W-Health: Tungsten is an Essential Metal for a Healthy Gut Microbiome

W-Health：钨是健康肠道微生物组的必需金属

• 批准号: 10386032
• 负责人: Michael W. Adams
• 金额: $ 17.54万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-20 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10386032
• 关键词: Aldehydes; Anaerobic Bacteria; Bioinformatics; Chromatography; Collection; Cryoelectron Microscopy; Electrons; Enzymes; Family; Food; Genes; Genome; Goals; Health; Human; Human Microbiome; Inductively Coupled Plasma Mass Spectrometry; Kinetics; Metabolic; Metabolism; Metals; Microbe; Monitor; Nature; Oxidoreductase; Phylogenetic Analysis; Physiological; Reaction; Research; Resistance; Structure; Testing; Tungsten; United States National Institutes of Health; base; biological systems; cooking; gastrointestinal bacteria; gut microbes; gut microbiome; member; metabolomics; microbiome; microorganism; novel; reconstruction; reference genome

Project Summary/Abstract The NIH Human Microbiome Project (HMP) revolutionized our perspective on human- microbe interactions and provided a tremendous impetus for research in order to obtain a much deeper understanding of how microbes impact human health. The gut microorganisms of the HMP Reference Genomes and the Human Gastrointestinal Bacteria Culture Collection contain 961 species representing 142 genera. Yet, relatively little is known about these microorganisms. Herein we will test the hypothesis that tungsten (W), a metal almost never considered in biological systems, is essential for the health of the human gut microbiome. Our bioinformatics analyses reveal that a large number of these gut microbes contain genes encoding diverse members of the W-containing oxidoreductase (WOR) family of enzymes. Only a very few WOR enzymes have been previously characterized, mainly from exotic thermophilic microbes. The overall goal of the proposed research is to show that other members of the WOR family have essential functions in the gut microbiome. In preliminary studies, we have shown that some gut microbes take up trace amounts of W and their W-containing WORs remove reactive and potentially toxic aldehydes found in the gut, which are generated from cooked foods and microbiome metabolism. Other W- containing WORs are proposed to catalyze other as yet unknown reactions. In the proposed research we will purify ten novel phylogenetically distinct WORs by W-monitored (using ICP-MS) anaerobic chromatography. Their catalytic activities and physiological substrates will be determined by an enzyme-induced metabolomics approach (using LC-MS). In addition, we propose that some of these WORs are electron bifurcating enzymes that simultaneously couple exergonic and endergonic reactions, a recently discovered mechanism of energy conservation in biological systems. Kinetic, spectroscopic (using EPR) and structural (using cryoEM) analyses of this subset of W-enzymes will be used to investigate the nature of the bifurcation reactions. Using genome-based metabolic reconstructions, the physiological functions of the various WORs will be ascertained and we will determine the effects of W on the metabolism of the gut microbes, including on their resistance to gut- and cooking-related aldehydes.

项目概要/摘要 NIH 人类微生物组计划 (HMP) 彻底改变了我们对人类微生物组的看法 微生物相互作用并为研究提供了巨大的推动力，以获得更多的信息 更深入地了解微生物如何影响人类健康。 HMP 的肠道微生物 961 参考基因组和人类胃肠道细菌培养物保藏中心 代表142属的物种。然而，人们对这些微生物知之甚少。 在此，我们将检验以下假设：钨 (W)，一种在生物中几乎从未考虑过的金属 系统，对于人类肠道微生物组的健康至关重要。我们的生物信息学分析 研究表明，大量肠道微生物含有编码不同成员的基因 含 W 的氧化还原酶 (WOR) 家族酶。只有极少数 WOR 酶具有 之前已对其进行了表征，主要来自外来嗜热微生物。该项目的总体目标是 拟议的研究旨在表明 WOR 家族的其他成员在 肠道微生物群。在初步研究中，我们已经表明一些肠道微生物吸收微量 一定量的钨及其含钨 WOR 可去除活性醛和潜在有毒的醛 存在于肠道中，由熟食和微生物代谢产生。其他 W- 含有 WOR 的材料被认为可以催化其他未知的反应。在提议的 研究中，我们将通过 W 监测（使用 ICP-MS）纯化十个新的系统发育不同的 WOR 厌氧色谱法。它们的催化活性和生理底物将是 通过酶诱导代谢组学方法（使用 LC-MS）测定。此外，我们 提出其中一些 WOR 是同时耦合的电子分叉酶 放能和吸能反应是最近发现的能量守恒机制 生物系统。动力学、光谱（使用 EPR）和结构（使用冷冻电镜）分析 W 酶的这个子集将用于研究分叉反应的性质。使用 基于基因组的代谢重建，各种WOR的生理功能将 得到确定，我们将确定 W 对肠道微生物代谢的影响， 包括它们对肠道和烹饪相关醛类的抵抗力。