title: Molecular phylogeny and intricate evolutionary history of the three isofunctional enzymes involved in the oxidation of protoporphyrinogen IX.
abstract: Tetrapyrroles such as heme and chlorophyll are essential for biological processes, including oxygenation, respiration, and photosynthesis. In the tetrapyrrole biosynthesis pathway, protoporphyrinogen IX oxidase (Protox) catalyzes the formation of protoporphyrin IX, the last common intermediate for the biosynthesis of heme and chlorophyll. Three nonhomologous isofunctional enzymes, HemG, HemJ, and HemY, for Protox have been identified. To reveal the distribution and evolution of the three Protox enzymes, we identified homologs of each along with other heme biosynthetic enzymes by whole-genome clustering across three domains of life. Most organisms possess only one of the three Protox types, with some exceptions. Detailed phylogenetic analysis revealed that HemG is mostly limited to γ-Proteobacteria whereas HemJ may have originated within α-Proteobacteria and transferred to other Proteobacteria and Cyanobacteria. In contrast, HemY is ubiquitous in prokaryotes and is the only Protox in eukaryotes, so this type may be the ancestral Protox. Land plants have a unique HemY homolog that is also shared by Chloroflexus species, in addition to the main HemY homolog originating from Cyanobacteria. Meanwhile, organisms missing any Protox can be classified into two groups; those lacking most heme synthetic genes, which necessarily depend on external heme supply, and those lacking only genes involved in the conversion of uroporphyrinogen III into heme, which would use a precorrin2-dependent alternative pathway. However, hemN encoding coproporphyrinogen IX oxidase was frequently found in organisms lacking Protox enzyme, which suggests a unique role of this gene other than in heme biosynthesis.
authors.affiliation: Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Japan kkobayashi@bio.c.u-tokyo.ac.jp naokisat@bio.c.u-tokyo.ac.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of General Systems Studies, Graduate School of Arts and Sciences, The University of Tokyo, Japan.
authors.forename: Tatsuru
authors.initials: T
authors.lastname: Masuda
authors.affiliation: Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tajima
authors.affiliation: Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Japan CREST, JST, Saitama, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Wada
authors.affiliation: Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Japan CREST, JST, Saitama, Japan kkobayashi@bio.c.u-tokyo.ac.jp naokisat@bio.c.u-tokyo.ac.jp.
authors.forename: Naoki
authors.initials: N
authors.lastname: Sato
mesh_terms: D000818:Animals; D001419:Bacteria / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D053898:Biosynthetic Pathways; D006418:Heme / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010802:Phylogeny; D010944:Plants / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D050768:Protoporphyrinogen Oxidase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011524:Protoporphyrins / Q000235:genetics / Q000378:metabolism*; D045725:Tetrapyrroles / Q000235:genetics / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D011524:Protoporphyrins; D045725:Tetrapyrroles; D006418:Heme; C011539:protoporphyrinogen; D050768:Protoporphyrinogen Oxidase
keywords: HemG; HemJ; HemY; heme; protoporphyrin IX; tetrapyrrole
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