Updated BioCyc iOS App now
available in iTunes store
Updated BioCyc iOS App now
available in iTunes store
Updated BioCyc iOS App now
available in iTunes store
Updated BioCyc iOS App now
available in iTunes store
Updated BioCyc iOS App now
available in iTunes store

MetaCyc Pathway: heme biosynthesis II (anaerobic)
Inferred from experiment

Enzyme View:

Pathway diagram: heme biosynthesis II (anaerobic)

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: BiosynthesisCofactors, Prosthetic Groups, Electron Carriers BiosynthesisPorphyrin Compounds BiosynthesisHeme Biosynthesis

Some taxa known to possess this pathway include : Anabaena variabilis, Aquifex aeolicus, Bacillus subtilis, Bradyrhizobium japonicum, Cupriavidus necator, Escherichia coli K-12 substr. MG1655, Halorhodospira halophila, Helicobacter pylori, Lactococcus lactis, Mycobacterium tuberculosis, Nitrosococcus oceani, Nitrosospira multiformis, Penicillium janthinellum, Pseudomonas aeruginosa, Salmonella enterica enterica serovar Typhi, Streptococcus sanguinis, Synechocystis sp. PCC 6803, Tetrahymena thermophila

Expected Taxonomic Range: Alveolata, Bacteria , Fungi

Heme (protoheme, heme b) is an iron-containing prosthetic group found in many essential proteins including cytochromes and heme-containing globins. It is a porphyrin member of the cyclic tetrapyrroles. It is biosynthesized as protoheme, but different derivatives of protoheme can be formed that differ in modifications to the porphyrin ring, including how it is bound to the protein, such as heme o, heme a, heme c, and heme d.

The main difference between this protoheme biosynthetic pathway and the one shown at heme biosynthesis I (aerobic) is the presence of the enzyme coproporphyrinogen III dehydrogenase (EC, which catalyzes the transition from coproporphyrinogen III to protoporphyrinogen IX without the need for molecular oxygen. In addition, the enzyme protoporphyrinogen oxidase, which under aerobic conditions catalyzes the oxidation of protoporphyrinogen IX to protoporphyrin IX using molecular oxygen (EC, catalyzes this transition under anaerobic conditions using a quinone instead of molecular oxygen (EC

Coproporphyrinogen III dehydrogenase (EC is found in many bacteria, but does not appear to be present in archaea or eukarya (the only reference for its presence in a eukaryote is in the organism Tetrahymena thermophila, but this finding is based on sequence analysis alone, and has not been verified biochemically).

Important branch points within this pathway lead to biosynthesis of other important compounds such as vitamin B12 (cobalamin) (see adenosylcobalamin biosynthesis II (aerobic)), oxidized coenzyme F430 (see factor 430 biosynthesis), siroheme (see siroheme biosynthesis), heme D biosynthesis, and bacteriochlorophyll (see chlorophyllide a biosynthesis I (aerobic, light-dependent)).

This topic has been reviewed in [Frankenberg03, Panek02, Obornik05].

Superpathways: superpathway of heme biosynthesis from uroporphyrinogen-III

Variants: heme biosynthesis I (aerobic), heme biosynthesis III (from siroheme), heme d1 biosynthesis, superpathay of heme biosynthesis from glutamate, superpathway of heme biosynthesis from glycine

Unification Links: EcoCyc:HEMESYN2-PWY

Created 11-Dec-1995 by Riley M, Marine Biological Laboratory
Revised 19-Jun-2006 by Caspi R, SRI International
Revised 09-Jul-2009 by Keseler I, SRI International


Caughey75: Caughey WS, Smythe GA, O'Keeffe DH, Maskasky JE, Smith MI (1975). "Heme A of cytochrome c oxicase. Structure and properties: comparisons with hemes B, C, and S and derivatives." J Biol Chem 250(19);7602-22. PMID: 170266

Frankenberg03: Frankenberg N, Moser J, Jahn D (2003). "Bacterial heme biosynthesis and its biotechnological application." Appl Microbiol Biotechnol 63(2);115-27. PMID: 13680202

Obornik05: Obornik M, Green BR (2005). "Mosaic origin of the heme biosynthesis pathway in photosynthetic eukaryotes." Mol Biol Evol 22(12);2343-53. PMID: 16093570

Panek02: Panek H, O'Brian MR (2002). "A whole genome view of prokaryotic haem biosynthesis." Microbiology 148(Pt 8);2273-82. PMID: 12177321

Troup95: Troup B, Hungerer C, Jahn D (1995). "Cloning and characterization of the Escherichia coli hemN gene encoding the oxygen-independent coproporphyrinogen III oxidase." J Bacteriol 1995;177(11);3326-31. PMID: 7768836

Warburg51: Warburg O, Gewitz HS (1951). "Cytohamin aus Herzmuskel." Hoppe-Seyler´s Zeitschrift für physiologische Chemie 288(1);1-4.

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Boynton09: Boynton TO, Daugherty LE, Dailey TA, Dailey HA (2009). "Identification of Escherichia coli HemG as a novel, menadione-dependent flavodoxin with protoporphyrinogen oxidase activity." Biochemistry 48(29):6705-11. PMID: 19583219

Breckau03: Breckau D, Mahlitz E, Sauerwald A, Layer G, Jahn D (2003). "Oxygen-dependent coproporphyrinogen III oxidase (HemF) from Escherichia coli is stimulated by manganese." J Biol Chem 278(47);46625-31. PMID: 12975365

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

Cantoni84: Cantoni L, Dal Fiume D, Ruggieri R (1984). "Decarboxylation of uroporphyrinogen I and III in 2,3,7,8-tetrachlorodibenzo-p-dioxin induced porphyria in mice." Int J Biochem 16(5);561-5. PMID: 6724109

Collins81: Collins MD, Jones D (1981). "Distribution of isoprenoid quinone structural types in bacteria and their taxonomic implication." Microbiol Rev 45(2);316-54. PMID: 7022156

Dailey00: Dailey HA, Dailey TA, Wu CK, Medlock AE, Wang KF, Rose JP, Wang BC (2000). "Ferrochelatase at the millennium: structures, mechanisms and [2Fe-2S] clusters." Cell Mol Life Sci 57(13-14);1909-26. PMID: 11215517

Dailey02: Dailey TA, Dailey HA (2002). "Identification of [2Fe-2S] clusters in microbial ferrochelatases." J Bacteriol 184(9);2460-4. PMID: 11948160

Dailey86: Dailey HA (1986). "Purification and characterization of bacterial ferrochelatase." Methods Enzymol 123;408-15. PMID: 3702737

Dailey94: Dailey HA, Sellers VM, Dailey TA (1994). "Mammalian ferrochelatase. Expression and characterization of normal and two human protoporphyric ferrochelatases." J Biol Chem 269(1);390-5. PMID: 8276824

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Frey01: Frey PA (2001). "Radical mechanisms of enzymatic catalysis." Annu Rev Biochem 70;121-48. PMID: 11395404

Frey08: Frey PA, Hegeman AD, Ruzicka FJ (2008). "The Radical SAM Superfamily." Crit Rev Biochem Mol Biol 43(1);63-88. PMID: 18307109

Frustaci93: Frustaci JM, O'Brian MR (1993). "The Escherichia coli visA gene encodes ferrochelatase, the final enzyme of the heme biosynthetic pathway." J Bacteriol 175(7);2154-6. PMID: 8458858

Fujimoto12: Fujimoto N., Kosaka T., Yamada M. (2012). "Menaquinone as Well as Ubiquinone as a Crucial Component in the Escherichia coli Respiratory Chain." Chapter 10 in Chemical Biology, edited by D Ekinci, ISBN 978-953-51-0049-2.

Gaudet10: Gaudet P, Livstone M, Thomas P (2010). "Annotation inferences using phylogenetic trees." PMID: 19578431

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Ineichen93: Ineichen G, Biel AJ (1993). "Location of the hemE gene on the physical map of Escherichia coli." J Bacteriol 175(23);7749-50. PMID: 8244953

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Showing only 20 references. To show more, press the button "Show all references".

Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by Pathway Tools version 19.5 (software by SRI International) on Fri Apr 29, 2016, biocyc13.