Kakadumycins, novel antibiotics fromStreptomycessp. NRRL 30566, an endophyte ofGrevillea pteridifolia

Abstract

An endophytic streptomycete (NRRL 30566) is described and partially characterized from a fern-leaved grevillea (Grevillea pteridifolia) tree growing in the Northern Territory of Australia. This endophytic streptomycete produces, in culture, novel antibiotics - the kakadumycins. Methods are outlined for the production and chemical characterization of kakadumycin A and related compounds. This antibiotic is structurally related to a quinoxaline antibiotic, echinomycin. Each contains, by virtue of their amino acid compositions, alanine, serine and an unknown amino acid. Other biological, spectral and chromatographic differences between these two compounds occur and are given. Kakadumycin A has wide spectrum antibiotic activity, especially against Gram-positive bacteria, and it generally displays better bioactivity than echinomycin. For instance, against Bacillus anthracis strains, kakadumycin A has minimum inhibitory concentrations of 0.2-0.3 microg x ml(-1) in contrast to echinomycin at 1.0-1.2 microg x ml(-1). Both echinomycin and kakadumycin A have impressive activity against the malarial parasite Plasmodium falciparum with LD(50)s in the range of 7-10 ng x ml(-1). In macromolecular synthesis assays both kakadumycin A and echinomycin have similar effects on the inhibition of RNA synthesis. It appears that the endophytic Streptomyces sp. offer some promise for the discovery of novel antibiotics with pharmacological potential.

Isolation and antimicrobial activities of actinobacteria closely associated with liquorice plants Glycyrrhiza glabra L. and Glycyrrhiza inflate BAT. in Xinjiang, China

“…Actinobacterial endophytes of terrestrial and marine plants are considered potential sources of novel secondary metabolites (Bascom-Slack et al, 2009;Castillo et al, 2003Castillo et al, , 2007Liu et al, 2014;Strobel et al, 2004). Most of the Streptomyces strains isolated in this study showed antimicrobial activity against a broad range of indicator organisms, which usually cause serious losses in agricultural production.…”

Natural Products from Plant-Associated Microorganisms: Distribution, Structural Diversity, Bioactivity, and Implications of Their Occurrence

“…(ATCC 74360), a fungus endophytic in Juniperus communis. 41 The interesting antifungal spectrum exhibited by 66 and its effect on morphology of Aspergillus fumigatus, which was shown to be comparable to that of the glucan synthase inhibitor, pneumocandin B 0 [the natural precursor of the clinical candidate MK-0991 (caspofungin acetate)], has led to an extensive search for other Hormonema isolates from different geographic locations and hosts for enfumafungin (66). Of the 53 isolates screened, antifungal activity was detected in five strains, but by HPLC analysis only two of them were found to produce 66, in amounts similar to the strain ATCC 74360.…”

Phylogenetic Characterization of Culturable Antibiotic Producing Streptomyces from Rhizospheric Soils

“…Streptomyces spp. NRRL 30566 was reported to produced a novel antibiotic, kakadumycins which are DNA intercalating antibiotics that act by inhibiting DNA directed enzymatic RNA synthesis [50]. A novel compound Faeriefungin (polyene macrolides), was isolated from S. griseus, it was reported to have antibacterial, antifungal and insecticidal activities [51].…”