Scale-down of continuous protein producing Saccharomyces cerevisiae cultivations using a two compartment system

In the biotechnological industry, economic decisions in investment are typically based on laboratory scale experiments. Scale-down as a tool is therefore of high industrial importance in order to transfer the processes into larger production scale without loss in performance. In this study large scale prolonged continuous cultivations with a heterologous protein producing Saccharomyces cerevisiae strain have been scaled-down to a two compartment scale-down reactor system. The effects of glucose, pH, and oxygen concentration gradients have been investigated by comparison with corresponding 300 ml standard continuous cultivations. It was found that substrate gradients within a limited range result in increased productivity of the heterologous protein under regulation of the glycolytic TPI promoter and delay the decrease of protein and trehalose production during continuous cultivation. Based on these results, it is argued that introduction of variations in substrate concentration can be beneficial for industrial continuous cultivations.