混合键β(1,3)/β(1,4)-葡聚糖(MLG)通过摄入谷物在人类饮食中含量丰富,并广泛与代谢和胆固醇水平的健康影响有关。MLG也是人类肠道微生物群(HGM)的可发酵葡萄糖的主要来源。来自Prevotellaceae家族的细菌在食用植物丰富饮食的个体的HGM中具有很高的代表性,包括后工业社会中的某些土著人民和素食者。这里,我们已经定义并在功能上表征了典型的PrevotellaceaeMLG多糖利用基因座(MLG-PUL)。Prevotellacopri)DSM18205通过转录组学,生物化学,和结构生物学方法。特别是,S.copriMLG-PUL的细胞表面聚糖结合蛋白(SGBP)和糖苷水解酶(GH)的结构功能分析揭示了聚糖捕获和糖化的分子基础。值得注意的是,来自人类肠道的同势MLG-PULs,人类口腔,反刍动物肠道Prevotellaceae与拟杆菌科中的对应物的区别在于存在来自糖苷水解酶家族5,亚家族4(GH5_4)的β(1,3)特异性内切葡聚糖酶,该酶可引发MLG主链裂解。单个物种中同源MLG-PUL家族的定义使使用这些基因作为分子标记对近2000个人类粪便微生物组进行了调查。揭示了拟杆菌属和Prevotellaceae介导的MLG利用的全球种群特异性分布。总之,这里提供的数据为HGM中β-葡聚糖代谢的分子基础提供了新的见解,作为为改善人类和其他动物营养和健康的方法的发展提供信息的基础。
Mixed-linkage β(1,3)/β(1,4)-glucan (MLG) is abundant in the human diet through the ingestion of cereal grains, and is widely associated with healthful effects on metabolism and cholesterol levels. MLG is also a major source of fermentable glucose for the human gut microbiota (HGM). Bacteria from the Family Prevotellaceae are highly represented in the HGM of individuals who eat plant rich diets, including certain indigenous people and vegetarians in post-industrial societies. Here, we have defined and functionally characterized an exemplar Prevotellaceae MLG Polysaccharide Utilization Locus (MLG-PUL) in the type-strain Segatella copri (syn. Prevotella copri) DSM 18205 through transcriptomic, biochemical, and structural biological approaches. In particular, structure-function analysis of the cell-surface glycan-binding proteins (SGBP) and glycoside hydrolases (GH) of the S. copri MLG-PUL revealed the molecular basis for glycan capture and saccharification. Notably, syntenic MLG-PULs from human gut, human oral, and ruminant gut Prevotellaceae are distinguished from their counterparts in Bacteroidaceae by the presence of a β(1,3)-specific endo-glucanase from Glycoside Hydrolase Family 5, Subfamily 4 (GH5_4) that initiates MLG backbone cleavage. The definition of a family of homologous MLG-PULs in individual species enabled a survey of nearly 2000 human fecal microbiomes using these genes as molecular markers, which revealed global population-specific distributions of Bacteroidaceae- and Prevotellaceae-mediated MLG utilization. Altogether, the data presented here provide new insight into the molecular basis of β-glucan metabolism in the HGM, as a basis for informing the development of approaches to improve the nutrition and health of humans and other animals.