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

我们发现接合菌对Aureobasidin A有抗药性。在这些真菌中发现了一个新的中性鞘糖脂家族，包括半乳糖基聚合物，并阐明了接合菌中新鞘糖脂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对毛霉菌病有效，毛霉菌病是人类的一种严重致病性疾病。 我们试图在这些真菌中找到半乳糖基转移酶的抑制剂。然而，我们用动物细胞或酵母作为宿主细胞，都未能克隆到根霉的半乳糖基转移酶基因。此外，我们试图找到任何半乳糖基转移酶的抑制剂的Mucor hiemalis微粒体，但没有发现它除了α-甲基葡萄糖苷具有弱的抑制活性。我们还试图克隆曲霉神经酰胺半乳糖基转移酶基因。但我们克隆失败了。

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.