Spectroscopic and Mechanistic Studies of Rare Earth Element Dependent Enzymes

镧系元素（Ln）是元素周期表中由镧到镥的元素，在自然界中含量丰富，但由于其溶解度低，生物利用度差。然而，许多细菌在生化过程中使用这些元素。更具体地说，细菌利用镧和钕等三价镧作为甲醇脱氢酶（MDH）酶活性位点的辅助因子，该酶催化甲醇氧化为甲醛，作为其一碳（C1）能量代谢的一部分。以前，人们认为含钙MDH （Ca-MDH）是细菌氧化甲醇的主要途径。该项目的主要目的是了解为什么大自然选择镧系元素来催化许多细菌必需的甲醇氧化。这种理解将来自于研究甲醇脱氢酶的机理方面，以及在不同pH值、温度、不同镧系元素（和钙）下的动力学参数的仔细比较，以及比较光谱特征。具体来说，我们想要回答以下问题：为什么一些细菌从Ca-MDH转变为Ln- mdh，即使只有纳摩尔浓度的Ln？ln - mdh比Ca-MDH好吗？酒精氧化的机制是什么？为什么某些镧系元素（较大的，早期的Ln）比其他镧系元素（较晚的，较小的Ln）更有效地转化甲醇？

Lanthanides (Ln), the elements lanthanum to lutetium in the periodic table, are abundant in nature but due to their low solubility poorly bioavailable. Nevertheless, many bacteria use these elements in biochemical processes. More specifically, bacteria utilize the trivalent Ln such as lanthanum and neodymium as cofactors in the active sites of methanol dehydrogenase (MDH) enzymes, which catalyse the oxidation of methanol to formaldehyde as part of their one-carbon (C1) energy metabolism. Previously, it was thought that a well-studied calcium-containing MDH (Ca-MDH) was the major pathway in bacteria for methanol oxidation. The main objective of this project is to understand why nature has chosen the lanthanides to catalyze the - for many bacteria essential - oxidation of methanol. This understanding will come from studying mechanistic aspects of methanol dehydrogenases and careful comparison of kinetic parameters at different pH, temperatures, with different lanthanides (and calcium) as well as comparing spectroscopic signatures. Specifically, we want to answer the following questions: Why do some bacteria switch from Ca-MDH to Ln-MDH, even at only nanomolar concentrations of Ln? Are Ln-MDHs better than Ca-MDH? What is the mechanism of alcohol oxidation? Why are certain lanthanides (larger, earlier Ln) better than others (later, smaller Ln) and more effective in turning over methanol?