<p> Tetrapyrroles are large macrocyclic compounds derived from a common biosynthetic pathway [<cite idref="PUB00009744"/>]. The end-product, uroporphyrinogen III, is used to synthesise a number of important molecules, including cobalamin (vitamin B12), haem, sirohaem, chlorophyll, coenzyme F430 and phytochromobilin [<cite idref="PUB00035496"/>].</p><p> This entry represents several tetrapyrrole methylases, which consist of two non-similar domains. These enzymes catalyse the methylation of their substrates using S-adenosyl-L-methionine as a methyl source. Enzymes in this family include:</p><ul><li>Uroporphyrinogen III methyltransferase (<db_xref db="EC" dbkey="2.1.1.107"/>) (SUMT), which catalyses the conversion of uroporphyrinogen III to precorrin-2 at the first branch-point of the tetrapyrrole synthesis pathway, directing the pathway towards cobalamin or sirohaem synthesis [<cite idref="PUB00030902"/>].</li><li>Precorrin-2 C20-methyltransferase CobI/CbiL (<db_xref db="EC" dbkey="2.1.1.130"/>), which introduces a methyl group at C-20 on precorrin-2 to produce precorrin-3A during cobalamin biosynthesis. This reaction is key to the conversion of a porphyrin-type tetrapyrrole ring to a corrin ring [<cite idref="PUB00035497"/>]. In some species, this enzyme is part of a bifunctional protein.</li><li>Precorrin-4 C11-methyltransferase CobM/CbiF (<db_xref db="EC" dbkey="2.1.1.133"/>), which introduces a methyl group at C-11 on precorrin-4 to produce precorrin-5 during cobalamin biosynthesis [<cite idref="PUB00035315"/>].</li><li>Sirohaem synthase CysG (<db_xref db="EC" dbkey="2.1.1.107"/>), domains 4 and 5, which synthesizes sirohaem from uroporphyrinogen III, at the first branch-point in the tetrapyrrole biosynthetic pathway, directing the pathway towards sirohaem synthesis [<cite idref="PUB00029889"/>].</li><li>Diphthine synthase (<db_xref db="EC" dbkey="2.1.1.98"/>), which carries out the methylation step during the modification of a specific histidine residue of elongation factor 2 (EF-2) during diphthine synthesis.</li></ul> Tetrapyrrole methylase