Heme Degradation by <i>Staphylococcus aureus</i> IsdG and IsdI Liberates Formaldehyde Rather Than Carbon Monoxide

IsdG and IsdI from <i>Staphylococcus aureus</i> are novel heme-degrading enzymes containing unusually nonplanar (ruffled) heme. While canonical heme-degrading enzymes, heme oxygenases, catalyze heme degradation coupled with the release of CO, in this study we demonstrate that the primary C1 product of the <i>S. aureus</i> enzymes is formaldehyde. This finding clearly reveals that both IsdG and IsdI degrade heme by an unusual mechanism distinct from the well-characterized heme oxygenase mechanism as recently proposed for MhuD from <i>Mycobacterium tuberculosis</i>. We conclude that heme ruffling is critical for the drastic mechanistic change for these novel bacterial enzymes