Molecular hijacking of siroheme for the synthesis of heme and d1 heme.

Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom.
Proceedings of the National Academy of Sciences (Impact Factor: 9.74). 11/2011; 108(45):18260-5. DOI:10.1073/pnas.1108228108
Source: PubMed

ABSTRACT Modified tetrapyrroles such as chlorophyll, heme, siroheme, vitamin B(12), coenzyme F(430), and heme d(1) underpin a wide range of essential biological functions in all domains of life, and it is therefore surprising that the syntheses of many of these life pigments remain poorly understood. It is known that the construction of the central molecular framework of modified tetrapyrroles is mediated via a common, core pathway. Herein a further branch of the modified tetrapyrrole biosynthesis pathway is described in denitrifying and sulfate-reducing bacteria as well as the Archaea. This process entails the hijacking of siroheme, the prosthetic group of sulfite and nitrite reductase, and its processing into heme and d(1) heme. The initial step in these transformations involves the decarboxylation of siroheme to give didecarboxysiroheme. For d(1) heme synthesis this intermediate has to undergo the replacement of two propionate side chains with oxygen functionalities and the introduction of a double bond into a further peripheral side chain. For heme synthesis didecarboxysiroheme is converted into Fe-coproporphyrin by oxidative loss of two acetic acid side chains. Fe-coproporphyrin is then transformed into heme by the oxidative decarboxylation of two propionate side chains. The mechanisms of these reactions are discussed and the evolutionary significance of another role for siroheme is examined.

0 0
1 Bookmark
  • [show abstract] [hide abstract]
    ABSTRACT: The alphaproteobacterium Magnetospirillum gryphiswaldense synthesizes magnetosomes, which are membrane-enveloped crystals of magnetite. Here we show that nitrite reduction is involved in redox control during anaerobic biomineralization of the mixed-valence iron oxide magnetite. The cytochrome cd1-type nitrite reductase NirS shares conspicuous sequence similarity with NirN that is also encoded within a larger nir cluster. Deletion of any one of these two nir genes resulted in impaired growth and smaller, fewer and aberrantly shaped magnetite crystals during nitrate reduction. However, whereas nitrite reduction was completely abolished in ΔnirS, attenuated but significant nitrite reduction occurred in ΔnirN, indicating that only NirS is a nitrite reductase in M. gryphiswaldense. However, ΔnirN produced a different form of periplasmic d1 heme which was not noncovalently bound to NirS, indicating that NirN is required for full reductase activity by maintaining a proper form of d1 heme for holo-cytochrome cd1 assembly. In conclusion, we for the first time assign a physiological function to NirN, and demonstrate that effective nitrite reduction is required for biomineralization of WT crystals, probably by contributing to oxidation of ferrous iron under oxygen-limited conditions.
    Journal of bacteriology 07/2013; · 3.94 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: The periplasmic cytochrome cd1 nitrite reductase NirS occurring in denitrifying bacteria such as the human pathogen Pseudomonas aeruginosa contains the essential tetrapyrrole cofactors heme c and heme d1. Whereas the heme c is incorporated into NirS by the cytochrome c maturation system I, nothing is known about the insertion of the heme d1 into NirS. Here, we show by co-immunoprecipitation that NirS interacts with the potential heme d1 insertion protein NirN in vivo. This NirS-NirN interaction is dependent on the presence of the putative heme d1 biosynthesis enzyme NirF. Further, we show by affinity co-purification that NirS also directly interacts with NirF. Additionally, NirF is shown to be a membrane anchored lipo-protein in P. aeruginosa. Finally, the analysis by UV-visible absorption spectroscopy of the periplasmic protein fractions prepared from the P. aeruginosa wild type and a P. aeruginosa ΔnirN mutant shows that the cofactor content of NirS is altered in the absence of NirN. Based on our results, we propose a potential model for the maturation of NirS in which the three proteins NirS, NirN and NirF form a transient, membrane-associated complex in order to achieve the last step of heme d1 biosynthesis and insertion of the cofactor into NirS.
    Bioscience Reports 05/2013; · 1.88 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Living entities are unimaginable without means to harvest free energy from the environment, that is, without bioenergetics. The quest to understand the bioenergetic ways of early life therefore is one of the crucial elements to understand the emergence of life on our planet. Over the last few years, several mutually exclusive scenarios for primordial bioenergetics have been put forward, all of which are based on some sort of empirical observation, a remarkable step forward from the previous, essentially untestable, ab initio models. We here try to present and compare these scenarios while at the same time discussing their respective empirical weaknesses. The goal of this article is to harness crucial new expertise from the entire field by stimulating a larger part of the bioenergetics community to become involved in "origin-of-energy-metabolism" research. This article is part of a Special Issue entitled: 18th European Bioenergetic Conference.
    Biochimica et Biophysica Acta 12/2013; · 4.66 Impact Factor

Full-text (2 Sources)

Available from
Sep 19, 2013