Besra G S, Morehouse C B, Rittner C M, Waechter C J, Brennan P J
Department of Microbiology, Colorado State University, Fort Collins, Colorado 80523, USA.
J Biol Chem. 1997 Jul 18;272(29):18460-6. doi: 10.1074/jbc.272.29.18460.
The mycobacterial lipoglycans, lipomannan (LM) and lipoarabinomannan (LAM), are potent immunomodulators in tuberculosis and leprosy. Little is known of their biosynthesis, other than being based on phosphatidylinositol (PI), and they probably originate in the phosphatidylinositol mannosides (PIMs; PIMans). A novel form of cell-free incubation involving in vitro and in situ labeling with GDP-[14C]Man of the polyprenyl-P-mannoses (C35/C50-P-Man) and the simpler PIMs of mycobacterial membranes, reisolation of the [14C]Man-labeled membranes, and in situ chase demonstrated the synthesis of a novel alpha(1-->6)-linked linear form of LM at the expense of the C35/C50-P-Man. There was little or no synthesis under these conditions of PIMan5 with its terminal alpha(1-->2)Man unit or the mature LM or LAM with copious alpha(1-->2)Man branching. Synthesis of the linear LM, but not of the simpler PIMan2, was susceptible to amphomycin, a lipopeptide antibiotic that specifically inhibits polyprenyl-P-requiring translocases. A mixture of P[3H]I and P[3H]IMan2 was incorporated into the linear LM, supporting other evidence that, like the PIMs, LM and LAM, it is a lipid-linked mannooligosaccharide and a new member of the mycobacterial glycosylphosphatidylinositol lipoglycan/glycolipid class. Hence, the simpler PIMs originate in PI and GDP-Man, but further growth of the linear backbone emanates from C35-/C50-P-Man and is amphomycin-sensitive. The origin of the alpha(1-->2)Man branches of mature PIMan5, LM, and LAM is not known at this time but is probably GDP-Man.
分枝杆菌脂聚糖，即脂甘露聚糖（LM）和脂阿拉伯甘露聚糖（LAM），是结核病和麻风病中强大的免疫调节剂。除了基于磷脂酰肌醇（PI）之外，人们对它们的生物合成知之甚少，而且它们可能起源于磷脂酰肌醇甘露糖苷（PIMs；PIMans）。一种新型的无细胞培养形式，包括用GDP-[14C]甘露糖对多萜醇-P-甘露糖（C35/C50-P-Man）和分枝杆菌膜中较简单的PIMs进行体外和原位标记，重新分离[14C]甘露糖标记的膜，并进行原位追踪，结果表明以C35/C50-P-Man为代价合成了一种新型的α(1→6)连接的线性LM。在这些条件下，几乎没有合成带有末端α(1→2)甘露糖单元的PIMan5，也没有合成带有大量α(1→2)甘露糖分支的成熟LM或LAM。线性LM的合成，但不是较简单的PIMan2的合成，对两性霉素敏感，两性霉素是一种脂肽抗生素，可特异性抑制需要多萜醇-P的转位酶。P[3H]I和P[3H]IMan2的混合物被掺入线性LM中，这支持了其他证据，即与PIMs、LM和LAM一样，它是一种脂质连接的甘露寡糖，是分枝杆菌糖基磷脂酰肌醇脂聚糖/糖脂类的新成员。因此，较简单的PIMs起源于PI和GDP-甘露糖，但线性主链的进一步生长源自C35-/C50-P-Man，并且对两性霉素敏感。成熟的PIMan5、LM和LAM的α(1→2)甘露糖分支的起源目前尚不清楚，但可能是GDP-甘露糖。
