Newly discovered neutral glycosphingolipids in aureobasidin A-resistant zygomycetes: Identification of a novel family of Gala-series glycolipids with core Gal alpha 1-6Gal beta 1-6Gal beta sequences

• Published in: The Journal of biological chemistry 2004-07, Vol.279 (31), p.32028-32034
• Main Authors: Aoki, Kazuhiro, Uchiyama, Ryosuke, Yamauchi, Suguru, Katayama, Takane, Itonori, Saki, Sugita, Mutsumi, Hada, Noriyasu, Yamada-Hada, Junko, Takeda, Tadahiro, Kumagai, Hidehiko, Yamamoto, Kenji
• Format: Article
• Language: English
• Subjects: Absidia - metabolism; Antifungal Agents - pharmacology; Aspergillus - metabolism; Carbohydrates - chemistry; Chromatography, Thin Layer; Depsipeptides; Drug Resistance; Gas Chromatography-Mass Spectrometry; Glycolipids - chemistry; Glycoside Hydrolases - metabolism; Glycosphingolipids - chemistry; Magnetic Resonance Spectroscopy; Models, Chemical; Mucor - metabolism; Mucormycosis; Multigene Family; Penicillium - metabolism; Peptides, Cyclic - pharmacology; Rhizopus - metabolism; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Sphingolipids - metabolism; Sphingosine - analogs & derivatives; Sphingosine - chemistry
• ISSN: 0021-9258
• DOI: 10.1074/jbc.M312918200

We found for the first time that Zygomycetes species showed resistance to Aureobasidin A, an antifungal agent. A novel family of neutral glycosphingolipids (GSLs) was found in these fungi and isolated from Mucor hiemalis, which is a typical Zygomycetes species. Their structures were completely determined by compositional sugar, fatty acid, and sphingoid analyses, methylation analysis, matrix-assisted laser desorption ionization time-of-flight/mass spectrometry, and (1)H NMR spectroscopy. They were as follows: Gal beta 1-6Gal beta 1-1Cer (CDS), Gal alpha 1-6Gal beta 1-6Gal beta 1-1Cer (CTS), Gal alpha 1-6Gal alpha 1-6Gal beta 1-6Gal beta 1-1Cer (CTeS), and Gal alpha 1-6Gal alpha 1-6Gal alpha 1-6Gal beta 1-6Gal beta 1-1Cer (CPS). The ceramide moieties of these GSLs consist of 24:0, 25:0, and 26:0 2-hydroxy acids as major fatty acids and 4-hydroxyoctadecasphinganine (phytosphingosine) as the sole sphingoid. However, the glycosylinositolphosphoceramide families that are the major GSLs components in fungi were not detected in Zygomycetes at all. This seems to be the reason that Aureobasidin A is not effective for Zygomycetes as an antifungal agent. Our results indicate that the biosynthetic pathway for GSLs in Zygomycetes is significantly different from those in other fungi and suggest that any inhibitor of this pathway may be effective for mucormycosis, which is a serious pathogenic disease for humans.