Spectroscopic and Mechanistic Studies of Rare Earth Element Dependent Enzymes

• Applicant: Professorin Dr. Lena Daumann
• Subject Area: Biological and Biomimetic Chemistry ; Biochemistry
• Term: since 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 392552271

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?

• DFG Programme: Research Grants