STABILITY OF RECOMBINANT PROTEIN-PRODUCTION BY PENICILLIUM-CHRYSOGENUM IN PROLONGED CHEMOSTAT CULTURE

A strain (WKW2) of Penicillium chrysogenum transformed with heterologo us fungal acetamidase (amdS) and bacterial beta-galactosidase (lacZ) w as grown at a dilution rate of 0.17 h(-1) (doubling time of approx. 4. 1 h) for 1600 h in a glucose-limited culture. By the end of the experi ment the original strain had been almost completely replaced by sponta neous, morphological mutants, but the acetamidase and beta-galactosida se activities of the culture were essentially unaltered. Furthermore, when WKW2 and the non-transformed parental strain (NRRL1951) were gown together in glucose- or NH4+-limited chemostat cultures, neither stra in had a selective advantage over the other. Thus, heterologous gene e xpression does not result in NRRL1951 having a selective advantage ove r WKW2. These results suggest that continuous flow culture systems cou ld be used for efficient (and cost effective) production of recombinan t proteins.