OPTIMAL PRODUCTION OF GLUTATHIONE BY CONTROLLING THE SPECIFIC GROWTH RATE OF YEAST IN FED-BATCH CULTURE

Abstract

The optimal profile of the specific growth rate was obtained utilizing simple mathematical model in the yeast fed-batch culture. The model was built based on the mass balance around the fed-batch system and relationship between the specific growth rate, μ, and the specific production rate of glutathione, ρG. Optimal profile of μ was calculated as a bang-bang type one. That is, μ should start from the maximum value, μmax and should be kept at μmax. And then μ should be switched to μC, that gives a maximum value of ρG. It has been proved from the maximum principle that switching was once and switching time from μmax to μC depended on the final required glutathione concentration in the cell. Finally, this ideal profile of μ for the maximum production of glutathione was realized by manipulating the substrate feed rate, and μ could be controlled at the optimal profile given in advance, using the extended Kalman filter and PF(Programmed Controller/ Feedback Compensator) System. As the result, the maximum production of glutathione was accomplished successfully. The control strategy employed here can be applied to the other batch reaction processes.