INFLUENCE OF CULTURE CONDITIONS ON THE PRODUCTION OF HETEROLOGOUS INTERLEUKIN-1-BETA BY KLUYVEROMYCES-LACTIS

Under the control of the repressible PHO5 promoter, the expression of gene encoding interleukin 1beta (I11beta) was derepressed when the med ium was depleted of free inorganic phosphate (Pi). Maximum heterologou s protein synthesis was obtained in the presence of 75 mg KH2PO4/l (fo r 20 g glucose/l). The successful heterologous protein production grea tly depends on nutritional culture conditions as I11beta production ef ficiency was increased by 83% through optimization of the growth mediu m. Comparison of different phosphate-limited cultivation strategies le d to the development of a batch culture procedure with nutrient pulses to delay induced oxido-fermentative glucose metabolism and increase t he I11beta production to 135 mg/l.