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1. (Article ID: 7027)
 
Bennion B, Park C, Fuller M, Lindsey R, Momany M, Jennemann R, Levery SB
Glycosphingolipids of the model fungus Aspergillus nidulans: characterization of GIPCs with oligo-alpha-mannose-type glycans
Journal of Lipid Research 44(11) (2003) 2073-2088
 

Aspergillus nidulans is a well-established nonpathogenic laboratory model for the opportunistic mycopathogen, A. fumigatus. Some recent studies have focused on possible functional roles of glycosphingolipids (GSLs) in these fungi. It has been demonstrated that biosynthesis of glycosylinositol phosphorylceramides (GIPCs) is required for normal cell cycle progression and polarized growth in A. nidulans (Cheng, J., T.-S. Park, A. S. Fischl, and X. S. Ye. 2001. Mol. Cell Biol. 21: 6198-6209); however, the structures of A. nidulans GIPCs were not addressed in that study, nor were the functional significance of individual structural variants and the downstream steps in their biosynthesis. To initiate such studies, acidic GSL components (designated An-2, -3, and -5) were isolated from A. nidulans and subjected to structural characterization by a combination of one-dimensional (1-D) and 2-D NMR spectroscopy, electrospray ionization-mass spectrometry (ESI-MS), ESI-MS/collision-induced decomposition-MS (MS/CID-MS), ESI-pseudo-[CID-MS](2), and gas chromatography-MS methods.jlr All three were determined to be GIPCs, with mannose as the only monosaccharide present in the headgroup glycans; An-2 and An-3 were identified as di- and trimannosyl inositol phosphorylceramides (IPCs) with the structures Manα1→3Manα1→2Ins1-P-1Cer and Manα1→3(Manα1→6)Manα1→2Ins1-P-1Cer, respectively (where Ins = myo-inositol, P = phosphodiester, and Cer = ceramide). An-5 was partially characterized, and is proposed to be a pentamannosyl IPC, based on the trimannosyl core structure of An-3.-Bennion, B., C. Park, M. Fuller, R. Lindsey, M. Momany, R. Jennemann, and S. B. Levery. Glycosphingolipids of the model fungus Aspergillus nidulans: characterization of GIPCs with oligo-α-mannose-type glycans.

NMR spectroscopy, mass spectrometry, glycolipid, tandem mass spectrometry, Electrospray Ionization, collision-induced dissociation, Aspergillus fumigatus

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2. (Article ID: 7243)
 
Levery SB, Momany M, Lindsey R, Toledo MS, Shayman JA, Fuller M, Brooks K, Doong RL, Straus AH, Takahashi HK
Disruption of the glucosylceramide biosynthetic pathway in Aspergillus nidulans and Aspergillus fumigatus by inhibitors of UDP-Glc:ceramide glucosyltransferase strongly affects spore germination, cell cycle, and hyphal growth
FEBS Letters 525(1-3) (2002) 59-64
 

The opportunistic mycopathogen Aspergillus fumigatus expresses both glucosylceramide and galactosylceramide (GlcCer and GalCer), but their functional significance in Aspergillus species is unknown. We here identified and characterized a GlcCer from Aspergillus nidulans, a non-pathogenic model fungus. Involvement of GlcCer in fungal development was tested on both species using a family of compounds known to inhibit GlcCer synthase in mammals. Two analogs, D-threo-1-phenyl-2-palmitoyl-3-pyrrolidinopropanol (P4) and D-threo-3',4'-ethylenedioxy-P4, strongly inhibited germination and hyphal growth. Neutral lipids from A. fumigatus cultured in the presence of these inhibitors displayed a significantly reduced GlcCer/GalCer ratio. These results suggest that synthesis of GlcCer is essential for normal development of A. fumigatus and A. nidulans.

glycosyltransferase, glycolipid, synthase, fungus, sphingolipid, PDMP

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