In a particle containing medium, the kinetics of formation of secondary metabolites of a Streptomyces wild type and a mutant strain were determined by spectrophotometric measurements of the anthracyclinone pigments and by the analysis of antibiotic activity of the substances produced. The results were related to the physiological state of the culture derived from the oxygen supply.
The total cultivation time was about 400 hours. The production of secondary metabolites started at the end of the logarithmic growth phase (after about 30 hours). During the following cultivation remarkable differences between the two strains regarding the formation of pigments and antibiotics occurred. In the wild type strain producing daunomycinone glycosides and related compounds with antibiotic activity, these antibiotics are active as inhibitors (negative feedback). Therefore, at a certain concentration of antibiotics, the de-novo formation of anthracycline molecules was impaired. In the mutant strain, as the result of a genetic change, the secondary metabolite production was shifted to nonglycosylated compounds. The production of these substances is not influenced by feedback inhibition as in the case of the wild type strain. From that reason the amount of pigment increased slightly throughout the course of the experiment.
Under our experimental conditions the measurement of oxygen supply was a suitable indicator of the physiological state of culture.