ArticleACS chemical biology2012
Comparative genomics guided discovery of two missing archaeal enzyme families involved in the biosynthesis of the pterin moiety of tetrahydromethanopterin and tetrahydrofolate.
Article in ACS chemical biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 30 citations in OpenAlex.
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- Metabolic traits of an uncultured archaeal lineage--MSBL1--from brine pools of the Red Sea.Scientific reports · 2016Article
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- Structure of the methanofuran/methanopterin-biosynthetic enzyme MJ1099 from Methanocaldococcus jannaschii.Acta crystallographica. Section F, Structural biology communications · 2014Article
- Biochemical characterization of a dihydroneopterin aldolase used for methanopterin biosynthesis in methanogens.Journal of bacteriology · 2014Article
- Variations in metabolic pathways create challenges for automated metabolic reconstructions: Examples from the tetrahydrofolate synthesis pathway.Computational and structural biotechnology journal · 2014Review
- Structure of dihydromethanopterin reductase, a cubic protein cage for redox transfer.The Journal of biological chemistry · 2014Article
- Discovery and characterization of the first archaeal dihydromethanopterin reductase, an iron-sulfur flavoprotein from Methanosarcina mazei.Journal of bacteriology · 2014Article
- Early bioenergetic evolution.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2013Review
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8 authors at 4 institutions in 1 country.
Funding
Abstract
C-1 carriers are essential cofactors in all domains of life, and in Archaea, these can be derivatives of tetrahydromethanopterin (H(4)-MPT) or tetrahydrofolate (H(4)-folate). Their synthesis requires 6-hydroxymethyl-7,8-dihydropterin diphosphate (6-HMDP) as the precursor, but the nature of pathways that lead to its formation were unknown until the recent discovery of the GTP cyclohydrolase IB/MptA family that catalyzes the first step, the conversion of GTP to dihydroneopterin 2',3'-cyclic phosphate or 7,8-dihydroneopterin triphosphate [El Yacoubi, B.; et al. (2006) J. Biol. Chem., 281, 37586-37593 and Grochowski, L. L.; et al. (2007) Biochemistry46, 6658-6667]. Using a combination of comparative genomics analyses, heterologous complementation tests, and in vitro assays, we show that the archaeal protein families COG2098 and COG1634 specify two of the missing 6-HMDP synthesis enzymes. Members of the COG2098 family catalyze the formation of 6-hydroxymethyl-7,8-dihydropterin from 7,8-dihydroneopterin, while members of the COG1634 family catalyze the formation of 6-HMDP from 6-hydroxymethyl-7,8-dihydropterin. The discovery of these missing genes solves a long-standing mystery and provides novel examples of convergent evolutions where proteins of dissimilar architectures perform the same biochemical function.
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