An Engineering Study of Metabolic Regulation in Microbial Processes

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Reaction kinetic models to which cybernetic variables (calculated using simple macroeconomic principles) have been added to represent the internal regulation of the syntheses and activities of key enzymes for competing metabolic processes are shown to successfully describe a variety of growth situations in mixed (substitutable) substrate systems. A dynamically evolving cybernetic framework is presented for modeling metabolic regulation in which transport, reaction, and product formation compete for cellular material and energy resources with evidence that observations on abrupt switches in metabolic pathways, metabolic lags, exotic (oscillatory) dynamics, etc., can all be accommodated by these models. A program is on-going which will provide detailed observations of enzyme levels, cell mass, biotic and abiotic substrate, and product concentrations, etc., which will be compared with model predictions under various situations. These situations include different patterned changes in the abiotic phase in fed batch and continuous cultures. Microorganisms respond to their environment in ways that are controlled by a very elaborate and complex internal mechanism mediated by important molecules of the cell, such as DNA, RNA, and many others. In modeling microbial processes responsible for the many products of biotechnology, account must be made of such metabolic regulation. Evidence is present from past work that metabolic regulation can be described simply using macroeconomic principles. An extensive research program is now developing various aspects of this idea in modeling processes important to modern biotechnology.