Microbial Dark Matter: Forging New Discoveries in Metabolism

微生物暗物质：新陈代谢的新发现

基本信息

批准号：
1714556
负责人：
Valerie Copie
金额：
$ 53.5万
依托单位：
Montana State University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2022-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1714556&HistoricalAwards=false
关键词：
Microbial Dark Matter Forging New

项目摘要

What factors allow single-celled microbial organisms to not only survive, but actively seek out environments that humans consider highly toxic? Scientists have learned much about how these tiny living creatures function, facilitating breakthroughs in medical, energy, and bioremediation sciences. However, the understanding of how microorganisms grow and thrive in harsh environments remains largely cloaked in mystery. The ability to predict how microorganisms will respond to environmental changes or the knowledge of the types of reactions that occur inside and outside their cells is vastly under-represented. In a large part, this is due to the limited ability to identify the small molecules produced and consumed by microbes (metabolites). This unknown microbial metabolite landscape limits the understanding of the microbial processes playing key roles in the regulation of biogeochemical cycles, bioremediation, bioenergy production, as well as the human microbiome. In this work, state of the art techniques will be used to find and characterize metabolites that up until now have been largely invisible to researchers. The work will result in excellent training opportunities for undergraduate and graduate students, especially from under-represented groups such as Native Americans, as well as a series of lectures at the Thermal Biology Institute that provide an opportunity for effective outreach and give the public a view of the importance of microbes. This project focuses on the discovery of unknown microbial metabolites produced by bacteria using the Gram-negative soil bacterium Agrobacterium tumefaciens strain 5A as model. This bacterium is a model for understanding how microbes metabolize arsenic, a critical environmental toxin found in contaminated soils and water supplies, and a top priority for bioremediation efforts. Focusing on how microbes metabolize arsenic is important because microorganisms influence arsenic toxicity and bioavailability in every environment thus far studied. Thus, characterization of arsenicals produced by microbes are a focal point of this project that will employ state-of-the-art nuclear magnetic resonance (NMR) and mass spectrometry (MS) metabolomics technology to identify unknown microbial compounds, including arsenicals (i.e. methylated species, arsenolipids, arsenosugars). Importantly, the analytical approaches developed in this project will be applicable to many facets of biology. The project will greatly enhance researchers' abilities to probe the richness of the metabolomes of microbes, and to gain a much better appreciation for the diversity of microbial unknown small molecules. Focusing on A. tumefaciens as a model system will enable the identification and structural characterization of novel organo-arsenic compounds and arsenolipids. Results from these studies will bring transformative knowledge to the field of microbe-arsenic interactions relevant to scientific research aimed at predicting how arsenic disrupts/alters bacterial metabolism in situ, with broader implications for biogeochemical carbon and nitrogen cycling in nature when microbes must deal with arsenic.

哪些因素允许单细胞微生物不仅生存，还可以积极寻找人类认为剧毒的环境？科学家已经了解了这些微小的生物如何发挥作用，促进医学，能源和生物修复科学的突破。然而，对微生物在恶劣环境中如何成长和繁荣的理解仍然在很大程度上被神秘。预测微生物将如何应对环境变化的能力或对其细胞内部和外部发生的反应类型的了解的能力大大不足。在很大程度上，这是由于鉴定微生物（代谢物）产生和消耗的小分子的能力有限。这个未知的微生物代谢产物景观限制了对微生物过程在调节生物地球化学周期，生物修复，生物能源产生以及人类微生物组中起关键作用的理解。在这项工作中，最先进的技术将用于查找和表征迄今为止研究人员在很大程度上看不见的代谢产物。这项工作将为本科生和研究生提供极好的培训机会，尤其是来自代表性不足的团体，例如美洲原住民，以及在热生物学研究所的一系列讲座，为有效的外展活动提供了机会，并使公众对微生物的重要性有所了解。该项目的重点是使用革兰氏阴性土壤细菌Tumefaciens菌株5a作为模型发现细菌产生的未知微生物代谢产物。该细菌是一种模型，用于了解微生物如何代谢砷，这是在受污染的土壤和水供应中发现的关键环境毒素，以及生物修复工作的首要任务。关注微生物如何代谢砷很重要，因为微生物在迄今为止所研究的每个环境下都会影响砷的毒性和生物利用度。因此，由微生物生产的砷的表征是该项目的焦点，该项目将采用最先进的核磁共振（NMR）和质谱法（MS）代谢组学技术来识别未知的微生物化合物，包括砷，即甲基化的物种，甲基化的物种，Arsenolipids，Arsenosugars）。重要的是，该项目中开发的分析方法将适用于生物学的许多方面。该项目将大大提高研究人员的能力，以探测微生物代谢的丰富性，并对微生物未知小分子的多样性获得更好的欣赏。专注于A. tumefaciens作为模型系统将使新型有机疗法化合物和砷脂的鉴定和结构表征能够识别和结构表征。这些研究的结果将为与科学研究相关的微生物 - 砷相互作用的领域带来变革性知识，旨在预测砷的破坏/改变现场的细菌代谢，对生物地球化学碳和氮气自然循环的生物地球化学碳和硝基循环的含义更广泛。