Manchester Institute of Biotechnology, University of Manchester, 131 Princess Street, Manchester, U.K.
Division of Molecular Microbiology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
Biochem J. 2021 Feb 26;478(4):685-701. doi: 10.1042/BCJ20200505.
Rhamnose is an important 6-deoxy sugar present in many natural products, glycoproteins, and structural polysaccharides. Whilst predominantly found as the l-enantiomer, instances of d-rhamnose are also found in nature, particularly in the Pseudomonads bacteria. Interestingly, rhamnose is notably absent from humans and other animals, which poses unique opportunities for drug discovery targeted towards rhamnose utilizing enzymes from pathogenic bacteria. Whilst the biosynthesis of nucleotide-activated rhamnose (NDP-rhamnose) is well studied, the study of rhamnosyltransferases that synthesize rhamnose-containing glycoconjugates is the current focus amongst the scientific community. In this review, we describe where rhamnose has been found in nature, as well as what is known about TDP-β-l-rhamnose, UDP-β-l-rhamnose, and GDP-α-d-rhamnose biosynthesis. We then focus on examples of rhamnosyltransferases that have been characterized using both in vivo and in vitro approaches from plants and bacteria, highlighting enzymes where 3D structures have been obtained. The ongoing study of rhamnose and rhamnosyltransferases, in particular in pathogenic organisms, is important to inform future drug discovery projects and vaccine development.
鼠李糖是一种存在于许多天然产物、糖蛋白和结构多糖中的重要 6-去氧糖。虽然主要以 l-对映异构体形式存在，但 d-鼠李糖在自然界中也有发现，特别是在假单胞菌细菌中。有趣的是，鼠李糖在人和其他动物中明显不存在，这为针对利用致病性细菌中的酶的鼠李糖利用酶的药物发现提供了独特的机会。虽然核苷酸激活的鼠李糖（NDP-鼠李糖）的生物合成已有很好的研究，但合成含鼠李糖糖缀合物的鼠李糖基转移酶的研究是当前科学界的重点。在这篇综述中，我们描述了鼠李糖在自然界中的存在位置，以及 TDP-β-l-鼠李糖、UDP-β-l-鼠李糖和 GDP-α-d-鼠李糖生物合成的已知情况。然后，我们重点介绍了使用植物和细菌中的体内和体外方法进行表征的鼠李糖基转移酶的例子，强调了获得三维结构的酶。对鼠李糖和鼠李糖基转移酶的持续研究，特别是在致病生物体中，对于为未来的药物发现项目和疫苗开发提供信息非常重要。
