Zhang Yi, Fechter Eric J, Wang Tsung-Shing Andrew, Barrett Dianah, Walker Suzanne, Kahne Daniel E
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
J Am Chem Soc. 2007 Mar 21;129(11):3080-1. doi: 10.1021/ja069060g. Epub 2007 Feb 27.
Bacteria are surrounded by a cell wall containing layers of peptidoglycan, the integrity of which is essential for bacterial survival. In the final stage of peptidoglycan biosynthesis, peptidoglycan glycosyltransferases (PGTs; also known as transglycosylases) catalyze the polymerization of Lipid II to form linear glycan chains. PGTs have tremendous potential as antibiotic targets, but the potential has not yet been realized. Mechanistic studies have been hampered by a lack of substrates to monitor enzymatic activity. We report here the total synthesis of heptaprenyl-Lipid IV and its use to study two different PGTs from . We show that one PGT can couple Lipid IV to itself whereas the other can only couple Lipid IV to Lipid II. These differences in enzymatic activity may reflect differences in the biological functions of the two major glycosyltransferases in .
细菌被含有肽聚糖层的细胞壁所包围，肽聚糖的完整性对于细菌的生存至关重要。在肽聚糖生物合成的最后阶段，肽聚糖糖基转移酶（PGTs；也称为转糖基酶）催化脂质II聚合形成线性聚糖链。PGTs作为抗生素靶点具有巨大潜力，但这一潜力尚未实现。由于缺乏监测酶活性的底物，机理研究受到了阻碍。我们在此报告了庚二烯基 - 脂质IV的全合成及其用于研究来自[具体来源未给出]的两种不同PGTs的情况。我们表明，一种PGT可以将脂质IV自身偶联，而另一种只能将脂质IV与脂质II偶联。这些酶活性的差异可能反映了[具体来源未给出]中两种主要糖基转移酶生物学功能的差异。
