Recent advances in the biosynthesis of modified tetrapyrroles: The discovery of an alternative pathway for the formation of heme and heme d 1

Shilpa Bali, David J. Palmer, Susanne Schroeder, Stuart J. Ferguson, Martin J. Warren

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40 Citations (Scopus)


Hemes (a, b, c, and o) and heme d 1 belong to the group of modified tetrapyrroles, which also includes chlorophylls, cobalamins, coenzyme F430, and siroheme. These compounds are found throughout all domains of life and are involved in a variety of essential biological processes ranging from photosynthesis to methanogenesis. The biosynthesis of heme b has been well studied in many organisms, but in sulfate-reducing bacteria and archaea, the pathway has remained a mystery, as many of the enzymes involved in these characterized steps are absent. The heme pathway in most organisms proceeds from the cyclic precursor of all modified tetrapyrroles uroporphyrinogen III, to coproporphyrinogen III, which is followed by oxidation of the ring and finally iron insertion. Sulfate-reducing bacteria and some archaea lack the genetic information necessary to convert uroporphyrinogen III to heme along the "classical" route and instead use an "alternative" pathway. Biosynthesis of the isobacteriochlorin heme d1, a cofactor of the dissimilatory nitrite reductase cytochrome cd1, has also been a subject of much research, although the biosynthetic pathway and its intermediates have evaded discovery for quite some time. This review focuses on the recent advances in the understanding of these two pathways and their surprisingly close relationship via the unlikely intermediate siroheme, which is also a cofactor of sulfite and nitrite reductases in many organisms. The evolutionary questions raised by this discovery will also be discussed along with the potential regulation required by organisms with overlapping tetrapyrrole biosynthesis pathways.

Original languageEnglish
Pages (from-to)2837-2863
Number of pages27
JournalCellular and Molecular Life Sciences
Issue number15
Publication statusPublished - Aug 2014


  • Alternative heme biosynthesis
  • Heme
  • Modified tetrapyrrole
  • Siroheme
  • Tetrapyrrole biosynthesis

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