Theoretical analysis of effects of metabolic overflow and time delay on the performance and dynamic behavior of a two-stage fermentation process

The performance and dynamic behavior of a two-stage fermentation process are studied for continuous cultivation of microorganisms with metabolic overflow, the growth of which is subject to inhibitions of substrate and product. Metabolic overflow of product and its inhibition of cell growth lead to multiplicity, in which a steady state with higher biomass or product concentrations can be obtained by operating the bioreactor under certain conditions. For instance, a high density cell cultivation should be carried out by increasing the initial concentration of substrate in feed at a constant dilution rate. In contrast, a high yield of target product to substrate could be obtained by decreasing the initial concentration of substrate in feed. If a time delay between biomass formation and the change of the operation conditions is higher than a critical value, persistent periodical oscillations would occur. The critical time delay is dependent on the operating conditions, i.e. the initial substrate concentration and dilution rate. It is very large when the initial concentration of substrate is relatively low or high at a constant dilution rate. A two-stage fermentation process in terms of dynamic behavior is more efficient than one stage fermentation in steady state. The bioreactor performance, e.g. substrate consumption, product concentration, yield of product from substrate, and productivity, can be improved by using self-sustained oscillations in a system of two bioreactors in series. (C) 2002 Elsevier Science B.V. All rights reserved.