Munumbicins, wide-spectrum antibiotics produced by Streptomyces NRRL 30562, endophytic on Kennedia nigriscans

Dept of Plant Sciences, Montana State University, Bozeman, MT 59717, USA 1 Dept of Botany and Range Sciences 2 and Dept of Microbiology 3 , Brigham Young University, Provo, UT 84602, USA Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA 4 Infectious Diseases Section, Veterans Affairs Medical Center, 500 West Fort St, Boise, ID 83702 and Dept of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA 5 Novozymes Biotech Inc., 1445 Drew Ave, Davis, CA 95616, USA 6 Author for correspondence: Gary Strobel. Tel: +1 406 994 5148. Fax: +1 406 994 7600. e-mail: uplgs{at}montana.edu Munumbicins A, B, C and D are newly described antibiotics with a wide spectrum of activity against many human as well as plant pathogenic fungi and bacteria, and a Plasmodium sp. These compounds were obtained from Streptomyces NRRL 3052, which is endophytic in the medicinal plant snakevine ( Kennedia nigriscans ), native to the Northern Territory of Australia. This endophyte was cultured, the broth was extracted with an organic solvent and the contents of the residue were purified by bioassay-guided HPLC. The major components were four functionalized peptides with masses of 1269·6, 1298·5, 1312·5 and 1326·5 Da. Numerous other related compounds possessing bioactivity, with differing masses, were also present in the culture broth extract in lower quantities. With few exceptions, the peptide portion of each component contained only the common amino acids threonine, aspartic acid (or asparagine), glutamic acid (or glutamine), valine and proline, in varying ratios. The munumbicins possessed widely differing biological activities depending upon the target organism. For instance, munumbicin B had an MIC of 2·5 µg ml -1 against a methicillin-resistant strain of Staphylococcus aureus , whereas munumbicin A was not active against this organism. In general, the munumbicins demonstrated activity against Gram-positive bacteria such as Bacillus anthracis and multidrug-resistant Mycobacterium tuberculosis . However, the most impressive biological activity of any of the munumbicins was that of munumbicin D against the malarial parasite Plasmodium falciparum , having an IC 50 of 4·5±0·07 ng ml -1 . This report also describes the potential of the munumbicins in medicine and agriculture. Keywords: endophyte, actinomycete, malaria, tuberculosis, biological control Abbreviations: COSY, correlated spectroscopy a The GenBank accession number for the sequence