Search for new antifungal agent based on finding of biosynthetic pathway of novel glycosphingolipids

基于新型鞘糖脂生物合成途径的寻找新型抗真菌药物

• 批准号: 24658084
• 负责人: YAMAMOTO Kenji
• 金额: $ 2.58万
• 依托单位: Ishikawa Prefectural University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24658084/
• 关键词: スフィンゴ糖脂質; 抗生物質; 接合菌類; ガラクトース転移酵素; オーレオバシジンＡ; 糖鎖; セラミドガラクトシル転移酵素; 酵素; 菌類; 糖脂質; セラミド

We had found that Zygomycetes species showed resistance to Aureobasidin A, an antifungal agent. A novel family of neutral glycosphingolipids including galactosyl polymer was found in these fungi and the presence of biosynthetic pathway for the novel glycosphingolipids in Zygomycetes was elucidated. These results suggested that any inhibitor of this pathway may be effective for mucormycosis, which is a serious pathogenic disease for humans. We attempted to find any inhibitor of galactosyltransferase in these fungi. However, we failed to clone the galactosyltransferase genes of Rhizopus oryzae though we used animal cells or yeast as the host cells. Furthermore, we attempted to find any inhibitor of galactosyltransferase of Mucor hiemalis microsome but could not find it except alpha-methylglucoside having a weak inhibitory activity. We also tried to clone the gene of ceramide galactosyl transferase of Aspergillus oryzae. But we failed to clone it.

我们发现合子菌具有对抗真菌剂Aureobasidin A的抗性。在这些真菌中发现了一个新型的中性糖磷脂脂，包括半乳糖基聚合物，并阐明了新型糖磷脂的生物合成途径的存在。这些结果表明，该途径的任何抑制剂都可能有效，这对人类来说是一种严重的致病性疾病。 我们试图在这些真菌中找到任何半乳糖基转移酶的抑制剂。但是，尽管我们使用动物细胞或酵母作为宿主细胞，但我们未能克隆根茎的糖基转移酶基因。此外，我们试图找到任何粘液HIEMALIS微粒体的半乳糖基转移酶抑制剂，但除了具有弱抑制活性的α-甲基葡萄糖苷外找不到。我们还试图克隆曲霉曲霉的神经酰胺半乳糖基转移酶的基因。但是我们未能克隆它。