Strain Degeneration in Industrial Streptomycetes
Daslav Hranueli*, Birgit Gravius**, Tajana Bezmalinović*, Anja Eichner** and J. Cullum**
*PLIVA d.d,, Research Institute, 41000 Zagreb, Republic of Croatia
**LB Genetik, Universität Kaiserslautern, D-67653 Kaiserslautern, F. R. G.
Received August 30, 1994
Accepted December 22, 1994
Strain degeneration in wide-spread in industrial Streptomycetes strains and describes a variety of spontaneous changes that result in deleterious phenotypes especially for antibiotic yield. Genetic instability (i.e. the occurrence of spontaneous mutations with a high frequency) is common in Streptomyces strains and has been studied in several model systems, where a pattern of large-scale DNA deletions and amplifications has been established. However, little work has been performed with high-yielding industrial strains to define the relationship between strain degeneration and genetic instability. Some S. riniosus R6 strains that have been selected for high oxytetracycline production show genetic instability. Two classes of mutants were defined with reduced or no antibiotic production. The Class II mutants carried large deletions including the oxylctracycline gene cluster, which resulted in the loss of both the production and resistance genes. Although this proves that the genes lie in an unstable chromosomal region, the fact that the mutants are sensitive to oxytetracycline makes them important for strain degeneration. In contrast, the commonest low-producing mutants (Class I) remained resistant to the antibiotic and outgrew the parent strain in competition experiments. This suggests that the Class I mutants, which did not show any delectable DNA rearrangements, are responsible for strain degeneration. A hypothesis to explain Class I mutants will be discussed.
Presented at the 2nd Croatian Congress of Food Technologists, Biotechnologists and Nutritionists, Zagreb, June15-17,1994