Chlorination Inhibitors in Streptomyces aureofaciens

IN a Belgian patent 1 granted to Spofa (Czechoslovakia) a number of pyrimidines chlorinated in the 2 position were reported to be active in inhibiting halogenation in the biosynthesis of chlortetracycline resulting instead in the production of high concentrations of tetracycline. It was of interest to us to test such compounds in the Streptomyces aureofaciens BC -41 system we have used before 2 . The two antibiotics were determined spectro-photometrically, taking advantage of their differential degradation rates in acid and alkaline solution. Compared with tetracycline, chlortetracycline is relatively stable to acid and unstable to base. Selected results were confirmed by paper chromatography. In the course of these trials, in which some thirty halogenated pyrimidines and related heterocycles were tested, very few were found to show activity. The most active compound was found to be 2,4-dichloro-5-methyl pyrimidine which, when added to the medium in a concentration of 10 p.p.m., resulted in the production of 80–95 per cent tetracycline in the final broth, confirming in part the work reported in the Belgian patent 1 . Closely related pyrimidines were either much less or not at all active for our strain BC -41. This is shown in Table 1.