CYBERNETIC MODELING OF THE GROWTH OF MICROORGANISMS IN MULTIPLE SUBSTRATE ENVIRONMENTS
Abstract
The metabolic activities exhibited by microorganisms in a multiple substrate environment vary from the preferential utilization of a specific substrate to the simultaneous consumption of all substrates. A cybernetic framework is presented which views the microbial response to be a consequence of an "optimal" regulatory strategy. The model cell within the lumped biophase is assumed to consist of three main components: an adaptive machinery concerned with the synthesis of key proteins for the utilization of specific substrates; a permanent machinery consisting of metabolic activities that are not directly related to the adaptive process; and a regulator which guides the cellular response by a judicious allocation of intracellular resources in actuating the synthesis of key proteins for the appropriate substrates. A mathematical model is developed within the cybernetic framework for the batch aerobic growth of Klebsiella pneumoniae on a mixture of D-glucose and D-xylose. A single critical resource is allocated according to an objective function that embodies the regulatory repertoire persumably acquired by the cells as a result of the competition for scarce resources during their evolutionary history. The optimal solution obtained by using Calculus of Variations turns out to be a "bang-bang" type of control policy. The model solution describes well the experimental observations for diauxic growth of Klebsiella pneumoniae obtained using a fermentor coupled to an Apple-II Plus microcomputer. Striking variations in oxygen uptake are observed experimentally during the switching of the cell's adaptive machinery for the utilization of the less preferred substrate. The observed dissolved oxygen response is shown to be a sensitive monitor of the rapidly changing adaptive machinery within the cell. Cell mass and off-gas CO(,2) and O(,2) levels were also monitored. Other experimental systems investigated to elucidate cellular strategies in mixed substrate systems include binary combinations of the following carbon substrates: D-glucose, D-xylose, L-arabinose, lactose and citrate. Perturbed batch experiments with intermittent pulsed switching provide further insight into the cellular strategies.
Degree
Ph.D.
Subject Area
Chemical engineering
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