INVITED REVIEW ON THE USE OF CHEMICALLY STRUCTURED MODELS FOR BIOREACTORS

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Abstract
An individual cell is an immensely complicated self-regulated chemical reactor that can alter its biosynthetic machinery to meet the demands of a changing environment. The biochemical engineer must build a large macroscopic reactor to harness the cells for desirable chemical conversions. The design and control of such bioreactors would be facilitated with effective mathematical models of the response of the culture to changes in nutrients or other environmental variables. Because of the inherent internal plasticity of the cell, models must reflect the changing structure of the biomass. This paper reviews some examples of models which contain components representing various chemical fractions within the cell. The advantage of these models is their potential ability to predict the dynamic behavior of a cellular population. In addition such models are potential tools for testing hypotheses concerning cellular control mechanisms and consequently the development of more effective cell strains. Models of populations based on a finite-representation technique using an ensemble of chemically structured single-cell models are emphasized. These latter models are capable of accurate a priori prediction of bioreactors to perturbations in flow rates or feed concentrations. Models which aspire to the a priori quantitative prediction of cell population behavior must be sufficiently complex that shifts in growth-rate limiting processes can be taken into account; consequently a high-level of chemical structure will characterize the best models.