Biological function of gramicidin: selective inhibition of RNA polymerase

This paper describes a novel biochemical effect of gramicidin, a class of peptide antibiotics produced by Bacillus brevis during the transition from vegetative growth to sporulation. Gramicidin inhibits RNA synthesis by purified RNA polymerase (nucleosidetriphosphate:RNA nucleotidyl-transferase, EC 2.7.7.6) by interfering with the binding of RNA polymerase to DNA. This effect seems to involve the destabilization of the "open" RNA polymerase-DNA complex, a mode of action consistent with the control of promoter selection. Selectivity in the inhibition of RNA synthesis by gramicidin is observed when transcription is partially blocked by low levels of actinomycin D. Since the inhibition of RNA synthesis by gramicidin is obtained in a highly purified system devoid of membranes, it must be distinct from the ionophoretic activity of the antibiotic. It is possible that this new mode of action reflects the function of gramicidin during bacterial sporulation.