Modeling and optimization of α-amylase production in a recombinant yeast fed-batch culture taking account of the cell cycle population distribution

A simple mathematical model describing the cell cycle dependency of rice a-amylase production by a recombinant yeast was constructed to investigate the efficiency of cell cycle population control. First, the effects of-the glucose concentration and cultivation temperature on the specific growth rate, the specific production rate of rice alpha-amylase, and the distribution of the cell cycle population were studied under balanced growth conditions. On the basis of the results, parameter values for the mathematical model were then estimated. The proposed model was shown to be applicable for unbalanced as well as balanced growth phases. The optimal control strategy in respect of temperature and glucose concentration for maximum rice alpha-amylase production, taking into account the cell cycle population, was determined and the result was compared with that obtained by a simple mathematical model in which cell cycle distribution was not considered. Finally, the effect of the initial population of each cell cycle phase on the final amount of the product under optimal operational conditions was investigated. The simulation and experimental data coincided well with each other, and the model was used to optimize the control strategy for maximum alpha-amylase production. (C) 1999 Elsevier Science B.V. All rights reserved.