concerning the latter two types of modeling relates to the way these models highlight the regulation of metabolism They call upon very general optimization concepts, such as growth rate maximization (Giuseppin and van Riel, 2000), the legitimacy of which is not necessarily recognized (Varma and Palsson, 1993a, 1993b). The “modelbuilder” must introduce some conditional tests in his or her algorithm and choose the option that best corresponds to the “pre-established” optimization criterion
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