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

这项早期概念探索性研究（EAGER）奖通过生命过程化学项目和化学系化学催化项目获得，资助宾夕法尼亚大学的Eric Schelter博士研究第一个含稀土金属酶活性位点的功能模型复合物的电子结构，并合成新的高效醇脱氢催化剂。最近发现，在意大利索法拉火山口发现的一种有机体M. fumariolicum SoIV需要稀土金属才能生长。这一惊人的发现标志着人类首次发现生命所必需的稀土元素。最近还确定，这种生物体在一种关键酶中含有一个铈原子，这种酶用于将甲烷转化为生物体的食物来源。这个项目的重点是确定铈中心是如何做到这一点的，以及稀土元素在保持这些微生物存活方面的作用。这项工作将对我们对生命基本特征的理解产生广泛的影响，以及即使在极端恶劣的环境中，生命维持所需的条件。通过本项目培养的研究生将在生物无机化学和化学催化的界面上获得独特而多样的技能。该项目的研究结果将通过面向高中生和普通大众的推广项目进行传播。未被充分代表的群体，包括女研究生、一名非洲裔美国研究生、一名访问的非洲女科学家和一名拉丁裔博士后，将从该项目的支持中受益。最近的研究表明，甲基营养型富马霉对稀土金属La-Gd有必要的生长需求。测定了富马霉甲醇脱氢酶活性位点含有铈离子。这一惊人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。本应用的中心假设是Ce的金属氧化还原活性可以用来评估活性位点的电子结构，Ce-醌配合物在模型配合物中也会类似地诱导甲醇脱氢，RE离子的强刘易斯酸度使铈甲醇脱氢酶具有快速而独特的反应活性。该团队将通过模型复杂合成、电化学和密度泛函理论研究的结合来验证这一假设。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配合物。

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.