Mechanism of action of monoketo-organomycin, cystaurimycin and their performic acid-oxidized modifications. I. Effects on bacterial growth and ribosomal peptidyl transferase activity.

Abstract

The response of 15 bacterial cultures to the inhibitory effects of the above mentioned compounds was investigated. These varied considerably. Escherichia coli cultures resistant to the compounds tested showed that monoketo-organomycin and cystaurimycin inhibit bacterial growth by what appears to be the one and same mechanism which is not the same as that exhibited by their performic acid-oxidized modifications. This was confirmed by using cell free extracts of E. coli. In light of the puromycin reaction, using chloramphenicol and chlorotetracycline as control inhibitors, monoketo-organomycin and cystaurimycin were found to inhibit protein synthesis in vitro by inhibiting peptidyl transferase of ribosomes. In marked contrast, this enzyme was activated, as also was protein synthesis, by their performic acid-oxidized modifications. It was thus suggested that the growth inhibitory effects of the latter compounds might be due to their interference in other metabolic activities of the above test organism. The results obtained are discussed in light of the chemical similarities or differences existing between the compounds investigated.