title: A novel pathway for the biosynthesis of heme in Archaea: genome-based bioinformatic predictions and experimental evidence.
abstract: Heme is an essential prosthetic group for many proteins involved in fundamental biological processes in all three domains of life. In Eukaryota and Bacteria heme is formed via a conserved and well-studied biosynthetic pathway. Surprisingly, in Archaea heme biosynthesis proceeds via an alternative route which is poorly understood. In order to formulate a working hypothesis for this novel pathway, we searched 59 completely sequenced archaeal genomes for the presence of gene clusters consisting of established heme biosynthetic genes and colocalized conserved candidate genes. Within the majority of archaeal genomes it was possible to identify such heme biosynthesis gene clusters. From this analysis we have been able to identify several novel heme biosynthesis genes that are restricted to archaea. Intriguingly, several of the encoded proteins display similarity to enzymes involved in heme d(1) biosynthesis. To initiate an experimental verification of our proposals two Methanosarcina barkeri proteins predicted to catalyze the initial steps of archaeal heme biosynthesis were recombinantly produced, purified, and their predicted enzymatic functions verified.
authors.affiliation: Institute for Microbiology, Technical University of Braunschweig, Spielmannstraße 7, 38106 Braunschweig, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Storbeck
authors.forename: Sarah
authors.initials: S
authors.lastname: Rolfes
authors.forename: Evelyne
authors.initials: E
authors.lastname: Raux-Deery
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Warren
authors.forename: Dieter
authors.initials: D
authors.lastname: Jahn
authors.forename: Gunhild
authors.initials: G
authors.lastname: Layer
mesh_terms: D001105:Archaea / Q000235:genetics* / Q000378:metabolism*; D019843:Archaeal Proteins / Q000235:genetics / Q000378:metabolism; D001419:Bacteria / Q000235:genetics; D053898:Biosynthetic Pathways / Q000235:genetics*; D003001:Cloning, Molecular; D019295:Computational Biology / Q000379:methods; D056890:Eukaryota / Q000235:genetics; D019766:Genes, Archaeal; D006418:Heme / Q000096:biosynthesis*; D017021:Methanosarcina barkeri / Q000201:enzymology; D008954:Models, Biological; D005810:Multigene Family; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D019843:Archaeal Proteins; D011994:Recombinant Proteins; D006418:Heme