Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Box 440, 405 30 Gothenburg, Sweden.
Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BX, U.K.
Essays Biochem. 2023 Apr 18;67(3):429-442. doi: 10.1042/EBC20220120.
Sulfated host glycans (mucin O-glycans and glycosaminoglycans [GAGs]) are critical nutrient sources and colonisation factors for Bacteroidetes of the human gut microbiota (HGM); a complex ecosystem comprising essential microorganisms that coevolved with humans to serve important roles in pathogen protection, immune signalling, and host nutrition. Carbohydrate sulfatases are essential enzymes to access sulfated host glycans and are capable of exquisite regio- and stereo-selective substrate recognition. In these enzymes, the common recognition features of each subfamily are correlated with their genomic and environmental context. The exo-acting carbohydrate sulfatases are attractive drug targets amenable to small-molecule screening and subsequent engineering, and their high specificity will help elucidate the role of glycan sulfation in health and disease. Inhibition of carbohydrate sulfatases provides potential routes to control Bacteroidetes growth and to explore the influence of host glycan metabolism by Bacteroidetes on the HGM ecosystem. The roles of carbohydrate sulfatases from the HGM organism Bacteroides thetaiotaomicron and the soil isolated Pedobacter heparinus (P. heparinus) in sulfated host glycan metabolism are examined and contrasted, and the structural features underpinning glycan recognition and specificity explored.
硫酸化宿主糖（粘蛋白 O-糖和糖胺聚糖 [GAG]）是人类肠道微生物群（HGM）中拟杆菌的关键营养来源和定植因素；HGM 是一个复杂的生态系统，由与人类共同进化的必需微生物组成，在病原体保护、免疫信号和宿主营养方面发挥着重要作用。碳水化合物硫酸酯酶是获取硫酸化宿主糖的必需酶，能够进行精细的区域和立体选择性的底物识别。在这些酶中，每个亚家族的常见识别特征与它们的基因组和环境背景相关。外切碳水化合物硫酸酯酶是有吸引力的药物靶点，可进行小分子筛选和后续工程改造，其高特异性将有助于阐明聚糖硫酸化在健康和疾病中的作用。碳水化合物硫酸酯酶的抑制为控制拟杆菌的生长以及探索拟杆菌对 HGM 生态系统中宿主糖代谢的影响提供了潜在途径。本文研究并对比了 HGM 生物拟杆菌（Bacteroides thetaiotaomicron）和土壤分离的肝素拟杆菌（Pedobacter heparinus）的碳水化合物硫酸酯酶在硫酸化宿主糖代谢中的作用，并探讨了糖识别和特异性的结构特征。
