Giant viruses encode vitamin K–based redox modules for lipid modification

Here we report the discovery and functional reconstitution of viral homologs of vitamin K epoxide reductase (VKOR) encoded by giant viruses. Using phylogenetic and genomic context analysis, we find that viral VKOR genes are frequently located adjacent to -carboxylase-like epoxidase and fatty acid desaturase domains, consistent with a putative modular redox pathway for membrane lipid modification.

To investigate their function, we expressed viral VKORs in an Escherichia coli strain lacking disulfide bond–forming enzymes and examined both their membrane topology and activity. Remarkably, a minimal set of residue substitutions enabled proper membrane insertion and restored bacterial motility, demonstrating that viral VKORs are catalytically competent electron shuttles. Structural modeling supports their integration into the endoplasmic reticulum–like environment in the host.