Kakadumycins, novel antibiotics from Streptomyces sp NRRL 30566, an endophyte of Grevillea pteridifolia

被引:129
作者
Castillo, U
Harper, JK
Strobel, GA [1 ]
Sears, J
Alesi, K
Ford, E
Lin, J
Hunter, M
Maranta, M
Ge, HY
Yaver, D
Jensen, JB
Porter, H
Robison, R
Millar, D
Hess, WM
Condron, M
Teplow, D
机构
[1] Montana State Univ, Dept Plant Sci, Bozeman, MT 59717 USA
[2] Montana State Univ, Dept Chem, Bozeman, MT 59717 USA
[3] Novozymes Biotech Inc, Davis, CA 95616 USA
[4] Brigham Young Univ, Dept Mol Biol & Microbiol, Provo, UT 84602 USA
[5] Brigham Young Univ, Dept Integrat Biol, Provo, UT 84602 USA
[6] Brigham & Womens Hosp, Boston, MA 02115 USA
[7] Harvard Univ, Sch Med, Boston, MA 02115 USA
基金
美国国家科学基金会;
关键词
streptomycete; malaria; endophyte; tandem mass spectrometry; anthrax; DNA;
D O I
10.1016/S0378-1097(03)00426-9
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 mug ml(-1) in contrast to echinomycin at 1.0-1.2 mug ml(-1). Both echinomycin and kakadumycin A have impressive activity against the malarial parasite Plasmotliumfulciparum with LD(50)s in the range of 7-10 ng 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. (C) 2003 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码:183 / 190
页数:8
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