IUBMB Enzyme Nomenclature


Accepted name: heme a synthase

Reaction: ferroheme o + H2O + 2 acceptor = ferroheme a + 2 reduced acceptor (overall reaction)
(1a) ferroheme o + H2O + acceptor = ferroheme i + reduced acceptor
(1b) ferroheme i + H2O + acceptor = hydroxyferroheme i + reduced acceptor
(1c) hydroxyferroheme i = ferroheme a + H2O (spontaneous)

Other name(s): COX15 (gene name); ctaA (gene name)

Systematic name: ferroheme o:acceptor C-81-oxidoreductase (heme a-forming)

Comments: Contains a heme b cofactor. The enzyme catalyses the conversion of heme o to heme a by two successive hydroxylations of the methyl group at C-8, using water as the oxygen source. The first hydroxylation forms heme i, the second hydroxylation results in an unstable dihydroxymethyl group, which spontaneously dehydrates, resulting in the formyl group of heme a [2,4]. The electrons produced by the reaction are transferred to a heme b cofactor [6]. However, the electron acceptor that is used to restore the heme b cofactor to its oxidized state is still not known (both a thioredoxin-like protein and menaquinol have been proposed).

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:


1. Barros, M.H., Carlson, C.G., Glerum, D.M. and Tzagoloff, A. Involvement of mitochondrial ferredoxin and Cox15p in hydroxylation of heme O. FEBS Lett. 492 (2001) 133-138. [PMID: 11248251]

2. Brown, K.R., Allan, B.M., Do, P. and Hegg, E.L. Identification of novel hemes generated by heme A synthase: evidence for two successive monooxygenase reactions. Biochemistry 41 (2002) 10906-10913. [PMID: 12206660]

3. Brown, K.R., Brown, B.M., Hoagland, E., Mayne, C.L. and Hegg, E.L. Heme A synthase does not incorporate molecular oxygen into the formyl group of heme A. Biochemistry 43 (2004) 8616-8624. [PMID: 15236569]

4. Hederstedt, L., Lewin, A. and Throne-Holst, M. Heme A synthase enzyme functions dissected by mutagenesis of Bacillus subtilis CtaA. J. Bacteriol. 187 (2005) 8361-8369. [PMID: 16321940]

5. Hederstedt, L. Heme A biosynthesis. Biochim. Biophys. Acta 1817 (2012) 920-927. [PMID: 22484221]

6. Niwa, S., Takeda, K., Kosugi, M., Tsutsumi, E., Mogi, T. and Miki, K. Crystal structure of heme A synthase from Bacillus subtilis. Proc. Natl. Acad. Sci. USA 115 (2018) 11953-11957. [PMID: 30397130]

[EC created 2020]

Return to EC 1.17.99 home page
Return to EC 1.17 home page
Return to EC 1 home page
Return to Enzymes home page
Return to IUBMB Biochemical Nomenclature home page