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

通过这一奖项，化学部(CHE)生命过程化学(CLP)项目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中的一种进行研究。稀土实际上是对我们许多现代电子设备很重要的金属，但在生物系统中很少发现。PI正在研究一种来自酸性火山泥盆中发现的细菌的酶，这种细菌被发现含有稀土元素作为必要的生长条件。这个项目试图了解从这些细菌中分离出来的一种酶的独特特性和反应活性，这种酶是通过稀土元素之一铈的存在而产生的。这些结果正在扩大对新的和不寻常的生物化学的理解，特别是在涉及新陈代谢和能量的时候。在这个项目上接受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扮演着重要角色。稀土元素可以结合甲醇脱氢酶(MDH)的活性部位，即由烟曲霉菌SoIV的XoxF基因编码，该基因包括一个吡咯喹啉醌(PQQ)辅因子。这一应用的中心假设是，在项目第一阶段开发的复制PQQ电子结构的喹诺酮类化合物，在与模型络合物中的稀土元素阳离子配位时，将类似地诱导醇脱氢反应，并且稀土金属阳离子的强Lewis酸性使稀土-XoxF-MDH具有快速而独特的反应活性。该方案的总体目标是利用合成、电化学、密度泛函理论(DFT)和高通量实验相结合的方法，阐明稀土元素XoxF-MDH活性中心独特的物理化学特征，并测试活性中心在小分子催化脱氢中的功能模型化合物。

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.