Divalent metal ion catalysis of the oxidation of rifamycin SV to refamycin S

The antibiotic, rifamycin SV, has been characterized as a potent inhibitor of the initiation of RNA synthesis by certain prokaryotic RNA polymerases [ 1 ] . The characteristics of inhibition by rifamycin SV resemble those described for the chelating agent, 1: IO-phenanthroline [2], and binding studies indicate that both these inhibitors specifically prevent the low affinity interaction of prokaryotic RNA polymerase with purine nucleotides which occurs in the absence of added divalent metal ions [3]. Since prokaryotic RNA polymerase has been shown to be a zinc metalloenzyme [2], it seemed possible that inhibition by both rifamycin SV and 1: lo-phenanthroline might result from interaction with the bound metal ion. During EPR studies designed to measure the affinity of rifamycin SV for Mn” it was noted that the colour of the test solutions changed from yellow to deep red during the period of observation. Since this colour change appeared dependent on addition of Mn”, further studies were performed to elucidate the nature of the effect. These studies have shown that certain divalent metal ions are effective catalysts of the oxidation of rifamycin SV to rifamycin S. The effect may explain the previous report that rifamycin SV is unstable in solution and undergoes spontaneous oxidation to rifamycin S [4].