期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2006
卷号：103
期号：25
页码：9458-9463
DOI：10.1073/pnas.0603539103
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Infective stages of the protozoan parasite Leishmania spp. accumulate a class of [beta]-1,2-mannan oligosaccharides as their major carbohydrate reserve material. Here, we describe the biosynthesis of Leishmania mannan. Mannan precursors were identified by metabolic labeling of Leishmania mexicana promastigotes with [3H]mannose. Label was initially incorporated into a phosphomannose primer and short phosphorylated [beta]-1,2-mannan oligomers that were two to five residues long. Analysis of the mannan primer by Fourier transform ion-cyclotron resonance MS and various enzymatic and chemical treatments and comparison with authentic mannose (Man) phosphates indicated the presence of Man-{alpha}-1,4-cyclic phosphate. This primer was synthesized from Man-6-phosphate by means of Man-1-phosphate in a cell-free system. Short mannan chains containing the primer were subsequently dephosphorylated and then further elongated by GDP-Man-dependent transferases in vivo and in the cell-free system. The synthesis of this glycan primer likely constitutes a key regulatory step in mannan biosynthesis and is a potential target for antileishmanial drugs.
