Kribellosides, novel RNA 5′-triphosphatase inhibitors from the rare actinomycete Kribbella sp. MI481-42F6

Abstract

Yeast capping enzymes differ greatly from those of mammalian, both structurally and mechanistically. Yeast-type capping enzyme repressors are therefore candidate antifungal drugs. The 5ʹ-guanine-N7 cap structure of mRNAs are an essential feature of all eukaryotic organisms examined to date and is the first co-transcriptional modification of cellular pre-messenger RNA. Inhibitors of the RNA 5ʹ-triphosphatase in yeast are likely to show fungicidal effects against pathogenic yeast such as Candida. We discovered a new RNA 5ʹ-triphosphatase inhibitor, designated as the kribellosides, by screening metabolites from actinomycetes. Kribellosides belong to the alkyl glyceryl ethers. These novel compounds inhibit the activity of Cet1p (RNA 5ʹ-triphosphatase) from Saccharomyces cerevisiae in vitro with IC 50 s of 5-8 μM and show antifungal activity with MICs ranging from 3.12 to 100 μg ml À1 against S. cerevisiae.

Marine Rare Actinomycetes: A Promising Source of Structurally Diverse and Unique Novel Natural Products

“…Interestingly, novel kribellosides from a marine Kribbella sp. inhibit activity of Cet1p (RNA 5’-triphosphatase) from Saccharomyces cerevisiae in vitro [208]. Another interesting biological activity is anti-allergic activity shown by nesterenkoniane, a novel cyclic ether isolated from the deep-sea-derived Nesterenkonia flava .…”

The secondary metabolites of rare actinomycetes: chemistry and bioactivity

“…Two new metabolites, nonomuric acid (100) and 3-hydroxy deoxydaunorubicinol aglycone (101), together with two known compounds, 3-rhodomycinone (102) and 7-deoxy-13dihydrocarminomycinone (103), were separated from Nonomuraea rhodomycinica NR4-ASC07 from soil from the Sirindhorn peat swamp forest. Compounds 100 and 102 displayed antimalarial activity, and their IC 50 values were 8.00 and 8.88 mg mL À1 , respectively.…”

Novel South African Rare Actinomycete Kribbella speibonae Strain SK5: A Prolific Producer of Hydroxamate Siderophores Including New Dehydroxylated Congeners

“…Species of the genus Kribbella are classified as rare actinomycetes since they are less frequently isolated than species of other actinomycete genera, especially Streptomyces, although they may not be rare in the environment [14]. Kribbella strains are rich sources of novel secondary metabolites; for example, the antifungal alkyl glyceryl ethers, kribelloside A-D, which are produced by Kribbella strain MI481-42F6, which was isolated from a soil sample collected in Japan [15]. Among the Kribbella species isolated, 31 have currently been fully characterized [16].…”