Autonomous selection of differentiation mutants of Streptomyces lividans TK24 in continuous culture

Summary Streptomyces lividans TK24 strains transformed with different recombinat derivatives of the vector plasmid pIJ487 were continuously cultivated in a chemostat. The first plasmid derivative contained the determinant for human interferon-alpha-1 (IFN) and the expression-secretion-unit (ESU) for this protein. In the second one a nourseothricin resistance determinant (ntc) was inserted additionally. The chemostat operated mainly at glucose limitation and low dilution rates. The structural and functional stabilities of the plasmids were shown to depend on the selection pressure. The host mutants enriched in the chemostat differed from the parental strain with respect to the growth pattern of aerial and submerged mycelium, the spore formation, and the formation and secretion of pigments and enzymes. Some highly stable host-vector systems could be selected. The plasmids' genotype influenced the growth pattern of the host mutants enriched in the chemostat in dependence on the limitation conditions as well as the stability of plasmid inheritance, plasmid structure and pigment formation in these mutants.