Development of a chemically defined medium for the production of the antibiotic platensimycin by Streptomyces platensis.

The actinomycete Streptomyces platensis produces two compounds that display antibacterial activity: platensimycin and platencin. These compounds were discovered by the Merck Research Laboratories, and a complex insoluble production medium was reported. We have used this medium as our starting point in our studies. In a previous study, we developed a semi-defined production medium, i.e., PM5. In the present studies, by varying the concentration of the components of PM5, we were able to develop a superior semi-defined medium, i.e., PM6, which contains a higher concentration of lactose. Versions of PM6, containing lower concentrations of all components, were also found to be superior to PM5. The new semi-defined production media contain dextrin, lactose, MOPS buffer, and ammonium sulfate in different concentrations. We determined antibiotic production capabilities using agar diffusion assays and chemical assays via thin-layer silica chromatography and high-performance liquid chromatography. We reduced crude nutrient carryover from the seed medium by washing the cells with distilled water. Using these semi-defined media, we determined that addition of the semi-defined component soluble starch stimulated antibiotic production and that it and dextrin could both be replaced with glucose, resulting in the chemically defined medium, PM7.

Development of a semi-defined medium supporting production of platensimycin and platencin by Streptomyces platensis.

Platensimycin and platencin are compounds that were discovered at Merck Research Laboratories and have shown promising antibacterial activity. They are both produced in fermentation by the actinomycete Streptomyces platensis. Merck reported a crude, insoluble production medium to produce the antibiotics. To test the possible effects of different primary metabolites and inorganic compounds on the production of these antibiotics, a chemically-defined medium is needed. The effects that these compounds have on production could provide information about the precursors and biosynthetic pathway of the antibiotics. We have tested and developed a number of media with varying degrees of chemical definition and solubility using the Merck medium as our starting point. Our latest production medium, PM5, is soluble and semi-defined. It yields suitable production of the compounds, as shown by agar diffusion assays, bioautography and HPLC. The antibiotics were located in the extracellular broths and not in the mycelia.