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.

项目摘要/摘要 NIH人类微生物组项目（HMP）彻底改变了我们对人类的看法 微生物相互作用，并为研究提供了巨大的动力，以获得很多 更深入地了解微生物如何影响人类健康。 HMP的肠道微生物 参考基因组和人类胃肠道培养物含有961 代表142属的物种。然而，对这些微生物的了解相对较少。 在这里，我们将检验以下假设：钨（W），一种金属几乎从未考虑过生物学 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 揭示了许多这些肠道微生物包含编码各种成员的基因 含W的氧化还原酶（WOR）酶家族。只有极少数的酶有 以前是表征，主要来自外来的嗜热微生物。总体目标 拟议的研究表明，Wor家族的其他成员在 肠道微生物组。在初步研究中，我们表明一些肠道微生物占据痕迹 W及其含W的量消除了反应性和潜在有毒的醛 在肠道中发现，是由煮熟的食物和微生物组代谢产生的。其他W- 提出含有危害的危机来催化其他反应。在提议中 研究我们将通过W-Monitored（使用ICP-MS）纯化十种新型系统发育明显的恶化（使用ICP-MS） 厌氧色谱。它们的催化活性和生理底物将是 通过酶诱导的代谢组学方法（使用LC-MS）确定。另外，我们 提出其中一些恶化是电子分叉的酶 Exermonic和Endervonic反应，最近发现的能源保护机制 生物系统。动力学，光谱（使用EPR）和结构（使用冷冻）分析 W-酶的该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，各种恶化的生理功能将 确定，我们将确定W对肠道微生物的代谢的影响， 包括它们抵抗肠道和烹饪相关的醛。