Abstract
Abstract Pichia pastoris has been widely used as a host for the expression of heterologous proteins. This paper deals with the glycerol and methanol optimal feeding control in the cultivation of P. pastoris expressing recombinant human serum albumin. An earlier proposed macrokinetic model and a cell cycle model were used to determine the substrate feeding profiles. In the glycerol growth phase, the goal of substrate feeding control is to obtain high cell density as well as the desired level of the fraction of budding cells, while in the methanol growth phase, the goal of substrate feeding is to control the specific growth rate at various set-points. The effect of both glycerol and methanol feeding control strategies were evaluated experimentally. It was found that the productivity may be enhanced if the fraction of budding cells at the end of the glycerol growth phase is minimized and if the specific growth rate during the methanol phase controlled between 0.005 and 0.006 h-1.
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