Enzymatic Preparation of Tetrapyrrole Intermediates

  • Martin J. Warren
  • Peter M. Shoolingin-Jordan


Tetrapyrroles are intensely colored natural products of vital importance in the biosphere for essential processes such as respiration and photosynthesis and are also of key importance as cofactors in a number of other enzyme reactions. Tetrapyrroles may either be linear in nature, as found in the bilins, or cyclic as in the hemes, chlorophylls, and corrins. In the cyclic tetrapyrrole group, the four centrally located pyrrole nitrogen atoms of the macrocyclic ring offer a range of possibilities for metal chelation. Modulation of the properties of the metal-lotetrapyrrole prosthetic groups by individual proteins give rise to a remarkably versatile family of powerful bio-organic reagents.


Ammonium Sulfate Incubation Mixture Solid Ammonium Sulfate Subunit Molecular Mass Sodium Amalgam 
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  1. 1.
    Akhtar, M. and C. Jones. 1986. Preparation of stereospecifically labelled porphobilinogens. Methods Enzymol. 723:375–383.CrossRefGoogle Scholar
  2. 2.
    Al-Karadaghi, S., M. Hansson, S. Nikonov, B. Jonsson, and L. Hederstedt. 1997. Crystal structure of ferrochelatase: the terminal enzyme in heme biosynthesis. Structure 5:1501–1510.PubMedCrossRefGoogle Scholar
  3. 3.
    Blanche, R, L. Debussche, D. Thibaut, J. Crouzet, and B. Cameron. 1989. Purification and characterization of S-adenosyl-L-methionine:uroporphyrinogen methyltransferase from Pseudomonas denitrificans. J. Bacteriol. 171:4222–4231.PubMedGoogle Scholar
  4. 4.
    Bolt, E.L., L. Kryszak, J. Zeilstra-Ryalls, P.M. Shoolingin-Jordan, and M.J. Warren. 1999. Characterisation of the R. sphaeroides 5-aminolevulinic acid synthase isoenzymes, HemA and HemT, isolated from recombinant Escherichia coli. Eur. J. Biochem. 265:1–11.CrossRefGoogle Scholar
  5. 5.
    Dailey, H.A. 1977. Purification and characterisation of the membrane bound ferrochelatase from Spirillum itersonii. J. Bacteriol. 732:302–307.Google Scholar
  6. 6.
    Dailey, HA and T.A. Dailey. 1996. Protoporphyrinogen oxidase of Myxococcus xanthus. J. Biol. Chem. 277:8714–8718.CrossRefGoogle Scholar
  7. 7.
    Erskine, P.T., N. Senior, S. Awan, R. Lambert, G. Lewis, I.J. Tickle, M. Sarwar, P. Spencer, P. Thomas, M.J. Warren et al. 1997. X-ray structure of 5-amino-laevulinic acid dehydratase, a hybrid aldolase. Nat. Struct. Biol. 4:1025–1031.PubMedCrossRefGoogle Scholar
  8. 8.
    Erskine, P.T., E. Norton, J.B. Cooper, R. Lambert, A. Coker, G. Lewis, P. Spencer, M. Sarwar, S.P. Wood, M.J. Warren, and P.M. Shoolingin-Jordan. 1999. X-Ray structure of 5-aminolevulinic acid dehydratase from Escherichia coli complexed with the inhibitor levulinic acid at 2.0 A resolution. Biochemistry 38:4266–4276.PubMedCrossRefGoogle Scholar
  9. 9.
    Ferreira, G.C. and J. Gong. 1995. 5-Aminolaevulinate synthase and the first step of heme biosynthesis. J. Bioenerg. Biomembr. 27:151–159.PubMedCrossRefGoogle Scholar
  10. 10.
    Guo, G.G., M. Gu, and J.D. Etlinger. 1994. 240-kDa proteasome inhibitor CF-2. is identical to delta-aminolevulinic acid dehydratase. J. Biol. Chem. 269:12399–12402.PubMedGoogle Scholar
  11. 11.
    Hansson, M. and L. Hederstedt. 1994. Purification and characterisation of a water-soluble ferrochelatase from Bacillus subtilis. Eur. J. Biochem. 220:201–208.PubMedCrossRefGoogle Scholar
  12. 12.
    Hunter, G.A. and G.C. Ferreira. 1995. A continuous spectrophotometric assay for 5-aminolevulinate synthase that utilizes substrate cycling. Anal. Biochem. 226:221–224.PubMedCrossRefGoogle Scholar
  13. 13.
    Jaffe, E.K. 1995. Porphobilinogen synthase, the first source of heme’s asymmetry. J. Bioenerg. Biomembr. 27:169–179.PubMedCrossRefGoogle Scholar
  14. 14.
    Jaffe, E.K. 2000. The porphobilinogen synthase family of metalloenzymes. Acta Crystallogr. D 56:115–128.PubMedCrossRefGoogle Scholar
  15. 15.
    Jordan, P.M., G. Burton, H. Nordlüv, M.M. Schneider, L. Pryde, and A.I. Scott. 1979. J. Chem. Soc., Chem. Commun. 204–205.Google Scholar
  16. 16.
    Jordan, P.M. and M.J. Warren. 1987. Evidence for a dipyrromethane cofactor at the catalytic site of E. coli porphobilinogen deaminase. FEBS Lett. 225:87–92.PubMedCrossRefGoogle Scholar
  17. 17.
    Jordan, PM. 1991. The biosynthesis of 5-aminolaevulinic acid and its transformation into uroporphyrinogen III, p. 1–66. In A. Neuberger and L.L.M. van Deenen (Eds.), and P.M. Jordan (Vol. Ed.), New Comprehensive Biochemistry, Vol. 19, Biosynthesis of Tetrapyrroles. Elsevier, Amsterdam.Google Scholar
  18. 18.
    Kannangara, C.G., R.V. Andersen, B. Pontoppidan, R. Willows, and D. von Wettstein. 1994. Enzymic and mechanistic studies on the conversion of glutamate to 5-aminolaevulinate, p. 3–25. In D.J. Chadwick, and K. Ackrill (Eds.), The Biosynthesis of Tetrapyrrole Pigments, Ciba Foundation Symposium 180. John Wiley & Sons, New York.Google Scholar
  19. 19.
    Kappas, A., S. Sassa, R.A. Galbraith, and Y. Nordmann. 1995. The porphyrias, p. 2103–2160. In C.R. Scriver, A.L. Beaudet, W.S. Sly, and D. Valle (Eds.), The Metabolic and Molecular Basis of Inherited Disease, 7th ed. McGraw Hill, New York.Google Scholar
  20. 20.
    Li, J.M., C.S. Russell, and S.D. Cosloy. 1989. The structure of the E. coli hemB gene. Gene 75:177–184.PubMedCrossRefGoogle Scholar
  21. 21.
    Mauzerall, D. and S. Granick. 1956. The occurrence and determination of ·-aminolevulinic acid and porphobilinogen in urine. J. Biol. Chem. 219:435–446.PubMedGoogle Scholar
  22. 22.
    Medlock, A.E. and HA. Dailey. 1996. Human protoporphyrinogen oxidase is not a metalloprotein. J. Biol. Chem. 271:32507–32510.PubMedCrossRefGoogle Scholar
  23. 23.
    Neidle, E.L. and S. Kaplan. 1993. Expression of Rhodobacter sphaeroides hemA and hem T genes encoding two 5-aminolaevulinic acid synthase isoenzymes. J. Bacteriol. 175:2292–2303.PubMedGoogle Scholar
  24. 24.
    Phillips, J., EG. Whitby, J.P. Kushner, and C.P. Hill. 1997. Characterisation and crystallization of human uroporphyrinogen decarboxylase. Prot. Sci. 6:1343–1346.CrossRefGoogle Scholar
  25. 25.
    Raux, E., T. McVeigh, S.E. Peters, T. Leustek, and M.J. Warren. 1999. The role of Saccharomyces cerevisiae Metlp and Met8p in siroheme and cobalamin biosynthesis. Biochem. J. 338:701–708.PubMedCrossRefGoogle Scholar
  26. 26.
    Scopes, R.K. 1987. Protein Purification, Principles and Practice, 2nd ed. Springer Verlag, Basel.Google Scholar
  27. 27.
    Shoolingin-Jordan, P.M., J.E. LeLean, and A.J. Lloyd. 1997. Continuous coupled assay for 5-aminolevulinate synthase. Methods Enzymol. 281:309–316.PubMedCrossRefGoogle Scholar
  28. 28.
    Shoolingin-Jordan, P.M. and K.-M. Cheung. 1999. Biosynthesis of heme, p. 61–107. In D.H.R. Barton, K. Nakanishi, and O. Meth-Cohn (Eds.), and J.W. Kelly (Vol. Ed.), Comprehensive Natural Products Chemistry, Vol. 4, Amino Acids, Peptides, Porphyrins and Alkaloids. Elsevier, Amsterdam.Google Scholar
  29. 29.
    Smith, A.G. and W.T. Griffiths. 1993. Enzymes of chlorophyll and heme biosynthesis. Methods Plant Biochem. 9:299–343.Google Scholar
  30. 30.
    Spencer, J.B., N.J. Stolowich, C.A. Roessner, and A.I. Scott. 1993. The Escherichia coli cysG gene encodes the multifunctional protein, siroheme synthase. FEBS Lett. 335:57–60.PubMedCrossRefGoogle Scholar
  31. 31.
    Spencer, P. and P.M. Jordan. 1993. Purification and characterisation of 5-aminolaevulinic acid dehydratase from E. coli and a study of reactive thiols at the metal binding domain. Biochem. J. 290:279–287.PubMedGoogle Scholar
  32. 32.
    Thomas, S.D. and P.M. Jordan. 1986. Nucleotide sequence of the hemC locus encoding porphobilinogen deaminase of Escherichia coli K12. Nucleic Acids Res. 14:6215–6226.PubMedCrossRefGoogle Scholar
  33. 33.
    Whitby, EG., J.D. Phillips, J.P. Kushner, and C.P. Hill. 1998. Crystal structure of human uroporphyrinogen decarboxylase. EMBO J. 17:2463–2471.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press, Totowa, NJ 2002

Authors and Affiliations

  • Martin J. Warren
    • 1
  • Peter M. Shoolingin-Jordan
    • 2
  1. 1.School of Biological SciencesQueen Mary Westfield CollegeLondonEngland, UK
  2. 2.School of Biological SciencesUniversity of SouthamptonSouthamptonEngland, UK

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