Biosynthesis and Insertion of Heme

  • Katrin Müller
  • Toni Mingers
  • V. Haskamp
  • Dieter Jahn
  • Martina JahnEmail author
Reference work entry
Part of the Handbook of Hydrocarbon and Lipid Microbiology book series (HHLM)


The red, iron containing tetrapyrrole heme is an essential cofactor of enzymes involved in the electron transport chain of energy generation and used for catalyzing chemically challenging reactions of the metabolism. It is also used for diatomic gas transport (O2, CO, CO2, NO, N2O), catalysis, and detection. Multiple transcriptional regulators and transporters bind heme. This chapter focuses on the highly unusual pathways for heme biosynthesis and the integration of protoheme into target proteins. Today, three different biosynthetic routes for heme formation are known. The general precursor molecule of all tetrapyrroles 5-aminolevulinic acid is formed by two different pathways starting either with glutamyl-tRNA or succinyl-CoA and glycine. The conversion of 5-aminolevulinic acid to uroporphyrinogen III is common to all biosynthetic paths. Then the pathway branches to a classical route via protoporphyrin and two currently known alternative routes via coproporpyhrin III and siroheme. Various steps are catalyzed by up to three structurally unrelated enzymes. Finally, formed protoheme (heme b) gets actively inserted into proteins by the “Radical SAM” protein HemW. A detailed description of involved intermediates, enzymes, and their mechanisms are depicted below.



We thank Stefan Barthels for his excellent technical assistance and are indebted to the Deutsche Forschungsgemeinschaft (GRK 2223, PROCOMPAS) for funding.


  1. Abicht HK, Martinez J, Layer G, Jahn D, Solioz M (2012) Lactococcus lactis HemW (HemN) is a haem-binding protein with a putative role in haem trafficking. Biochem J 442(2):335–343PubMedCrossRefGoogle Scholar
  2. Akhtar M (2003) Coproporphyrinogen III and protoporphyrinogen IX oxidases. In: Kadish KM, Smith KM, Guilard R (eds) The porphyrin handbook, vol 12, the iron and cobalt pigments: biosynthesis, structure and degradation. Elsevier, New York, pp 75–92Google Scholar
  3. Anderson PJ, Entsch B, McKay DB (2001) A gene, cobA + hemD, from Selenomonas ruminantium encodes a bifunctional enzyme involved in the synthesis of vitamin B12. Gene 281(1–2):63–70PubMedCrossRefGoogle Scholar
  4. Ashenbrucker H, Cartwright GE, Goldberg A, Wintrobe MM (1956) Studies on the biosynthesis of heme in vitro by avian erythrocytes. Blood 11(9):821–833PubMedGoogle Scholar
  5. Astner I, Schulze JO, van den Heuvel J, Jahn D, Schubert WD, Heinz DW (2005) Crystal structure of 5-aminolevulinate synthase, the first enzyme of heme biosynthesis, and its link to XLSA in humans. EMBO J 24(18):3166–3177PubMedPubMedCentralCrossRefGoogle Scholar
  6. Azim N, Deery E, Warren MJ, Wolfenden BA, Erskine P, Cooper JB, Coker A, Wood SP, Akhtar M (2014) Structural evidence for the partially oxidized dipyrromethene and dipyrromethanone forms of the cofactor of porphobilinogen deaminase: structures of the Bacillus megaterium enzyme at near-atomic resolution. Acta Crystallogr D Biol Crystallogr 70(Pt 3):744–751PubMedPubMedCentralCrossRefGoogle Scholar
  7. Bali S, Lawrence AD, Lobo SA, Saraiva LM, Golding BT, Palmer DJ, Howard MJ, Ferguson SJ, Warren MJ (2011) Molecular hijacking of siroheme for the synthesis of heme and d1 heme. Proc Natl Acad Sci USA 108(45):18260–18265PubMedCrossRefPubMedCentralGoogle Scholar
  8. Bali S, Palmer DJ, Schroeder S, Ferguson SJ, Warren MJ (2014) Recent advances in the biosynthesis of modified tetrapyrroles: the discovery of an alternative pathway for the formation of heme and heme d1. Cell Mol Life Sci 71(15):2837–2863PubMedCrossRefPubMedCentralGoogle Scholar
  9. Battersby AR, Fookes CJR, Matcham GWJ, McDonald E (1979) Order of assembly of the four pyrrole rings during biosynthesis of the natural porphyrins. J Chem Soc Chem Commun 0:539–541CrossRefGoogle Scholar
  10. Beale SI, Castelfranco PA (1973) 14C incorporation from exogenous compounds into delta-aminolevulinic acid by greening cucumber cotyledons. Biochem Biophys Res Commun 52(1):143–149PubMedCrossRefPubMedCentralGoogle Scholar
  11. Blanche F, Debussche L, Thibaut D, Crouzet J, Cameron B (1989) Purification and characterization of S-adenosyl-l-methionine: uroporphyrinogen III methyltransferase from Pseudomonas denitrificans. J Bacteriol 171(8):4222–4231PubMedPubMedCentralCrossRefGoogle Scholar
  12. Bogorad L (1958) The enzymatic synthesis of porphyrins from porphobilinogen. II. Uroporphyrin III. J Biol Chem 233(2):510–515PubMedPubMedCentralGoogle Scholar
  13. Bogorad L, Granick S (1953) The enzymatic synthesis of porphyrins from porphobilinogen. Proc Natl Acad Sci USA 39(12):1176–1188PubMedCrossRefPubMedCentralGoogle Scholar
  14. Bollivar DW, Clauson C, Lighthall R, Forbes S, Kokona B, Fairman R, Kundrat L, Jaffe EK (2004) Rhodobacter capsulatus porphobilinogen synthase, a high activity metal ion independent hexamer. BMC Biochem 5:17PubMedPubMedCentralCrossRefGoogle Scholar
  15. Boss L, Oehme R, Billig S, Birkemeyer C, Layer G (2017) The radical SAM enzyme NirJ catalyzes the removal of two propionate side chains during heme d1 biosynthesis. FEBS J 284(24):4314–4327PubMedCrossRefPubMedCentralGoogle Scholar
  16. 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):6705–6711PubMedPubMedCentralCrossRefGoogle Scholar
  17. Boynton TO, Gerdes S, Craven SH, Neidle EL, Phillips JD, Dailey HA (2011) Discovery of a gene involved in a third bacterial protoporphyrinogen oxidase activity through comparative genomic analysis and functional complementation. Appl Environ Microbiol 77(14):4795–4801PubMedPubMedCentralCrossRefGoogle Scholar
  18. 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):46625–46631PubMedCrossRefPubMedCentralGoogle Scholar
  19. Breinig S, Kervinen J, Stith L, Wasson AS, Fairman R, Wlodawer A, Zdanov A, Jaffe EK (2003) Control of tetrapyrrole biosynthesis by alternate quaternary forms of porphobilinogen synthase. Nat Struct Biol 10(9):757–763PubMedCrossRefGoogle Scholar
  20. Bröcker M, Jahn D, Moser J (2012) Key enzymes of chlorophyll biosynthesis. In: Kadish K, Smith K, Guilard R (eds) World Scientific Publishing Co., Singapore Vol. 20, 1–43Google Scholar
  21. Brown BL, Kardon JR, Sauer RT, Baker TA (2018) Structure of the mitochondrial aminolevulinic acid synthase, a key heme biosynthetic enzyme. Structure 26(4):580–589.e584PubMedCrossRefPubMedCentralGoogle Scholar
  22. Buchenau B, Kahnt J, Heinemann IU, Jahn D, Thauer RK (2006) Heme biosynthesis in Methanosarcina barkeri via a pathway involving two methylation reactions. J Bacteriol 188(24):8666–8668PubMedPubMedCentralCrossRefGoogle Scholar
  23. Bung N, Roy A, Chen B, Das D, Pradhan M, Yasuda M, New MI, Desnick RJ, Bulusu G (2018) Human hydroxymethylbilane synthase: molecular dynamics of the pyrrole chain elongation identifies step-specific residues that cause AIP. Proc Natl Acad Sci USA 115(17):E4071–E4080PubMedCrossRefPubMedCentralGoogle Scholar
  24. Burton G, Fagerness PE, Hosozawa S, Jordan PM, Scott AI (1979) 13C NMR evidence for a new intermediate, pre-uroporphyrinogen, in the enzymic transformation of porphobilinogen into uroporphyrinogens I and III. J Chem Soc Chem Commun 1:202–204CrossRefGoogle Scholar
  25. Cavaleiro JA, Kenner GW, Smith KM (1974) Pyrroles and related compounds. XXXII. Biosynthesis of protoporphyrin-IX from coproporphyrinogen-3. J Chem Soc Perkin 1 10:1188–1194PubMedCrossRefPubMedCentralGoogle Scholar
  26. Celis AI, Streit BR, Moraski GC, Kant R, Lash TD, Lukat-Rodgers GS, Rodgers KR, DuBois JL (2015) Unusual peroxide-dependent, heme-transforming reaction catalyzed by HemQ. Biochemistry 54(26):4022–4032PubMedPubMedCentralCrossRefGoogle Scholar
  27. Celis AI, Gauss GH, Streit BR, Shisler K, Moraski GC, Rodgers KR, Lukat-Rodgers GS, Peters JW, DuBois JL (2017) Structure-based mechanism for oxidative decarboxylation reactions mediated by amino acids and heme propionates in coproheme decarboxylase (HemQ). J Am Chem Soc 139(5):1900–1911PubMedPubMedCentralCrossRefGoogle Scholar
  28. Corradi HR, Corrigall AV, Boix E, Mohan CG, Sturrock ED, Meissner PN, Acharya KR (2006) Crystal structure of protoporphyrinogen oxidase from Myxococcus xanthus and its complex with the inhibitor acifluorfen. J Biol Chem 281(50):38625–38633PubMedPubMedCentralCrossRefGoogle Scholar
  29. Corrigall AV, Siziba KB, Maneli MH, Shephard EG, Ziman M, Dailey TA, Dailey HA, Kirsch RE, Meissner PN (1998) Purification of and kinetic studies on a cloned protoporphyrinogen oxidase from the aerobic bacterium Bacillus subtilis. Arch Biochem Biophys 358(2):251–256PubMedCrossRefPubMedCentralGoogle Scholar
  30. Czarnecki O, Grimm B (2013) New insights in the topology of the biosynthesis of 5-aminolevulinic acid. Plant Signal Behav 8(2):e23124PubMedPubMedCentralCrossRefGoogle Scholar
  31. Dailey HA, Gerdes S, Dailey TA, Burch JS, Phillips JD (2015) Noncanonical coproporphyrin-dependent bacterial heme biosynthesis pathway that does not use protoporphyrin. Proc Natl Acad Sci USA 112(7):2210–2215PubMedCrossRefPubMedCentralGoogle Scholar
  32. Dailey HA, Dailey TA, Gerdes S, Jahn D, Jahn M, O’Brian MR, Warren MJ (2017) Prokaryotic heme biosynthesis: multiple pathways to a common essential product. Microbiol Mol Biol Rev 81(1) pii: e00048-16Google Scholar
  33. Dresel EI, Falk JE (1953) Conversion of alpha-aminolaevulinic acid to porphobilinogen in a tissue system. Nature 172(4391):1185PubMedCrossRefPubMedCentralGoogle Scholar
  34. Elder GH, Evans JO (1978) Evidence that the coproporphyrinogen oxidase activity of rat liver is situated in the intermembrane space of mitochondria. Biochem J 172(2):345–347PubMedPubMedCentralCrossRefGoogle Scholar
  35. Erskine PT, Senior N, Awan S, Lambert R, Lewis G, Tickle IJ, Sarwar M, Spencer P, Thomas P, Warren MJ et al (1997) X-ray structure of 5-aminolaevulinate dehydratase, a hybrid aldolase. Nat Struct Biol 4(12):1025–1031PubMedCrossRefPubMedCentralGoogle Scholar
  36. Fan J, Liu Q, Hao Q, Teng M, Niu L (2007) Crystal structure of uroporphyrinogen decarboxylase from Bacillus subtilis. J Bacteriol 189(9):3573–3580PubMedCrossRefGoogle Scholar
  37. Frankenberg N, Erskine PT, Cooper JB, Shoolingin-Jordan PM, Jahn D, Heinz DW (1999) High resolution crystal structure of a Mg2+-dependent porphobilinogen synthase. J Mol Biol 289(3):591–602PubMedCrossRefGoogle Scholar
  38. Frere F, Schubert WD, Stauffer F, Frankenberg N, Neier R, Jahn D, Heinz DW (2002) Structure of porphobilinogen synthase from Pseudomonas aeruginosa in complex with 5-fluorolevulinic acid suggests a double Schiff base mechanism. J Mol Biol 320(2):237–247PubMedCrossRefGoogle Scholar
  39. Frere F, Reents H, Schubert WD, Heinz DW, Jahn D (2005) Tracking the evolution of porphobilinogen synthase metal dependence in vitro. J Mol Biol 345(5):1059–1070PubMedCrossRefGoogle Scholar
  40. Gibson KD, Laver WG, Neuberger A (1958) Initial stages in the biosynthesis of porphyrins. 2. The formation of delta-aminolaevulic acid from glycine and succinyl-coenzyme A by particles from chicken erythrocytes. Biochem J 70(1):71–81PubMedPubMedCentralCrossRefGoogle Scholar
  41. Gill R, Kolstoe SE, Mohammed F, Al DBA, Mosely JE, Sarwar M, Cooper JB, Wood SP, Shoolingin-Jordan PM (2009) Structure of human porphobilinogen deaminase at 2.8 A: the molecular basis of acute intermittent porphyria. Biochem J 420(1):17–25PubMedCrossRefPubMedCentralGoogle Scholar
  42. Granick S (1954) Enzymatic conversion of delta-amino levulinic acid to porphobilinogen. Science 120(3131):1105–1106PubMedCrossRefPubMedCentralGoogle Scholar
  43. Granick S, Mauzerall D (1958) Pbrphyrin biosynthesis in erythrocytes. II. Enzymes converting gamma-aminolevulinic acid to coproporphyrinogen. J Biol Chem 232(2):1119–1140PubMedPubMedCentralGoogle Scholar
  44. Grimm B, Smith MA, von Wettstein D (1992) The role of Lys272 in the pyridoxal 5-phosphate active site of Synechococcus glutamate-1-semialdehyde aminotransferase. Eur J Biochem 206(2):579–585PubMedCrossRefPubMedCentralGoogle Scholar
  45. Han J, Zhou Z, Bu X, Zhu S, Zhang H, Sun H, Yang B (2013) Employing aqueous CdTe quantum dots with diversified surface functionalities to discriminate between heme (Fe(II)) and hemin (Fe(III)). Analyst 138(12):3402–3408PubMedCrossRefPubMedCentralGoogle Scholar
  46. Hansson M, Hederstedt L (1994) Bacillus subtilis HemY is a peripheral membrane protein essential for protoheme IX synthesis which can oxidize coproporphyrinogen III and protoporphyrinogen IX. J Bacteriol 176(19):5962–5970PubMedPubMedCentralCrossRefGoogle Scholar
  47. Hansson M, Gustafsson MC, Kannangara CG, Hederstedt L (1997a) Isolated Bacillus subtilis HemY has coproporphyrinogen III to coproporphyrin III oxidase activity. Biochim Biophys Acta 1340(1):97–104PubMedCrossRefPubMedCentralGoogle Scholar
  48. Hansson M, Gustafsson MC, Kannangara CG, Hederstedt L, Hansson M, Hederstedt L, Hansson M, Hederstedt L (1997b) Isolated Bacillus subtilis HemY has coproporphyrinogen III to coproporphyrin III oxidase activity. Bacillus subtilis HemY is a peripheral membrane protein essential for protoheme IX synthesis which can oxidize coproporphyrinogen III and protoporphyrinogen IX. Cloning and characterization of the Bacillus subtilis hemEHY gene cluster, which encodes protoheme IX biosynthetic enzymes. Biochim Biophys Acta 1340(1):97–104PubMedCrossRefPubMedCentralGoogle Scholar
  49. Hansson MD, Karlberg T, Rahardja MA, Al-Karadaghi S, Hansson M (2007) Amino acid residues His183 and Glu264 in Bacillus subtilis ferrochelatase direct and facilitate the insertion of metal ion into protoporphyrin IX. Biochemistry 46(1):87–94PubMedCrossRefGoogle Scholar
  50. Hart GJ, Miller AD, Leeper FJ, Battersby AR (1987) Biosynthesis of the natural porphyrins: proof that hydroxymethylbilane synthase (porphobilinogen deaminase) uses a novel binding group in its catalytic action. J Chem Soc Chem Commun 0:1762–1765CrossRefGoogle Scholar
  51. Haskamp V, Karrie S, Mingers T, Barthels S, Alberge F, Magalon A, Muller K, Bill E, Lubitz W, Kleeberg K et al (2018) The radical SAM protein HemW is a heme chaperone. J Biol Chem 293(7):2558–2572PubMedCrossRefGoogle Scholar
  52. Hawker CJ, Spivey AC, Leeper FJ, Battersby AR (1998) The rearrangement of 2H-pyrroles (pyrrolenines) related to the proposed spiro-intermediate for porphyrin biosynthesis. J Chem Soc Perkin Trans 1:1509–1518. (Biosynthesis of porphyrins and related macrocycles. Part 48)CrossRefGoogle Scholar
  53. Heinemann, I. U., N. Diekmann, A. Masoumi, M. Koch, A. Messerschmidt, M. Jahn, and D. Jahn. 2007. Functional definition of the tobacco protoporphyrinogen IX oxidase substrate-binding site. Biochem J 402 (3):575–80PubMedPubMedCentralCrossRefGoogle Scholar
  54. Heinemann IU, Jahn M, Jahn D (2008) The biochemistry of heme biosynthesis. Arch Biochem Biophys 474(2):238–251PubMedCrossRefGoogle Scholar
  55. Hennig M, Grimm B, Contestabile R, John RA, Jansonius JN (1997) Crystal structure of glutamate-1-semialdehyde aminomutase: an alpha2-dimeric vitamin B6-dependent enzyme with asymmetry in structure and active site reactivity. Proc Natl Acad Sci USA 94(10):4866–4871PubMedCrossRefGoogle Scholar
  56. Hoare DS, Heath H (1958) Intermediates in the biosynthesis of porphyrins from porphobilinogen by Rhodopseudomonas spheroides. Nature 181(4623):1592–1593PubMedCrossRefGoogle Scholar
  57. Hobbs C, Dailey HA, Shepherd M (2016) The HemQ coprohaem decarboxylase generates reactive oxygen species: implications for the evolution of classical haem biosynthesis. Biochem J 473(21):3997–4009PubMedPubMedCentralCrossRefGoogle Scholar
  58. Hobbs C, Reid JD, Shepherd M (2017) The coproporphyrin ferrochelatase of Staphylococcus aureus: mechanistic insights into a regulatory iron-binding site. Biochem J 474(20):3513–3522PubMedPubMedCentralCrossRefGoogle Scholar
  59. Hofbauer S, Gruber C, Pirker KF, Sundermann A, Schaffner I, Jakopitsch C, Oostenbrink C, Furtmuller PG, Obinger C (2014) Transiently produced hypochlorite is responsible for the irreversible inhibition of chlorite dismutase. Biochemistry 53(19):3145–3157PubMedPubMedCentralCrossRefGoogle Scholar
  60. Hofbauer S, Dalla Sega M, Scheiblbrandner S, Jandova Z, Schaffner I, Mlynek G, Djinovic-Carugo K, Battistuzzi G, Furtmuller PG, Oostenbrink C et al (2016) Chemistry and molecular dynamics simulations of heme b-HemQ and coproheme-HemQ. Biochemistry 55(38):5398–5412PubMedPubMedCentralCrossRefGoogle Scholar
  61. Ilag LL, Jahn D (1992) Activity and spectroscopic properties of the Escherichia coli glutamate 1-semialdehyde aminotransferase and the putative active site mutant K265R. Biochemistry 31(31):7143–7151PubMedCrossRefGoogle Scholar
  62. Ishida T, Yu L, Akutsu H, Ozawa K, Kawanishi S, Seto A, Inubushi T, Sano S (1998) A primitive pathway of porphyrin biosynthesis and enzymology in Desulfovibrio vulgaris. Proc Natl Acad Sci USA 95(9):4853–4858PubMedCrossRefGoogle Scholar
  63. Ishihara T, Tomita H, Hasegawa Y, Tsukagoshi N, Yamagata H, Udaka S (1995) Cloning and characterization of the gene for a protein thiol-disulfide oxidoreductase in Bacillus brevis. J Bacteriol 177(3):745–749PubMedPubMedCentralCrossRefGoogle Scholar
  64. Jackson AH, Sancovich HA, Ferramola AM, Evans N, Games DE, Matlin SA, Elder GH, Smith SG (1976) Macrocyclic intermediates in the biosynthesis of porphyrins. Philos Trans R Soc Lond Ser B Biol Sci 273(924):191–206CrossRefGoogle Scholar
  65. 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):540–546PubMedCrossRefGoogle Scholar
  66. Jacobs NJ, Jacobs JM, Brent P (1970) Formation of protoporphyrin from coproporphyrinogen in extracts of various bacteria. J Bacteriol 102(2):398–403PubMedPubMedCentralGoogle Scholar
  67. Jacobs NJ, Jacobs JM, Brent P (1971) Characterization of the late steps of microbial heme synthesis: conversion of coproporphyrinogen to protoporphyrin. J Bacteriol 107(1):203–209PubMedPubMedCentralGoogle Scholar
  68. Jaffe EK (2004) The porphobilinogen synthase catalyzed reaction mechanism. Bioorg Chem 32(5):316–325PubMedCrossRefGoogle Scholar
  69. Jaffe EK (2016) The remarkable character of porphobilinogen synthase. Acc Chem Res 49(11):2509–2517PubMedPubMedCentralCrossRefGoogle Scholar
  70. Jaffe EK, Lawrence SH (2012) Allostery and the dynamic oligomerization of porphobilinogen synthase. Arch Biochem Biophys 519(2):144–153PubMedCrossRefGoogle Scholar
  71. Jaffe EK, Volin M, Bronson-Mullins CR, Dunbrack RL Jr, Kervinen J, Martins J, Quinlan JF Jr, Sazinsky MH, Steinhouse EM, Yeung AT (2000) An artificial gene for human porphobilinogen synthase allows comparison of an allelic variation implicated in susceptibility to lead poisoning. J Biol Chem 275(4):2619–2626PubMedCrossRefGoogle Scholar
  72. Jahn D (1992) Expression of the Chlamydomonas reinhardtii chloroplast tRNA(Glu) gene in a homologous in vitro transcription system is independent of upstream promoter elements. Arch Biochem Biophys 298(2):505–513PubMedCrossRefGoogle Scholar
  73. Jahn M, Jahn D (2012) Tetrapyrroles. In: Michal G, Schomburg D (eds) Biochemical pathways: an atlas of biochemistry and molecular biology. Wiley, pp 82–92Google Scholar
  74. Jahn D, Verkamp E, Soll D (1992) Glutamyl-transfer RNA: a precursor of heme and chlorophyll biosynthesis. Trends Biochem Sci 17(6):215–218PubMedCrossRefGoogle Scholar
  75. Jordan PM, Seehra JS (1979) The biosynthesis of uroporphyrinogen III: order of assembly of the four porphobilinogen molecules in the formation of the tetrapyrrole ring. FEBS Lett 104(2):364–366PubMedCrossRefGoogle Scholar
  76. Jordan PM, Thomas SD, Warren MJ (1988) Purification, crystallization and properties of porphobilinogen deaminase from a recombinant strain of Escherichia coli K12. Biochem J 254(2):427–435PubMedPubMedCentralCrossRefGoogle Scholar
  77. Karlberg T, Lecerof D, Gora M, Silvegren G, Labbe-Bois R, Hansson M, Al-Karadaghi S (2002) Metal binding to Saccharomyces cerevisiae ferrochelatase. Biochemistry 41(46):13499–13506PubMedCrossRefGoogle Scholar
  78. Kato K, Tanaka R, Sano S, Tanaka A, Hosaka H (2010) Identification of a gene essential for protoporphyrinogen IX oxidase activity in the cyanobacterium Synechocystis sp. PCC6803. Proc Natl Acad Sci USA 107:16649–16654PubMedCrossRefGoogle Scholar
  79. Kaufholz AL, Hunter GA, Ferreira GC, Lendrihas T, Hering V, Layer G, Jahn M, Jahn D (2013a) Aminolaevulinic acid synthase of Rhodobacter capsulatus: high-resolution kinetic investigation of the structural basis for substrate binding and catalysis. Biochem J 451(2):205–216PubMedCrossRefGoogle Scholar
  80. Kaufholz AL, Layer G, Heinz DW, Jahn M, Jahn D (2013b) The structural basis of porphyrias-defects of heme biosynthetic enzymes. In: Ferreira GC, Kadish KM, Smith KM (eds) Handbook of porphyrin science. World Scientific, Singapore, pp 1–42Google Scholar
  81. Kikuchi G, Shemin D, Bachmann BJ (1958) The enzymic synthesis of delta-aminolevulinic acid. Biochim Biophys Acta 28(1):219–220PubMedCrossRefGoogle Scholar
  82. Koch M, Breithaupt C, Kiefersauer R, Freigang J, Huber R, Messerschmidt A (2004) Crystal structure of protoporphyrinogen IX oxidase: a key enzyme in haem and chlorophyll biosynthesis. EMBO J 23(8):1720–1728PubMedPubMedCentralCrossRefGoogle Scholar
  83. Kosugi N, Araki T, Fujita J, Tanaka S, Fujiwara T (2017) Growth phenotype analysis of heme synthetic enzymes in a halophilic archaeon, Haloferax volcanii. PLoS One 12(12):e0189913PubMedPubMedCentralCrossRefGoogle Scholar
  84. Kuhner M, Haufschildt K, Neumann A, Storbeck S, Streif J, Layer G (2014) The alternative route to heme in the methanogenic archaeon Methanosarcina barkeri. Archaea 2014:327637PubMedPubMedCentralCrossRefGoogle Scholar
  85. Kuhner M, Schweyen P, Hoffmann M, Ramos JV, Reijerse EJ, Lubitz W, Broering M, Layer G (2016) The auxiliary [4Fe-4S] cluster of the radical SAM heme synthase from Methanosarcina barkeri is involved in electron transfer. Chem Sci 7:4633–4643PubMedPubMedCentralCrossRefGoogle Scholar
  86. Lash TD (2005) The enigma of coproporphyrinogen oxidase: how does this unusual enzyme carry out oxidative decarboxylations to afford vinyl groups? Bioorg Med Chem Lett 15(20):4506–4509PubMedCrossRefGoogle Scholar
  87. Layer G, Verfurth K, Mahlitz E, Jahn D (2002) Oxygen-independent coproporphyrinogen-III oxidase HemN from Escherichia coli. J Biol Chem 277(37):34136–34142PubMedCrossRefGoogle Scholar
  88. 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):6214–6224PubMedPubMedCentralCrossRefGoogle Scholar
  89. Layer G, Heinz DW, Jahn D, Schubert WD (2004) Structure and function of radical SAM enzymes. Curr Opin Chem Biol 8(5):468–476PubMedCrossRefPubMedCentralGoogle Scholar
  90. Layer G, Kervio E, Morlock G, Heinz DW, Jahn D, Retey J, Schubert WD (2005) Structural and functional comparison of HemN to other radical SAM enzymes. Biol Chem 386(10):971–980PubMedCrossRefPubMedCentralGoogle Scholar
  91. Layer G, Pierik AJ, Trost M, Rigby SE, Leech HK, Grage K, Breckau D, Astner I, Jansch L, Heathcote P et al (2006) The substrate radical of Escherichia coli oxygen-independent coproporphyrinogen III oxidase HemN. J Biol Chem 281(23):15727–15734PubMedCrossRefPubMedCentralGoogle Scholar
  92. Layer G, Reichelt J, Jahn D, Heinz DW (2010) Structure and function of enzymes in heme biosynthesis. Protein Sci 19(6):1137–1161PubMedPubMedCentralCrossRefGoogle Scholar
  93. Lecerof D, Fodje M, Hansson A, Hansson M, Al-Karadaghi S (2000) Structural and mechanistic basis of porphyrin metallation by ferrochelatase. J Mol Biol 297(1):221–232PubMedCrossRefPubMedCentralGoogle Scholar
  94. Lecerof D, Fodje MN, Alvarez Leon R, Olsson U, Hansson A, Sigfridsson E, Ryde U, Hansson M, Al-Karadaghi S (2003) Metal binding to Bacillus subtilis ferrochelatase and interaction between metal sites. J Biol Inorg Chem 8(4):452–458PubMedCrossRefPubMedCentralGoogle Scholar
  95. Lee DS, Flachsova E, Bodnarova M, Demeler B, Martasek P, Raman CS (2005) Structural basis of hereditary coproporphyria. Proc Natl Acad Sci USA 102(40):14232–14237PubMedCrossRefPubMedCentralGoogle Scholar
  96. Levin EY (1968) Uroporphyrinogen 3 cosynthetase in bovine erythropoietic porphyria. Science 161(3844):907–908PubMedCrossRefPubMedCentralGoogle Scholar
  97. Lewis CA Jr, Wolfenden R (2008) Uroporphyrinogen decarboxylation as a benchmark for the catalytic proficiency of enzymes. Proc Natl Acad Sci USA 105(45):17328–17333PubMedCrossRefPubMedCentralGoogle Scholar
  98. Li S, Lou X, Xu Y, Teng X, Che S, Liu R, Bartlam M (2018) Crystal structure of a glutamate-1-semialdehyde-aminomutase from Pseudomonas aeruginosa PAO1. Biochem Biophys Res Commun 500(3):804–809PubMedCrossRefPubMedCentralGoogle Scholar
  99. Lieb C, Siddiqui RA, Hippler B, Jahn D, Friedrich B (1998) The Alcaligenes eutrophus hemN gene encoding the oxygen-independent coproporphyrinogen III oxidase, is required for heme biosynthesis during anaerobic growth. Arch Microbiol 169(1):52–60PubMedCrossRefPubMedCentralGoogle Scholar
  100. Lobo SA, Brindley A, Warren MJ, Saraiva LM (2009) Functional characterization of the early steps of tetrapyrrole biosynthesis and modification in Desulfovibrio vulgaris Hildenborough. Biochem J 420(2):317–325PubMedCrossRefPubMedCentralGoogle Scholar
  101. Lobo SA, Lawrence AD, Romao CV, Warren MJ, Teixeira M, Saraiva LM (2014) Characterisation of Desulfovibrio vulgaris haem b synthase, a radical SAM family member. Biochim Biophys Acta 1844(7):1238–1247PubMedCrossRefPubMedCentralGoogle Scholar
  102. Lobo SA, Scott A, Videira MA, Winpenny D, Gardner M, Palmer MJ, Schroeder S, Lawrence AD, Parkinson T, Warren MJ et al (2015) Staphylococcus aureus haem biosynthesis: characterisation of the enzymes involved in final steps of the pathway. Mol Microbiol 97(3):472–487PubMedCrossRefPubMedCentralGoogle Scholar
  103. Lüer C, Schauer S, Möbius K, Schulze J, Schubert WD, Heinz DW, Jahn D, Moser J (2005) Complex formation between glutamyl-tRNA reductase and glutamate-1-semialdehyde 2,1-aminomutase in Escherichia coli during the initial reactions of porphyrin biosynthesis. J Biol Chem 280(19):18568–18572PubMedCrossRefPubMedCentralGoogle Scholar
  104. Lüer C, Schauer S, Virus S, Schubert WD, Heinz DW, Moser J, Jahn D (2007) Glutamate recognition and hydride transfer by Escherichia coli glutamyl-tRNA reductase. FEBS J 274(17):4609–4614PubMedCrossRefPubMedCentralGoogle Scholar
  105. Martins BM, Grimm B, Mock HP, Huber R, Messerschmidt A (2001) Crystal structure and substrate binding modeling of the uroporphyrinogen-III decarboxylase from Nicotiana tabacum. Implications for the catalytic mechanism. J Biol Chem 276(47):44108–44116PubMedCrossRefPubMedCentralGoogle Scholar
  106. Masoumi A, Heinemann IU, Rohde M, Koch M, Jahn M, Jahn D (2008) Complex formation between protoporphyrinogen IX oxidase and ferrochelatase during haem biosynthesis in Thermosynechococcus elongatus. Microbiology 154(Pt 12):3707–3714PubMedCrossRefPubMedCentralGoogle Scholar
  107. Mathews MA, Schubert HL, Whitby FG, Alexander KJ, Schadick K, Bergonia HA, Phillips JD, Hill CP (2001) Crystal structure of human uroporphyrinogen III synthase. EMBO J 20(21):5832–5839PubMedPubMedCentralCrossRefGoogle Scholar
  108. Mathewson JH, Corwin AH (1961) Biosynthesis of pyrrole pigments: a mechanism for porphobilinogen polymerization. J Am Chem Soc 83:135–137CrossRefGoogle Scholar
  109. Mauzerall D, Granick S (1958) Porphyrin biosynthesis in erythrocytes. III. Uroporphyrinogen and its decarboxylase. J Biol Chem 232(2):1141–1162PubMedPubMedCentralGoogle Scholar
  110. Medlock AE, Dailey TA, Ross TA, Dailey HA, Lanzilotta WN (2007) A pi-helix switch selective for porphyrin deprotonation and product release in human ferrochelatase. J Mol Biol 373(4):1006–1016PubMedPubMedCentralCrossRefGoogle Scholar
  111. Medlock AE, Carter M, Dailey TA, Dailey HA, Lanzilotta WN (2009) Product release rather than chelation determines metal specificity for ferrochelatase. J Mol Biol 393(2):308–319PubMedPubMedCentralCrossRefGoogle Scholar
  112. Möbius K, Arias-Cartin R, Breckau D, Hännig AL, Riedmann K, Biedendieck R, Schroder S, Becher D, Magalon A, Moser J et al (2010) Heme biosynthesis is coupled to electron transport chains for energy generation. Proc Natl Acad Sci USA 107(23):10436–10441PubMedCrossRefGoogle Scholar
  113. Moore SJ, Sowa ST, Schuchardt C, Deery E, Lawrence AD, Ramos JV, Billig S, Birkemeyer C, Chivers PT, Howard MJ et al (2017) Elucidation of the biosynthesis of the methane catalyst coenzyme F430. Nature 543(7643):78–82PubMedPubMedCentralCrossRefGoogle Scholar
  114. Moser J, Lorenz S, Hubschwerlen C, Rompf A, Jahn D (1999) Methanopyrus kandleri glutamyl-tRNA reductase. J Biol Chem 274(43):30679–30685PubMedCrossRefGoogle Scholar
  115. Moser J, Schubert WD, Beier V, Bringemeier I, Jahn D, Heinz DW (2001) V-shaped structure of glutamyl-tRNA reductase, the first enzyme of tRNA-dependent tetrapyrrole biosynthesis. EMBO J 20(23):6583–6590PubMedPubMedCentralCrossRefGoogle Scholar
  116. Nishimura K, Taketani S, Inokuchi H (1995) Cloning of a human cDNA for protoporphyrinogen oxidase by complementation in vivo of a hemG mutant of Escherichia coli. J Biol Chem 270(14):8076–8080PubMedCrossRefGoogle Scholar
  117. Olsson U, Billberg A, Sjovall S, Al-Karadaghi S, Hansson M (2002) In vivo and in vitro studies of Bacillus subtilis ferrochelatase mutants suggest substrate channeling in the heme biosynthesis pathway. J Bacteriol 184(14):4018–4024PubMedPubMedCentralCrossRefGoogle Scholar
  118. Palmer DJ, Schroeder S, Lawrence AD, Deery E, Lobo SA, Saraiva LM, McLean KJ, Munro AW, Ferguson SJ, Pickersgill RW et al (2014) The structure, function and properties of sirohaem decarboxylase–an enzyme with structural homology to a transcription factor family that is part of the alternative haem biosynthesis pathway. Mol Microbiol 93(2):247–261PubMedPubMedCentralCrossRefGoogle Scholar
  119. Peng S, Zhang H, Gao Y, Pan X, Cao P, Li M, Chang W (2011) Crystal structure of uroporphyrinogen III synthase from Pseudomonas syringae pv. tomato DC3000. Biochem Biophys Res Commun 408(4):576–581PubMedCrossRefGoogle Scholar
  120. Pfanzagl V, Holcik L, Maresch D, Gorgone G, Michlits H, Furtmuller PG, Hofbauer S (2018) Coproheme decarboxylases – phylogenetic prediction versus biochemical experiments. Arch Biochem Biophys 640:27–36PubMedPubMedCentralCrossRefGoogle Scholar
  121. Phillips JD, Whitby FG, Kushner JP, Hill CP (2003) Structural basis for tetrapyrrole coordination by uroporphyrinogen decarboxylase. EMBO J 22(23):6225–6233PubMedPubMedCentralCrossRefGoogle Scholar
  122. Phillips JD, Whitby FG, Warby CA, Labbe P, Yang C, Pflugrath JW, Ferrara JD, Robinson H, Kushner JP, Hill CP (2004) Crystal structure of the oxygen-dependent coproporphyrinogen oxidase (Hem13p) of Saccharomyces cerevisiae. J Biol Chem 279(37):38960–38968PubMedCrossRefGoogle Scholar
  123. Phillips JD, Warby CA, Whitby FG, Kushner JP, Hill CP (2009) Substrate shuttling between active sites of uroporphyrinogen decarboxylase is not required to generate coproporphyrinogen. J Mol Biol 389(2):306–314PubMedPubMedCentralCrossRefGoogle Scholar
  124. Pluta P, Roversi P, Bernardo-Seisdedos G, Rojas AL, Cooper JB, Gu S, Pickersgill RW, Millet O (2018) Structural basis of pyrrole polymerization in human porphobilinogen deaminase. Biochim Biophys Acta 1862:1948CrossRefGoogle Scholar
  125. Porra RJ, Falk JE (1961) Protein-bound porphyrins associated with protoporphyrin biosynthesis. Biochem Biophys Res Commun 5:179–184PubMedCrossRefGoogle Scholar
  126. Porra RJ, Falk JE (1964) The enzymic conversion of coproporphyrinogen 3 into protoporphyrin 9. Biochem J 90(1):69–75PubMedPubMedCentralCrossRefGoogle Scholar
  127. Qi M, Lorenz M, Vogelpohl A (2002) Mathematical solution of the two-dimensional dispersion model. Chem Eng Technol 25(7):693–697CrossRefGoogle Scholar
  128. Qin X, Sun L, Wen X, Yang X, Tan Y, Jin H, Cao Q, Zhou W, Xi Z, Shen Y (2010) Structural insight into unique properties of protoporphyrinogen oxidase from Bacillus subtilis. J Struct Biol 170:76–82PubMedCrossRefPubMedCentralGoogle Scholar
  129. Rand K, Noll C, Schiebel HM, Kemken D, Dulcks T, Kalesse M, Heinz DW, Layer G (2010) The oxygen-independent coproporphyrinogen III oxidase HemN utilizes harderoporphyrinogen as a reaction intermediate during conversion of coproporphyrinogen III to protoporphyrinogen IX. Biol Chem 391(1):55–63PubMedCrossRefGoogle Scholar
  130. Randau L, Schauer S, Ambrogelly A, Salazar JC, Moser J, Sekine S, Yokoyama S, Soll D, Jahn D (2004) tRNA recognition by glutamyl-tRNA reductase. J Biol Chem 279(33):34931–34937PubMedCrossRefGoogle Scholar
  131. Raux E, Leech HK, Beck R, Schubert HL, Santander PJ, Roessner CA, Scott AI, Martens JH, Jahn D, Thermes C et al (2003) Identification and functional analysis of enzymes required for precorrin-2 dehydrogenation and metal ion insertion in the biosynthesis of sirohaem and cobalamin in Bacillus megaterium. Biochem J 370(Pt 2):505–516PubMedPubMedCentralCrossRefGoogle Scholar
  132. Rehse PH, Kitao T, Tahirov TH (2005) Structure of a closed-form uroporphyrinogen-III C-methyltransferase from Thermus thermophilus. Acta Crystallogr D Biol Crystallogr 61(Pt 7):913–919PubMedCrossRefGoogle Scholar
  133. Roberts A, Gill R, Hussey RJ, Mikolajek H, Erskine PT, Cooper JB, Wood SP, Chrystal EJ, Shoolingin-Jordan PM (2013) Insights into the mechanism of pyrrole polymerization catalysed by porphobilinogen deaminase: high-resolution X-ray studies of the Arabidopsis thaliana enzyme. Acta Crystallogr D Biol Crystallogr 69(Pt 3):471–485PubMedCrossRefGoogle Scholar
  134. Sano S, Granick S (1961) Mitochondrial coproporphyrinogen oxidase and protoporphyrin formation. J Biol Chem 236:1173–1180PubMedGoogle Scholar
  135. Sasarman A, Letowski J, Czaika G, Ramirez V, Nead MA, Jacobs JM, Morais R (1993) Nucleotide sequence of the hemG gene involved in the protoporphyrinogen oxidase activity of Escherichia coli K12. Can J Microbiol 39(12):1155–1161PubMedCrossRefGoogle Scholar
  136. Schauer S, Chaturvedi S, Randau L, Moser J, Kitabatake M, Lorenz S, Verkamp E, Schubert WD, Nakayashiki T, Murai M et al (2002) Escherichia coli glutamyl-tRNA reductase. Trapping the thioester intermediate. J Biol Chem 277(50):48657–48663PubMedCrossRefGoogle Scholar
  137. Schubert HL, Raux E, Brindley AA, Leech HK, Wilson KS, Hill CP, Warren MJ (2002) The structure of Saccharomyces cerevisiae Met8p, a bifunctional dehydrogenase and ferrochelatase. EMBO J 21(9):2068–2075PubMedPubMedCentralCrossRefGoogle Scholar
  138. Schubert HL, Phillips JD, Heroux A, Hill CP (2008) Structure and mechanistic implications of a uroporphyrinogen III synthase-product complex. Biochemistry 47(33):8648–8655PubMedPubMedCentralCrossRefGoogle Scholar
  139. Schulze JO, Masoumi A, Nickel D, Jahn M, Jahn D, Schubert WD, Heinz DW (2006) Crystal structure of a non-discriminating glutamyl-tRNA synthetase. J Mol Biol 361(5):888–897PubMedCrossRefGoogle Scholar
  140. Seehra JS, Jordan PM, Akhtar M (1983) Anaerobic and aerobic coproporphyrinogen III oxidases of Rhodopseudomonas spheroides. Mechanism and stereochemistry of vinyl group formation. Biochem J 209(3):709–718PubMedPubMedCentralCrossRefGoogle Scholar
  141. Shemin D, Rittenberg D (1945) The utilization of glycine for the synthesis of a porphyrin. J Biol Chem 159:567–568Google Scholar
  142. Shepherd M, Dailey TA, Dailey HA (2006) A new class of [2Fe-2S]-cluster-containing protoporphyrin (IX) ferrochelatases. Biochem J 397(1):47–52PubMedPubMedCentralCrossRefGoogle Scholar
  143. Sigfridsson E, Ryde U (2003) The importance of porphyrin distortions for the ferrochelatase reaction. J Biol Inorg Chem 8(3):273–282PubMedCrossRefGoogle Scholar
  144. Silva PJ, Ramos MJ (2008) A comparative density-functional study of the reaction mechanism of the O2-dependent coproporphyrinogen III oxidase. Bioorg Med Chem 16(6):2726–2733PubMedCrossRefGoogle Scholar
  145. Silva PJ, Schulz C, Jahn D, Jahn M, Ramos MJ (2010) A tale of two acids: when arginine is a more appropriate acid than H3O+. J Phys Chem B 114:8994–9001PubMedCrossRefGoogle Scholar
  146. Skotnicova P, Sobotka R, Shepherd M, Hajek J, Hrouzek P, Tichy M (2018) The cyanobacterial protoporphyrinogen oxidase HemJ is a new b-type heme protein functionally coupled with coproporphyrinogen III oxidase. J Biol Chem 293:12394PubMedCrossRefGoogle Scholar
  147. Smith AD, Warren MJ, Refsum H (2018) Vitamin B12. Adv Food Nutr Res 83:215–279PubMedCrossRefGoogle Scholar
  148. Spencer P, Jordan PM (1995) Characterization of the two 5-aminolaevulinic acid binding sites, the A- and P-sites, of 5-aminolaevulinic acid dehydratase from Escherichia coli. Biochem J 305(Pt 1):151–158PubMedPubMedCentralCrossRefGoogle Scholar
  149. Spencer JB, Stolowich NJ, Roessner CA, Scott AI (1993) The Escherichia coli cysG gene encodes the multifunctional protein, siroheme synthase. FEBS Lett 335(1):57–60PubMedCrossRefGoogle Scholar
  150. Stark WM, Baker MG, Raithby PR, Leeper FJ, Battersby AR (1985) The spiro intermediate proposed for biosynthesis of the natural porphyrins: synthesis and properties of its macrocycle. J Chem Soc Chem Commun (19):1294–1296Google Scholar
  151. Stark WM, Hart GJ, Battersby AR (1986) Synthetic studies on the proposed spiro intermediate for biosynthesis of the natural porphyrins: inhibition of cosynthetase. J Chem Soc Chem Commun (6):465–467Google Scholar
  152. Stark MW, Hawker CJ, Hart GJ, Phillippides A, Petersen PM, Lewis DJ, Leeper FJ, Battersby AR (1993) Biosynthesis of porphyrins and related macrocycles. Part 40. Synthesis of a spiro-lactam related to the proposed spiro-intermediate for porphyrin biosynthesis: inhibition of cosynthetase. J Chem Soc Perkin Trans 1:2875–2892CrossRefGoogle Scholar
  153. Stephenson JR, Stacey JA, Morgenthaler JB, Friesen JA, Lash TD, Jones MA (2007) Role of aspartate 400, arginine 262, and arginine 401 in the catalytic mechanism of human coproporphyrinogen oxidase. Protein Sci 16(3):401–410PubMedPubMedCentralCrossRefGoogle Scholar
  154. Stevens E, Frydman B (1968) Isolation and properties of wheat germ uroporphyrinogen 3 cosynthetase. Biochim Biophys Acta 151(2):429–437PubMedCrossRefGoogle Scholar
  155. Stojanovski BM, Hunter GA, Jahn M, Jahn D, Ferreira GC (2014) Unstable reaction intermediates and hysteresis during the catalytic cycle of 5-aminolevulinate synthase: implications from using pseudo and alternate substrates and a promiscuous enzyme variant. J Biol Chem 289(33):22915–22925PubMedPubMedCentralCrossRefGoogle Scholar
  156. Storbeck S, Walther J, Muller J, Parmar V, Schiebel HM, Kemken D, Dulcks T, Warren MJ, Layer G (2009) The Pseudomonas aeruginosa nirE gene encodes the S-adenosyl-L-methionine-dependent uroporphyrinogen III methyltransferase required for heme d(1) biosynthesis. FEBS J 276(20):5973–5982PubMedCrossRefGoogle Scholar
  157. Storbeck S, Rolfes S, Raux-Deery E, Warren MJ, Jahn D, Layer G (2010) A novel pathway for the biosynthesis of heme in Archaea: genome-based bioinformatic predictions and experimental evidence. Archaea 2010:175050PubMedPubMedCentralCrossRefGoogle Scholar
  158. Storbeck S, Saha S, Krausze J, Klink BU, Heinz DW, Layer G (2011) Crystal structure of the heme d1 biosynthesis enzyme NirE in complex with its substrate reveals new insights into the catalytic mechanism of S-adenosyl-l-methionine-dependent uroporphyrinogen III methyltransferases. J Biol Chem 286(30):26754–26767PubMedPubMedCentralCrossRefGoogle Scholar
  159. Streit BR, Celis AI, Moraski GC, Shisler KA, Shepard EM, Rodgers KR, Lukat-Rodgers GS, DuBois JL (2018) Decarboxylation involving a ferryl, propionate, and a tyrosyl group in a radical relay yields heme b. J Biol Chem 293(11):3989–3999PubMedCrossRefPubMedCentralGoogle Scholar
  160. Strey J, Wittchen KD, Meinhardt F (1999) Regulation of beta-galactosidase expression in Bacillus megaterium DSM319 by a XylS/AraC-type transcriptional activator. J Bacteriol 181(10):3288–3292PubMedPubMedCentralGoogle Scholar
  161. Tait GH (1969) Coproporphyrinogenase activity in extracts from Rhodopseudomonas spheroides. Biochem Biophys Res Commun 37(1):116–122PubMedCrossRefGoogle Scholar
  162. Tait GH (1972) Coproporphyrinogenase activities in extracts of Rhodopseudomonas spheroides and Chromatium strain D. Biochem J 128(5):1159–1169PubMedPubMedCentralCrossRefGoogle Scholar
  163. Tan FC, Cheng Q, Saha K, Heinemann IU, Jahn M, Jahn D, Smith AG (2008) Identification and characterization of the Arabidopsis gene encoding the tetrapyrrole biosynthesis enzyme uroporphyrinogen III synthase. Biochem J 410(2):291–299PubMedCrossRefGoogle Scholar
  164. 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 177(11):3326–3331PubMedPubMedCentralCrossRefGoogle Scholar
  165. Uchida T, Funamizu T, Chen M, Tanaka Y, Ishimori K (2018) Heme binding to porphobilinogen deaminase from Vibrio cholerae decelerates the formation of 1-hydroxymethylbilane. ACS Chem Biol 13(3):750–760PubMedCrossRefGoogle Scholar
  166. Vevodova J, Graham RM, Raux E, Schubert HL, Roper DI, Brindley AA, Ian Scott A, Roessner CA, Stamford NP, Elizabeth Stroupe M et al (2004) Structure/function studies on a S-adenosyl-l-methionine-dependent uroporphyrinogen III C methyltransferase (SUMT), a key regulatory enzyme of tetrapyrrole biosynthesis. J Mol Biol 344(2):419–433PubMedCrossRefGoogle Scholar
  167. Wang P, Grimm B (2015) Organization of chlorophyll biosynthesis and insertion of chlorophyll into the chlorophyll-binding proteins in chloroplasts. Photosynth Res 126(2–3):189–202PubMedCrossRefGoogle Scholar
  168. Wang Y, Shen Y, Ryde U (2009) QM/MM study of the insertion of metal ion into protoporphyrin IX by ferrochelatase. J Inorg Biochem 103(12):1680–1686PubMedCrossRefGoogle Scholar
  169. Wang B, Wen X, Qin X, Wang Z, Tan Y, Shen Y, Xi Z (2013) Quantitative structural insight into human variegate porphyria disease. J Biol Chem 288:11731PubMedPubMedCentralCrossRefGoogle Scholar
  170. Warren MJ, Jordan PM (1988) Investigation into the nature of substrate binding to the dipyrromethane cofactor of Escherichia coli porphobilinogen deaminase. Biochemistry 27(25):9020–9030PubMedCrossRefGoogle Scholar
  171. Warren MJ, Roessner CA, Santander PJ, Scott AI (1990) The Escherichia coli cysG gene encodes S-adenosylmethionine-dependent uroporphyrinogen III methylase. Biochem J 265(3):725–729PubMedPubMedCentralCrossRefGoogle Scholar
  172. Whitby FG, Phillips JD, Kushner JP, Hill CP (1998) Crystal structure of human uroporphyrinogen decarboxylase. EMBO J 17(9):2463–2471PubMedPubMedCentralCrossRefGoogle Scholar
  173. Woodcock SC, Jordan PM (1994) Evidence for participation of aspartate-84 as a catalytic group at the active site of porphobilinogen deaminase obtained by site-directed mutagenesis of the hemC gene from Escherichia coli. Biochemistry 33(9):2688–2695PubMedCrossRefGoogle Scholar
  174. Xu K, Elliott T (1994) Cloning, DNA sequence, and complementation analysis of the Salmonella typhimurium hemN gene encoding a putative oxygen-independent coproporphyrinogen III oxidase. J Bacteriol 176(11):3196–3203PubMedPubMedCentralCrossRefGoogle Scholar
  175. Zhao A, Fang Y, Chen X, Zhao S, Dong W, Lin Y, Gong W, Liu L (2014) Crystal structure of Arabidopsis glutamyl-tRNA reductase in complex with its stimulator protein. Proc Natl Acad Sci USA 111(18):6630–6635PubMedCrossRefGoogle Scholar
  176. Zheng K, Ngo PD, Owens VL, Yang XP, Mansoorabadi SO (2016) The biosynthetic pathway of coenzyme F430 in methanogenic and methanotrophic archaea. Science 354(6310):339–342CrossRefGoogle Scholar
  177. Zwerschke D, Karrie S, Jahn D, Jahn M (2014) Leishmania major possesses a unique HemG-type protoporphyrinogen IX oxidase. Biosci Rep 34(4):e00124daileyCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Katrin Müller
    • 1
  • Toni Mingers
    • 1
  • V. Haskamp
    • 1
  • Dieter Jahn
    • 2
  • Martina Jahn
    • 1
    Email author
  1. 1.Institute of MicrobiologyBraunschweig University of TechnologyBraunschweigGermany
  2. 2.Institute of Microbiology, Braunschweig University of Technology, Braunschweig Integrated Center of Systems Biology BRICSBraunschweigGermany

Personalised recommendations