Evidence for lanthanide and PQQ dependent dehydrogenases in Eukarya

Abstract

Lanthanides function as enzyme cofactors in bacteria, where they are widely distributed in pyrroloquinoline quinone-dependent 8-bladed beta-propeller dehydrogenases. No lanthanide-dependent enzymes, however, have been described outside prokaryotes. Here, we combined structural bioinformatics, phylogenetics, AlphaFold3 co-folding, coordination-sphere comparison, and quantum-mechanical cluster modeling to search for and rank putative lanthanide-coordinating 8-bladed beta-propeller enzymes in Eukarya. We identified candidate lanthanide-coordinating proteins in a diverse range of eukaryotes, predominantly plants and fungi, including species of clear industrial and agricultural relevance. A high-confidence subset matched validated bacterial Ln-binders based on both geometric similarity to canonical Ln-binding sites and on predicted Ln3+ versus Ca2+ selectivity. Our findings indicate that lanthanide biology likely extends beyond bacteria, with implications for plant, fungal, and broader eukaryotic metabolism, and warrant targeted biochemical investigation.