Multiheme selenoenzyme essential for elemental sulfur respiration

Microbial reduction of elemental sulfur is a pivotal process in the global sulfur cycle ¹ . Insoluble elemental sulfur can serve as a terminal electron acceptor during anaerobic respiration, producing sulfide ^2,3 . However, the molecular mechanisms underlying sulfur reduction remain poorly understood. Here we show that an evolutionarily conserved multiheme cytochrome c selenoprotein (MccSep) is essential for elemental sulfur reduction in a sulfur-respiring bacterium. Our biochemical and structural analyses revealed that MccSep comprises four identical subunits, each containing five c -type hemes and one selenocysteine residue (U325). The enzyme catalyzes polysulfide reduction at a unique active site, where C239 coordinates with the heme iron center, while U325 plays a crucial role in the catalytic process. Genetic analysis further revealed the critical roles of U325 and C239 in driving in vivo elemental sulfur respiration. These findings unveiled a selenium-sulfur-dependent catalytic chemistry on a heme center during polysulfide reduction, expanding the scope of biological catalysis and deepening our molecular understanding of bacterial sulfur respiration.