Methanol induction strategy using the two-loop control-based DO-stat and its application to repeated induction in methylotrophic yeast Pichia pastoris

A simple control strategy of DO-stat was introduced to the recombinant rGuamerin production process in Pichia pastoris. This induction strategy consisted of two interrelated control loops ‘by which oxygen ratio of inlet gas and methanol feeding rate was controlled. Using this control strategy, over-feeding or under-feeding of methanol could be avoided in concomitance with the efficient control of dissolved oxygen level. As a result, the cell concentration reached 130 g/L and rGuamerin expression level was 450 iu/L, which was more than 40% increased result comparing with the fed-batch process using manual control of methanol feeding rate.