Munumbicins, wide-spectrum antibiotics produced by Streptomyces NRRL 30562, endophytic on Kennedia nigriscans.
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 microg x 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 x ml(-1). This report also describes the potential of the munumbicins in medicine and agriculture.
Castillo
Uvidelio F
UF
Dept of Plant Sciences, Montana State University, Bozeman, MT 59717, USA1.
Strobel
Gary A
GA
Dept of Plant Sciences, Montana State University, Bozeman, MT 59717, USA1.
Ford
Eugene J
EJ
Dept of Plant Sciences, Montana State University, Bozeman, MT 59717, USA1.
Hess
Wilford M
WM
Dept of Botany and Range Sciences2 and Dept of Microbiology3, Brigham Young University, Provo, UT 84602, USA.
Porter
Heidi
H
Dept of Botany and Range Sciences2 and Dept of Microbiology3, Brigham Young University, Provo, UT 84602, USA.
Jensen
James B
JB
Dept of Botany and Range Sciences2 and Dept of Microbiology3, Brigham Young University, Provo, UT 84602, USA.
Albert
Heather
H
Dept of Botany and Range Sciences2 and Dept of Microbiology3, Brigham Young University, Provo, UT 84602, USA.
Robison
Richard
R
Dept of Botany and Range Sciences2 and Dept of Microbiology3, Brigham Young University, Provo, UT 84602, USA.
Condron
Margret A M
MAM
Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA4.
Teplow
David B
DB
Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA4.
Stevens
Dennis
D
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, USA5.
Yaver
Debbie
D
Novozymes Biotech Inc., 1445 Drew Ave, Davis, CA 95616, USA6.
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004353:Drug Evaluation, Preclinical; D007887:Fabaceae / Q000382:microbiology; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D019906:Nuclear Magnetic Resonance, Biomolecular; D010961:Plasmodium / Q000187:drug effects; D013302:Streptomyces / Q000737:chemistry*
D000596:Amino Acids; D000900:Anti-Bacterial Agents