ANTHRACYCLINES - ISOLATION OF OVERPRODUCING STRAINS BY THE SELECTION AND GENETIC-RECOMBINATION OF PUTATIVE REGULATORY MUTANTS OF STREPTOMYCES-PEUCETIUS VAR. CAESIUS

In Streptomyces peucetius var. caesius, the production of anthracyclin es was suppressed either by 330 mM D-glucose or 25 mM phosphate. In ad dition, the anthracycline doxorubicin and the glucose analogue 2-deoxy glucose inhibited the growth of this microorganism at concentrations o f 0.025 mM and 10 mM respectively. Spontaneous and induced mutants, re sistant to the action of these compounds, were isolated, tested and ch osen by their ability to overproduce anthracyclines. Genetic recombina tion between representative mutants was carried out by the protoplast fusion technique. Some recombinants carrying resistance to doxorubicin : phosphate and 2-deoxyglucose produced more than 40-fold greater leve ls of anthracyclines than those obtained with the parental strain. Thi s improvement resulted in total antibiotic titres of more than 2 g/l c ulture medium at 6 days of fermentation.