The Alternative Route to Heme in the Methanogenic ArchaeonMethanosarcina barkeri

Archaea
2014.0

Abstract

<jats:p>In living organisms heme is formed from the common precursor uroporphyrinogen III by either one of two substantially different pathways. In contrast to eukaryotes and most bacteria which employ the so-called “classical” heme biosynthesis pathway, the archaea use an alternative route. In this pathway, heme is formed from uroporphyrinogen III via the intermediates precorrin-2, sirohydrochlorin, siroheme, 12,18-didecarboxysiroheme, and iron-coproporphyrin III. In this study the heme biosynthesis proteins AhbAB, AhbC, and AhbD from<jats:italic>Methanosarcina barkeri</jats:italic>were functionally characterized. Using an<jats:italic>in vivo</jats:italic>enzyme activity assay it was shown that AhbA and AhbB (Mbar_A1459 and Mbar_A1460) together catalyze the conversion of siroheme into 12,18-didecarboxysiroheme. The two proteins form a heterodimeric complex which might be subject to feedback regulation by the pathway end-product heme. Further, AhbC (Mbar_A1793) was shown to catalyze the formation of iron-coproporphyrin III<jats:italic>in vivo</jats:italic>. Finally, recombinant AhbD (Mbar_A1458) was produced in<jats:italic>E. coli</jats:italic>and purified indicating that this protein most likely contains two [4Fe-4S] clusters. Using an<jats:italic>in vitro</jats:italic>enzyme activity assay it was demonstrated that AhbD catalyzes the conversion of iron-coproporphyrin III into heme.

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