The <i>Escherichia coli cysG</i> gene encodes the multifunctional protein, siroheme synthase

Previously, the E. coli cysG gene product had been shown to sequentially methylate uro'gen III to produce precorrin-2, hence it was given the trivial name uro'gen III methylase. We now report that in addition to methylase activity, the CysG protein catalyses both the NAD+ dependent oxidation of precorrin-2 to sirohydrochlorin, but also the insertion of iron into this oxidized intermediate, thereby producing siroheme. Thus CysG is a multifunctional protein solely responsible for siroheme synthesis from uro'gen III in E. coli, and accordingly is renamed siroheme synthase.