Joo Joanna, Koid Andrea, Kim Hanee, Ghosh Antara, Lee Seayoung, Sheshova Mia, Lupoli Tania J
Department of Chemistry, New York University, New York, New York 10003, United States.
Biochemistry. 2025 Sep 2;64(17):3663-3680. doi: 10.1021/acs.biochem.5c00338. Epub 2025 Aug 20.
While humans utilize approximately ten building blocks, hundreds of "rare" sugars exist, which are absent in mammals but present in microbes, plants, and other natural sources. In addition to the common sugars found across organisms, more than 700 different rare monosaccharides exist, many of which are prokaryote-specific and utilized across bacteria to decorate natural products and various other glycoconjugates. As the outer glycocalyx layer of bacterial cells is composed of glycolipids, glycoproteins, and polysaccharides, rare sugars are enriched on the cell surface and are major components of structures known to mediate interactions with other cells and the environment. Despite their importance in biology, there remain many open questions in the field of biochemistry regarding the biosynthesis and functions of rare sugars. This perspective highlights ongoing biochemical work on prokaryotic rare sugars, including approaches to study the incorporation of rare sugars into cellular glycans, to develop chemical and enzymatic routes for generating rare sugar probes and glycans, and to analyze rare sugar-protein interactions. Opportunities to improve the sequencing efforts of microbial glycans through experimental and computational approaches are also discussed, along with potential therapeutic applications of rare sugar-containing molecules. In covering these topics, we emphasize tools that have not yet been utilized to study rare sugars but may be used for future approaches that will expand our knowledge of their distinct roles in microbes and the interplay between pathogens and their hosts.
人类大约利用十种构建模块，而存在数百种“稀有”糖，它们在哺乳动物中不存在，但存在于微生物、植物和其他天然来源中。除了在各种生物体中发现的常见糖类外，还存在700多种不同的稀有单糖，其中许多是原核生物特有的，在细菌中用于修饰天然产物和各种其他糖缀合物。由于细菌细胞的外层糖萼层由糖脂、糖蛋白和多糖组成，稀有糖在细胞表面富集，是已知介导与其他细胞和环境相互作用的结构的主要成分。尽管稀有糖在生物学中很重要，但在生物化学领域，关于稀有糖的生物合成和功能仍有许多悬而未决的问题。本文观点强调了目前关于原核生物稀有糖的生物化学研究工作，包括研究稀有糖掺入细胞聚糖的方法、开发生成稀有糖探针和聚糖的化学和酶促途径，以及分析稀有糖与蛋白质的相互作用。还讨论了通过实验和计算方法改进微生物聚糖测序工作的机会，以及含稀有糖分子的潜在治疗应用。在涵盖这些主题时，我们强调了尚未用于研究稀有糖但可用于未来方法的工具，这些方法将扩展我们对它们在微生物中的独特作用以及病原体与其宿主之间相互作用的认识。
