EAGER: Bio-Inorganic Chemistry of the Rare Earth Metals: Chemistry Relevant to the Cerium-Dependent Methanol Dehydrogenase

EAGER：稀土金属的生物无机化学：与铈依赖性甲醇脱氢酶相关的化学

• 批准号: 1449246
• 负责人: Eric Schelter
• 金额: $ 21.56万
• 依托单位: University of Pennsylvania
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-15 至 2016-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1449246&HistoricalAwards=false
• 关键词: EAGER; Bio; Inorganic; Chemistry; Rare

This EArly-concept Grant for Exploratory Research (EAGER) award through the Chemistry of Life Processes Program and Chemical Catalysis Program in the Division of Chemistry is funding Dr. Eric Schelter of the University of Pennsylvania to study the electronic structure of functional model complexes of the active site of the first rare earth-containing metalloenzyme and to synthesize new efficient catalysts for the dehydrogenation of alcohols. It has been recently discovered that M. fumariolicum SoIV, an organism found in the Sofatara Crater in Italy, requires rare earth metals in order to grow. This surprising finding marks the first time that any rare earth elements have been found to be necessary for life. It has also been recently determined that the organism possesses a cerium atom in a key enzyme used to convert methane into a food source for the organism. This project is focused on determining exactly how the cerium center does this and what the role of the rare earth elements are in keeping these microbes alive. This work will have a broad impact on our understanding of the basic features of life and what is required for life to be sustained, even in extremely harsh environments. Graduate students trained through this project will acquire unique and diverse skills at the interface of bioinorganic chemistry and chemical catalysis. The findings of the project will be communicated through outreach programs targeted toward high school students and the general public. Underrepresented groups including women graduate students, an African American graduate student, a visiting African woman scientist and a Latino postdoctoral associate will benefit from support of the project. Recent studies have shown that the methylotrophic M. fumariolicum SolV has an essential growth requirement for the rare earth metals La-Gd. The methanol dehydrogenase enzyme of M. fumariolicum SolV was determined to have a cerium cation in its active site. This surprising finding marked the first instance that rare earth elements (RE = La-Gd, Sc and Lu) were shown to have an essential biochemical role. The central hypothesis of this application is that the metal redox activity of Ce can be used to evaluate the electronic structure of the active site, that Ce-quinone complexes will similarly induce methanol dehydrogenation in model complexes, and that the strong Lewis acidity of RE cations enable fast and unique reactivity for the cerium methanol dehydrogenase. The team will test the hypothesis through a combination of model complex synthesis, electrochemistry and density functional theory studies. The overall goals of the research are to determine the electronic structure of the cerium active site and to synthesize functional model complexes of the enzyme that catalyze the dehydrogenation of alcohols.

这项早期概念探索性研究资助 (EAGER) 奖项通过化学系生命过程化学项目和化学催化项目资助，资助宾夕法尼亚大学的埃里克·谢尔特 (Eric Sc​​helter) 博士研究功能模型复合物的电子结构。第一个含稀土金属酶的活性位点，并合成用于醇脱氢的新型高效催化剂。最近发现，在意大利索法塔拉火山口发现的一种微生物 M. fumariolicum SoIV 需要稀土金属才能生长。这一令人惊讶的发现标志着首次发现稀土元素是生命所必需的。最近还确定该生物体在一种关键酶中拥有一个铈原子，该酶用于将甲烷转化为该生物体的食物来源。该项目的重点是确定铈中心如何做到这一点，以及稀土元素在保持这些微生物存活方面的作用。这项工作将对我们理解生命的基本特征以及即使在极其恶劣的环境下维持生命所需的条件产生广泛的影响。 通过该项目培训的研究生将获得生物无机化学和化学催化领域独特且多样化的技能。该项目的研究结果将通过针对高中生和公众的外展计划进行传达。代表性不足的群体，包括女研究生、非裔美国研究生、访问非洲女科学家和拉丁裔博士后助理，将受益于该项目的支持。最近的研究表明，甲基营养型 M. fumariolicum SolV 对稀土金属 La-Gd 具有重要的生长需求。经测定，M. fumariolicum SolV 的甲醇脱氢酶在其活性位点具有铈阳离子。这一令人惊讶的发现标志着稀土元素（RE = La-Gd、Sc 和 Lu）首次被证明具有重要的生化作用。该应用的中心假设是，Ce的金属氧化还原活性可用于评估活性位点的电子结构，Ce-醌配合物将类似地诱导模型配合物中的甲醇脱氢，并且RE阳离子的强路易斯酸性使铈甲醇脱氢酶具有快速且独特的反应性。该团队将通过模型复合物合成、电化学和密度泛函理论研究的结合来检验这一假设。该研究的总体目标是确定铈活性位点的电子结构并合成催化醇脱氢的酶的功能模型复合物。