Munumbicins E-4 and E-5: novel broad-spectrum antibiotics from<i>Streptomyces</i>NRRL 3052

Streptomyces NRRL 30562 was originally isolated as an endophyte from Kennedia nigriscans, snakevine, in the Northern Territory of Australia. This plant has been used for centuries by Aboriginal peoples to treat open bleeding wounds to prevent sepsis. A solvent extract of the crude fluid from cultures of this endophyte possesses wide-spectrum antibiotic activity. Some of the bioactivity is associated with the appearance of actinomycins X2, D, and Xobeta, the first two of which had been previously designated munumbicins A and B, respectively. Other novel compounds bearing wide-spectrum antibiotic activity are also produced by Streptomyces NRRL 30562, and these are designated munumbicins E-4 and E-5. Mass spectrometric analyses of these peptide antibiotics show that they have identical masses (1445.00) but different retention times on HPLC. Both compounds showed activity against gram-positive and gram-negative bacteria. The plant pathogenic fungus, Pythium ultimum is sensitive to both munumbicins at 5.0 microg mL(-1) The malarial parasite, Plasmodium falciparum has IC50 values of 0.50+/-0.08 and 0.87+/-0.0.26 microg mL(-1) for E-4 and E-5, respectively. It appears that other bioactive compounds, related to E-4 and E-5, are also produced making it the most biologically active endophytic Streptomyces spp. on record.