Sprecher
Beschreibung
Lanthanide ions as catalytic cofactors - from prebiotic peptides to de novo photoenzymes
Cathleen Zeymer
Center for Functional Protein Assemblies, TUM School of Natural Sciences, Technical University of Munich (TUM), Germany
Metal ions are powerful catalysts. They serve as versatile cofactors in modern metalloenzymes, but likely also played an essential role at the origin of life. Small peptides binding the available metal ions may have substantially broadened the catalytic repertoire of the prebiotic world, for instance by mediating the formation of functional molecular assemblies, promoting Lewis acid activation of substrates, and even photoredox chemistry. Our work focusses on the 4f elements, or lanthanides, which have been added only recently to the list of enzymatic metal cofactors found in nature. We have developed a luminescence-based assay to screen libraries of peptides or proteins to identify potent lanthanide binders (1). A selection of short peptides containing only prebiotic amino acids has been tested for their ability to modulate RNA hydrolysis and ligation in the presence of lanthanide ions. Furthermore, we have developed artificial lanthanide-dependent photoredox enzymes (PhotoLanZymes). These de novo designed catalysts promote radical carbon-carbon bond cleavages upon visible-light irradiation (2). Computational protein design and directed evolution were combined to obtain enantioselective enzymes variants (3). Overall, the talk will highlight the catalytic potential of lanthanide-binding peptides and proteins for various types of chemistries.
(1) R. Klassen, A. Heider, H. Kugler, M. Groll, C. Zeymer, "A Luminescence-Based Screening Platform for Lanthanide-Binding Peptides and Proteins" ACS Chemical Biology 2025, 20, 2897-2906. https://doi.org/10.1021/acschembio.5c00670
(2) A. S. Klein, F. Leiss-Maier, R. Mühlhofer, B. Boesen, G. Mustafa, H. Kugler, C. Zeymer, "A De Novo Metalloenzyme for Cerium Photoredox Catalysis" J. Am. Chem. Soc. 2024, 146, 25976-25985. https://doi.org/10.1021/jacs.4c04618
(3) F. Leiss-Maier, J. Behringer, G. Mustafa, A. Heider, R. Mühlhofer, A. S. S. Klein, M. Groll, C. Zeymer, "Computational redesign and directed evolution of a lanthanide-dependent photoredox enzyme for enantioselective diol cleavage" Chem. Sci. 2026, accepted. https://doi.org/10.1039/D5SC08010J