Development of high-cell-density fermentation for heterologous interleukin 1 beta production in Kluyveromyces lactis controlled by the PHO5 promoter.

The use of a phosphate organic form taken up by Kluyveromyces lactis removes repression of the PHO5 promoter and releases heterologous interleukin 1 beta synthesis while providing sufficient phosphate for growth. The oxidative metabolism of high-cell-density fed-batch and chemostat cultures was thus maintained under derepressed protein synthesis conditions. Interleukin 1 beta production was then growth-associated, an unusual mode of protein synthesis regulation under the control of the PHO5 promoter.