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

渴望更新：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

基本信息

批准号：
1608925
负责人：
Eric Schelter
金额：
$ 12万
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：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2018-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1608925&HistoricalAwards=false
关键词：
EAGER Renewal Bio Inorganic Chemistry

项目摘要

With this award the Chemistry of Life Processes (CLP) program in the Division of Chemistry (CHE) is funding Dr. Eric J. Schelter at the University of Pennsylvania for studies on one of only two known rare earth-containing enzymes. The rare earths are actually metals that are important to many of our modern electrical devices but are rarely, if ever, found in biological systems. The PI is studying an enzyme from a bacterium discovered in acidic volcanic mudpots, found to have rare earth elements as an essential growth requirement. This project is attempting to understand the unique characteristics and reactivity conferred to an enzyme isolated from these bacteria through the presence of cerium, one of the rare earth elements. The results are expanding understanding of new and unusual biochemistry, particularly as it concerns metabolism and energy. Students trained on this project are accruing skills in synthetic bioinorganic chemistry and chemical analysis. Undergraduate and graduate chemistry students from underrepresented groups are also benefiting from support of the project. A growing body of information suggests that rare earth elements play an important role in the global carbon cycle. Rare earth elements can incorporate the active site of a methanol dehydrogenase (MDH), encoded namely by the XoxF gene of M. fumariolicum SoIV, that includes a pyrroloquinoline quinone (PQQ) cofactor. The central hypothesis of this application is that quinolone quinones that replicate the electronic structure of PQQ, developed in the first stage of the project, will similarly induce alcohol dehydrogenation reactivity upon coordination with rare earth element cations in model complexes, and that the strong Lewis acidity of rare earth metal cations enable fast and unique reactivity for rare earth-XoxF-MDH. The overall goals of this proposal are to use a combination of synthesis, electrochemistry, Density Functional Theory (DFT) and high throughput experimentation to elucidate the unique physicochemical characteristics of the rare earth element-XoxF-MDH active site and to test functional model compounds of the active site in the catalytic dehydrogenation of small molecules.

凭借该奖项，化学部 (CHE) 的生命过程化学 (CLP) 项目正在资助宾夕法尼亚大学的 Eric J. Schelter 博士对仅有的两种已知的含稀土酶之一进行研究。稀土实际上是对我们许多现代电气设备很重要的金属，但在生物系统中却很少被发现。首席研究员正在研究一种在酸性火山泥盆中发现的细菌酶，该细菌含有稀土元素作为生长的基本要求。该项目试图了解通过稀土元素之一的铈的存在而从这些细菌中分离出来的酶所具有的独特特性和反应性。结果扩大了对新的和不寻常的生物化学的理解，特别是在新陈代谢和能量方面。接受该项目培训的学生正在积累合成生物无机化学和化学分析方面的技能。来自代表性不足群体的化学本科生和研究生也受益于该项目的支持。越来越多的信息表明稀土元素在全球碳循环中发挥着重要作用。稀土元素可以掺入甲醇脱氢酶 (MDH) 的活性位点，该酶由 M. fumariolicum SoIV 的 XoxF 基因编码，其中包括吡咯喹啉醌 (PQQ) 辅因子。该应用的中心假设是，在项目第一阶段开发的复制 PQQ 电子结构的喹诺酮醌，在与模型配合物中的稀土元素阳离子配位后，将类似地诱导醇脱氢反应性，并且强路易斯酸性稀土金属阳离子可实现稀土-XoxF-MDH 的快速且独特的反应性。该提案的总体目标是结合合成、电化学、密度泛函理论（DFT）和高通量实验来阐明稀土元素-XoxF-MDH活性位点的独特物理化学特性，并测试稀土元素的功能模型化合物小分子催化脱氢的活性位点。