Spectroscopic and Mechanistic Studies of Rare Earth Element Dependent Enzymes

镧系元素（Ln），即周期表中的镧至镥元素，在自然界中丰富，但由于其低溶解度，生物利用度很差。然而，许多细菌在生化过程中使用这些元素。更具体地，细菌利用三价Ln如镧和钕作为甲醇脱氢酶（MDH）活性位点中的辅因子，所述甲醇脱氢酶催化甲醇氧化成甲醛作为其一碳（C1）能量代谢的一部分。以前，人们认为，一个充分研究的含钙MDH（Ca-MDH）是在细菌中的甲醇氧化的主要途径。这个项目的主要目标是了解为什么大自然选择镧系元素来催化甲醇的氧化-对于许多细菌来说是必不可少的。这种理解将来自于研究甲醇脱氢酶的机制方面，以及在不同pH、温度、不同镧系元素（和钙）下仔细比较动力学参数，以及比较光谱特征。具体来说，我们想回答以下问题：为什么有些细菌从Ca-MDH切换到Ln-MDH，即使只有纳摩尔浓度的Ln？Ln-MDH比Ca-MDH好吗？酒精氧化的机理是什么？为什么某些镧系元素（较大、较早的Ln）比其他元素（较晚、较小的Ln）更好，并且在转化甲醇方面更有效？

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?