Novel Biochemical Pathways for the Metabolism of Carbohydrates in the Human gut Micriobiome

这项研究计划的主要焦点将是识别、发现和 阐明复杂碳水化合物在人体内代谢的新生化途径 肠道微生物群。目前，已鉴定出一千多种不同的细菌种类 人类肠道和这些细菌中包含的基因总数超过了 人类基因的数量增加了两个数量级以上。此外，它已经被证明是 人类肠道微生物群的组成和相关的代谢多样性包含 这些细菌对维持人类健康和生理有很大贡献。 不幸的是，相当一部分的酶和相应的代谢途径包含 在人类肠道中发现的细菌中有一种不确定的、未知的或不正确的功能 注释。这种不确定性表明，新陈代谢潜力的很大一部分包含在 在人类肠道内，微生物群仍有待于适当的描述。我们计划进行的实验 发现和阐明新陈代谢途径的途径 复合碳水化合物将涉及生物信息学的协调和协同利用， 计算生物学、蛋白质三维结构测定、代谢组学和 重点化合物文库的物理筛选。底物和反应的测定 新发现的酶催化反应中包含的多样性将提供独特的 对新型酶进化和发展的分子机制的洞察 并将为治疗干预提供潜在的目标。

The primary focus of this research proposal will be the identification, discovery, and elucidation of novel biochemical pathways for the metabolism of complex carbohydrates in the human gut microbiome. Currently, more than one thousand different bacterial species have been identified in the human intestinal tract and the total number of genes contained within these bacteria exceeds the number of human genes by more than two orders of magnitude. Moreover, it has been demonstrated that the composition of the human gut microbiome and the associated metabolic diversity contained within these bacteria contribute significantly to the maintenance of human health and physiology. Unfortunately, a significant fraction of the enzymes and corresponding metabolic pathways contained within the bacteria found in the human gut have an uncertain, unknown, or incorrect functional annotation. This uncertainty suggests that a substantial fraction of the metabolic potential contained within the human gut microbiome remains to be properly characterized. Our proposed experimental approach for the discovery and elucidation of novel metabolic pathways for the metabolism of complex carbohydrates will involve the concerted and synergistic utilization of bioinformatics, computational biology, three-dimensional protein structure determination, metabolomics and physical screening of focused compound libraries. The determination of the substrate and reaction diversity contained within the newly discovered enzyme-catalyzed reactions will provide unique insights into the molecular mechanisms for the evolution and development of novel enzymatic activities and will provide potential targets for therapeutic intervention.