Inhibition of bacterial RNA polymerase by the cyanobacterial metabolites 12-epi-hapalindole E isonitrile and calothrixin A

The alkaloid 12-epi-hapalindole E isonitrile, from a cyanobacterial Fischer ella species, and the indolophenanthridine calothrixin A, from Calothrix, i nhibited Escherichia coli RNA polymerase competitively with respect to ATP, and non-competitively with respect to UTP. The inhibition was dependent on the order of addition of the inhibitors. The K-I values, with ATP as the v ariable substrate, were 1.3 +/- 0.2 mM and 0.23 +/- 0.11 mM, respectively. Based on comparisons with the sensitivity of whole cells to these inhibitor s: it is concluded that other targets in addition to RNA polymerase may als o be implicated in their action. (C) 2001 Federation of European Microbiolo gical Societies. Published by Elsevier Science B.V. All rights reserved.