Haem biosynthesis in anaerobic organisms
A haem group
Oeiras, 23.04.09
Haem cofactors are essential for the function of key proteins involved in a large array of metabolic processes. However, the enzymes involved in their biosynthesis remain uncharacterized in anaerobic organisms. To fill this gap the Molecular Genetics of Microbial Resistance Laboratory (and co-workers) recently characterized several of these proteins and the data provided insights for an alternative haem biosynthetic pathway present in some anaerobic bacteria and archaea. The results are published in the March issue of the Biochemical Journal.
The authors suggest that the production of the haem group in primitive anaerobic enviroments probably required a different set of enzymes and that only later, as molecular oxygen became more abundant, the pathway involving several oxidative steps in the synthesis of haems became the more common route.
Biochem. J. (2009) Immediate Publication, doi:10.1042/BJ20090151
Functional characterization of the early steps of tetrapyrrole biosynthesis and modification in Desulfovibrio vulgaris Hildenborough
Susana A. L. Lobo, Amanda Brindley, Martin J. Warren and Lígia M. Saraiva
The article reports the comprehensive analysis of the haem biosynthetic pathway in the environmentally important anaerobic organism D. vulgaris Hildenborough.
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Several recombinant enzymes required for the transformation of 5-aminolevulinic acid into sirohydrochlorin and vitamin B12, were studied using molecular genetics and biochemistry methodologies. We show that porphobilinogen synthase (HemB) is a homohexamer zinc-dependent enzyme, and that porphobilinogen deaminase (HemC) contains a dipyrromethane cofactor. Interestingly, uroporphyrinogen III synthase is found fused with an uroporphyrinogen III methyltransferase (HemD-CobA) and its function was addressed by analysing not only the whole protein but also by dissecting the gene and studying the role of the individual protein domains. This study allowed to correct the genome annotation of a putative bifunctional precorrin-2 dehydrogenase/sirohydrochlorin ferrochelatase which was in fact shown to act only as a dehydrogenase and is simply capable of synthesizing sirohydrochlorin rather than sirohaem. |
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In summary, the research described in this paper outlines how the basic tetrapyrrole framework is synthesized up to the first branch point, which is proposed to be sirohydrochlorin. The identification of bifunctional CobA/HemD is consistent with uroporphyrinogen III not being a branch point in the bifurcated pathway and represents a useful marker for an alternative haem biosynthetic route, which has been previously hypothesized to occur in some Desulfovibrio species and archaea.
