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Escherichia coli K-12 substr. MG1655 Pathway: heme biosynthesis II (anaerobic)

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Locations of Mapped Genes:

Genetic Regulation Schematic: ?

Superclasses: Biosynthesis Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis Porphyrin Compounds Biosynthesis Heme Biosynthesis

Summary:
General Background

In prokaryotes and eukaryotes heme (protoheme IX, protoheme, heme b) is an iron-containing prosthetic group found in many essential proteins including cytochromes and heme-containing globins. In addition to its role in oxidative metabolism, heme also functions as a regulatory molecule in transcription, translation, protein targeting, protein stability, and cellular differentiation. Heme is a porphyrin member of the cyclic tetrapyrroles. Even though it is biosynthesized as protoheme IX, different derivatives of protoheme IX can be formed that differ in modifications to the porphyrin ring, including the way it is bound to the protein, such as heme o, heme a, heme c, and heme d.

In various organisms important branch points within the heme biosynthetic pathway lead to the biosynthesis of other important compounds such as vitamin B12 (cobalamin) (see MetaCyc pathway adenosylcobalamin biosynthesis II (late cobalt incorporation)), coenzyme F430 (see MetaCyc pathway factor 430 biosynthesis), siroheme (see EcoCyc pathway siroheme biosynthesis), heme D (see EcoCyc reaction heme b + hydrogen peroxide = heme d), and bacteriochlorophyll (see MetaCyc pathway chlorophyllide a biosynthesis I (aerobic, light-dependent)).

In Escherichia coli heme biosynthesis begins with L-glutamate and proceeds through 5-amino-levulinate (the universal tetrapyrrole precursor) to uroporphyrinogen III as shown in the tetrapyrrole biosynthesis I (from glutamate) pathway link. Uroporphyrinogen III is converted to protoheme IX in the pathway shown here. Subsequent reactions that produce heme o and heme d are shown in the reaction links. In E. coli hemes c, d, and o function as the prosthetic groups for c-type cytochromes, cytochrome bd, and cytochrome bo, respectively. The c-type cytochromes are synthesized only anaerobically in the presence of nitrogenous electron acceptors. Cytochrome bd, and cytochrome bo are O2-reducing terminal oxidase complexes.

Although regulation of heme biosynthesis is not well studied in E. coli, evidence suggests that the cellular level of free protoheme IX controls the rate of heme synthesis at the level of formation of glutamate-1-semialdehyde by glutamyl-tRNA reductase encoded by hemA (see EcoCyc pathway tetrapyrrole biosynthesis I (from glutamate)).

Review: Beale, S.I. (2007) "Biosynthesis of Hemes" EcoSal 3.6.3.11 [ECOSAL]

Reviews: [Frankenberg03, Panek02, Obornik05, Layer10]

About This Pathway

The pathway shown here from uroporphyrinogen III to protoheme IX is a segment of the overall heme biosynthetic pathway. The pathway links at the beginning and end of this pathway show the preceding and succeeding steps. The main difference between this protoheme biosynthetic pathway and the pathway shown in heme biosynthesis I (aerobic) is the presence of the enzyme coproporphyrinogen III dehydrogenase (EC 1.3.99.22), which can catalyze the transition from coproporphyrinogen III to protoporphyrinogen IX without the need for molecular oxygen. This enzyme is found in many bacteria, but has not been verified to be present in archaea or eukaryotes.

In this pathway the four acetate groups of uroporphyrinogen III are sequentially decarboxylated and the methyl groups from these four acetates remain in coproporphyrinogen III. Two propionate groups at positions 3 and 8 of coproporphyrinogen III are decarboxylated to vinyl groups. In the facultatively aerobic E. coli and Salmonella enterica subsp. enterica serovar Typhimurium, the O2-independent enzyme coproporphyrinogen dehydrogenase encoded by gene hemN can function under anaerobic conditions. HemN contains an O2-sensitive iron-sulfur cluster [Layer03]. Under aerobic conditions the O2-requiring product of gene hemF produces protoporphyrinogen IX [Breckau03] (see pathway heme biosynthesis I (aerobic)).

In the next step six electrons are removed from protoporphyrinogen IX by a membrane-associated oxidase encoded by gene hemG forming protoporphyrin IX. In E. coli under anaerobic conditions this oxidation is coupled to the reduction of nitrate or fumarate. Under aerobic conditions this enzyme uses O2 as electron acceptor [Mobius10, Jacobs78] (see pathway heme biosynthesis I (aerobic)). The final step forming heme (protoheme IX) is catalyzes by ferrichelatase which inserts Fe2+ into protoporphyrin IX.

Review: Beale, S.I. (2007) "Biosynthesis of Hemes" EcoSal 3.6.3.11 [ECOSAL]

Superpathways: superpathway of heme biosynthesis from uroporphyrinogen-III

Variants: heme biosynthesis I (aerobic)

Credits:
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
Last-Curated ? 08-Jun-2011 by Fulcher C , SRI International


References

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

ECOSAL: "Escherichia coli and Salmonella: Cellular and Molecular Biology." Online edition.

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

Jacobs78: Jacobs NJ, Jacobs JM (1978). "Quinones as hydrogen carriers for a late step in anaerobic heme biosynthesis in Escherichia coli." Biochim Biophys Acta 544(3);540-6. PMID: 365243

Layer03: Layer G, Moser J, Heinz DW, Jahn D, Schubert WD (2003). "Crystal structure of coproporphyrinogen III oxidase reveals cofactor geometry of Radical SAM enzymes." EMBO J 22(23);6214-24. PMID: 14633981

Layer10: Layer G, Reichelt J, Jahn D, Heinz DW (2010). "Structure and function of enzymes in heme biosynthesis." Protein Sci 19(6);1137-61. PMID: 20506125

Mobius10: Mobius K, Arias-Cartin R, Breckau D, Hannig AL, Riedmann K, Biedendieck R, Schroder S, Becher D, Magalon A, Moser J, Jahn M, Jahn D (2010). "Heme biosynthesis is coupled to electron transport chains for energy generation." Proc Natl Acad Sci U S A 107(23);10436-41. PMID: 20484676

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

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

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

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

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.

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

Jacobs76: Jacobs NJ, Jacobs JM (1976). "Nitrate, fumarate, and oxygen as electron acceptors for a late step in microbial heme synthesis." Biochim Biophys Acta 449(1);1-9. PMID: 788792

Jacobs77: Jacobs NJ, Jacobs JM (1977). "Evidence for involvement of the electron transport system at a late step of anaerobic microbial heme synthesis." Biochim Biophys Acta 459(1);141-4. PMID: 318855

Jacobs84: Jacobs JM, Jacobs NJ (1984). "Protoporphyrinogen oxidation, an enzymatic step in heme and chlorophyll synthesis: partial characterization of the reaction in plant organelles and comparison with mammalian and bacterial systems." Arch Biochem Biophys 229(1);312-9. PMID: 6703698

Layer02: Layer G, Verfurth K, Mahlitz E, Jahn D (2002). "Oxygen-independent coproporphyrinogen-III oxidase HemN from Escherichia coli." J Biol Chem 2002;277(37);34136-42. PMID: 12114526

Layer04: Layer G, Heinz DW, Jahn D, Schubert WD (2004). "Structure and function of radical SAM enzymes." Curr Opin Chem Biol 8(5);468-76. PMID: 15450488

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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