Siroheme

Siroheme is a heme-like prosthetic group found in a subset of iron-sulfur and nitrogen/sulfur metabolism enzymes. It is a modified tetrapyrrole derived from sirohydrochlorin, in which an iron ion is inserted into the macrocycle to form siroheme. The iron is coordinated within the porphyrin ring by the protein matrix, with axial ligands supplied by amino acid side chains that vary among enzymes.

Siroheme occurs primarily in nitrite reductases and sulfite reductases, where it participates in the six-electron reductions of nitrite to ammonium and sulfite to sulfide, respectively. These reactions are central to assimilatory and dissimilatory pathways for nitrogen and sulfur metabolism in many bacteria, archaea, and some photosynthetic eukaryotes. The cofactor enables efficient electron transfer and substrate reduction within the active sites of these enzymes.

Biosynthesis of siroheme proceeds from sirohydrochlorin, with iron insertion catalyzed by a sirohydrochlorin ferrochelatase enzyme. In many organisms this cofactor biosynthetic route intersects with the broader heme biosynthesis pathway, linking siroheme production to cellular iron and nitrogen-sulfur metabolism. The exact enzymatic steps and their genetic organization vary among species, but the core concept is iron insertion into a reduced tetrapyrrole framework to yield the active siroheme cofactor.

Siroheme is distinct from cobalamin and from canonical heme b, yet it shares the underlying tetrapyrrole chemistry that underpins many redox-active cofactors in biology.