Modeling and optimization of alpha-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 th e efficiency of cell cycle population control. First, the effects of-the gl ucose 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 w ere then estimated. The proposed model was shown to be applicable for unbal anced as well as balanced growth phases. The optimal control strategy in re spect of temperature and glucose concentration for maximum rice alpha-amyla se production, taking into account the cell cycle population, was determine d and the result was compared with that obtained by a simple mathematical m odel in which cell cycle distribution was not considered. Finally, the effe ct of the initial population of each cell cycle phase on the final amount o f the product under optimal operational conditions was investigated. The si mulation and experimental data coincided well with each other, and the mode l was used to optimize the control strategy for maximum alpha-amylase produ ction. (C) 1999 Elsevier Science B.V. All rights reserved.