Maximum histidine production by fed-batch culture of Brevibacterium flavum

Abstract

In this paper, an approach for the maximum production of histidine in fed-batch culture was proposed and its validity was shown from the experimental data. The approach was based on the model which describes the relationship between specific production rate, π, and specific growth rate, μ. Using a mathematical model, an optimal profile of the specific growth rate could be obtained easily by the Maximum Principle. Finally, the optimal profile was realized by changing the feed rate of substrate in a practical fed-batch culture. The maximum production of histidine could be attained by this procedure. The specific histidine production rate, π H, had the maximum at a certain specific growth rate, μ C, and the optimal profile was obtained as the bang-bang control (boundary control). That is, in the early stage of the fed-batch culture μ should be kept at its maximum value, μ max and for the next stage μ should be kept at μ C. The control strategy can be comprehended as a two-stage production procedure composed of a cell growth stage and then a production stage. The two-stage production process of histidine could be realized experimentally and the validity of the proposed method was shown.