The discovery of moriniafungin, a novel sordarin derivative produced by Morinia pestalozzioides

被引:25
作者
Basilio, A
Justice, M
Harris, G
Bills, G
Collado, J
de la Cruz, M
Diez, MT
Hernandez, P
Liberator, P
Kahn, JN
Pelaez, F
Platas, G
Schmatz, D
Shastry, M
Tormo, JR
Andersen, GR
Vicente, F
机构
[1] Merck Sharp & Dohme Espana, Merck Res Labs, Ctr Invest Bas, Madrid 28027, Spain
[2] Merck Res Labs, Rahway, NJ 07065 USA
[3] Aarhus Univ, Dept Mol Biol, DK-8000 Aarhus, Denmark
关键词
antifungal compound; sordarin; Morinia; fungal protein synthesis; natural products; taxonomy;
D O I
10.1016/j.bmc.2005.08.046
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
A novel sordarin derivative, moriniafungin (1), containing a 2-hydroxysebacic acid residue linked to C-3' of the sordarose residue of sordarin through a 1,3-dioxolan-4-one ring was isolated from the fungus Morinia pestalozzioides. Isolation of moriniafungin employed a highly specific bioassay consisting of a panel of Saccharomyces cerevisiae strains containing chimeric eEF2 for Candida glabrata, Candida krusei, Candida lusitaniae, Crytpococcus neoformans, and Aspergillus fumigates as well as wild type and human eEF2. Moriniafungin exhibited an MIC of 6 mu g/mL versus Candida albicans and IC50's ranging from 0.9 to 70 mu g/mL against a panel of clinically relevant Candida strains. Moriniafungin was shown to inhibit in vitro translation in the chimeric S. cerevisae strains at levels consistent with the observed IC50. Moriniafungin has the broadest antifungal spectrum and most potent activity of any natural sordarin analog identified to date. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:560 / 566
页数:7
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