Besra G S, Sievert T, Lee R E, Slayden R A, Brennan P J, Takayama K
Department of Microbiology, Colorado State University, Fort Collins 80523.
Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12735-9. doi: 10.1073/pnas.91.26.12735.
The mycolic acids are large (C70-90) alpha-alkyl, beta-hydroxy fatty acids and are the major determinants of the mycobacterial cell wall's impermeable barrier. The biosynthesis of mycolic acids is barely understood (they are probably the products of specialized elongation and Claisen-type condensation), and yet their synthesis is the site of action of several mainline antituberculosis drugs. We describe the isolation from Mycobacterium smegmatis and the full characterization of a 6-O-mycolyl-beta-D-mannopyranosyl-1-monophosphoryl-3,7,11,15,19,23 ,27- heptamethyl-(2Z,6E,10E)-octacosatrien-1-ol . The identification of a mycolyl-mannosylphosphopolyprenol supported by cell-free labeling experiments and earlier literature suggests unusual biochemical pathways in which mature mycolic acids are formed from beta-oxo precursors while attached to a mannosyl-P-polyprenol, in which form they are transported through the membrane prior to final deposition as arabinan-bound mycolates.
分枝菌酸是大分子（C70 - 90）α-烷基、β-羟基脂肪酸，是分枝杆菌细胞壁不可渗透屏障的主要决定因素。分枝菌酸的生物合成几乎不为人所知（它们可能是特殊延伸和克莱森型缩合的产物），然而它们的合成是几种一线抗结核药物的作用位点。我们描述了从耻垢分枝杆菌中分离出一种6 - O - 分枝酰基 - β - D - 甘露吡喃糖基 - 1 - 单磷酸 - 3,7,11,15,19,23,27 - 七甲基 - (2Z,6E,10E) - 二十八碳三烯 - 1 - 醇，并对其进行了全面表征。无细胞标记实验和早期文献支持的分枝酰基 - 甘露糖基磷酸多萜醇的鉴定表明，存在不寻常的生化途径，即成熟的分枝菌酸由β-氧代前体在连接到甘露糖基 - P - 多萜醇时形成，它们以这种形式在最终作为阿拉伯聚糖结合的分枝菌酸盐沉积之前通过膜运输。
