Maximum Production in Batch Culture of S. Cerevisiae Using Temperature-Dependent Gene Expression System

Abstract

A method for obtaining maximum production of the bioproduct in batch cultures is explained, and its validity is demonstrated by experimental data. The approach is based on a model which describes the relationship between the specific production rate, ρ, and specific growth rate,μ. Using a mathematical model, an optimal profile of the specific growth rate could then be obtained easily by the Maximum Principle. In most simple cases such as a linear relationship between μ. and ρ exists, the optimal profile of n becomes a boundary control so called bang-bang control and it can be interpreted as a two-stage production process composed of cell growth phase and production phase. Finally, the optimal profile was realized by changing the cultivation temperature in batch culture. Practical examples of bioproduction in Saccharomyces cercvisiae, such as acid phosphatase accumulated in the membrane and rice-α-amylase secreted which were produced by the recombinant gene expression due to the cultivation temperature shift up and down, showed that the two-stage production process could be realized experimentally, thus demonstrating the validity of the method.