Methanocaldococcus jannaschii Uses a Modified Mevalonate Pathway for Biosynthesis of Isopentenyl Diphosphate

  title={Methanocaldococcus jannaschii Uses a Modified Mevalonate Pathway for Biosynthesis of Isopentenyl Diphosphate},
  author={Laura L. Grochowski and Huimin Xu and Robert H. White},
  journal={Journal of Bacteriology},
  pages={3192 - 3198}
ABSTRACT Archaea have been shown to produce isoprenoids from mevalonate; however, genome analysis has failed to identify several genes in the mevalonate pathway on the basis of sequence similarity. A predicted archaeal kinase, coded for by the MJ0044 gene, was associated with other mevalonate pathway genes in the archaea and was predicted to be the “missing” phosphomevalonate kinase. The MJ0044-derived protein was tested for phosphomevalonate kinase activity and was found not to catalyze this… 
Evidence of a Novel Mevalonate Pathway in Archaea
It is proposed that a yet unidentified ATP-independent decarboxylase acts upon mevalonate 3,5-bisphosphate, yielding isopentenyl phosphate, which is subsequently phosphorylated by the known isopel phosphate kinase from T. acidophilum to generate the universal isoprenoid precursor, IPP.
Characterization of thermophilic archaeal isopentenyl phosphate kinases.
An analysis of the genomes of several members of the Archaea failed to identify genes for the enzymes required to convert phosphomevalonate to IPP in eukaryotes, but a blast search using the MJ protein as a probe revealed a subfamily of amino acid kinases that include the fosfomycin resistance protein fomA, which deactivates the antibiotic by phosphorylation of its phosphonate residue in a reaction similar to the conversion of IP toIPP.
A new class of adenylate kinase in methanogens is related to uridylate kinase
It is reported that the MJ0458 gene product is a second type of archaeal adenylate kinase, AdkB, which is different from the established Archaeal-specific adenYLate Kinase in both sequence and predicted tertiary structure.
Modified mevalonate pathway of the archaeon Aeropyrum pernix proceeds via trans-anhydromevalonate 5-phosphate
The partially identified “modified” mevalonate pathway of the majority of archaea is elucidated using information from comparative genomic analysis, which shows that the pathway passes through a previously unrecognized metabolite, trans-anhydromevalonate 5-phosphate.
Identification in Haloferax volcanii of Phosphomevalonate Decarboxylase and Isopentenyl Phosphate Kinase as Catalysts of the Terminal Enzyme Reactions in an Archaeal Alternate Mevalonate Pathway
This results represent the first experimental demonstration in H. volcanii of both the phosphomevalonate decarboxylase and isopentenyl phosphate kinase reactions that are required for an alternate mevalonates pathway in an archaeon.
Discovery of a metabolic alternative to the classical mevalonate pathway
Key to this pathway is the catalytic actions of a newly uncovered enzyme, mevalonate phosphate decarboxylase (MPD) and IPK and these two discoveries suggest that unforeseen variation in isoprenoid metabolism may be widespread in nature.
Identification and Characterization of an Archaeon-Specific Riboflavin Kinase
The riboflavin kinase in Methanocaldococcus jannaschii has been identified as the product of the MJ0056 gene, which represents a unique CTP-dependent family of kinases and fills another gap in the archaeal flavin biosynthetic pathway.
Promiscuity of methionine salvage pathway enzymes in Methanocaldococcus jannaschii.
Data suggest that MTIP and MTRI may function in a novel pathway for recycling the 5'-deoxyadenosine moiety of SAM in M. jannaschii, and may enable biosynthesis of 6-deoxy-5-ketofructose 1-phosphate (DKFP), an essential intermediate in aromatic amino acid biosynthesis.


Biosynthesis of isoprenoids via mevalonate in Archaea: the lost pathway.
Orphan members of the galactokinase, nucleoside monophosphate kinase, and pyrophosphohydrolase families in archaeal genomes were evaluated as candidate enzymes for the three missing functions in archaea, whose participation in isoprenoid biosynthesis is amenable to biochemical and genetic investigation.
Identification of Coenzyme M Biosynthetic Phosphosulfolactate Synthase
An enzyme from that organism, (2R)-phospho-3-sulfolactate synthase (ComA), that catalyzes the first step in coenzyme M biosynthesis, and its Mg2+-dependent enzyme reaction mechanism may be analogous to one proposed for enolase.
Archaeal Shikimate Kinase, a New Member of the GHMP-Kinase Family
The case of archaeal shikimate kinase illustrates the efficacy of techniques based on reconstruction of metabolism from genomic data and analysis of gene clustering on chromosomes in finding missing genes.
Mevalonic acid is partially synthesized from amino acids in Halobacterium cutirubrum: a 13C nuclear magnetic resonance study
C nuclear magnetic resonance revealed an unusual pathway for the biosynthesis of lipids in Halobacterium cutirubrum and H. halobium, and a general scheme is proposed to account for the contribution of lysine-to-lipid biosynthesis.
Identification of an Archaeal Type II Isopentenyl Diphosphate Isomerase in Methanothermobacter thermautotrophicus
A plasmid-encoded copy of the ORF complemented IPP isomerase activity in vivo in Salmonella enterica serovar Typhimurium strain RMC29, which contains chromosomal knockouts in the genes for type I IPP wasomerase (idi) and 1-deoxy-D-xylulose 5-phosphate (dxs).
Isopentenyl diphosphate biosynthesis via a mevalonate-independent pathway: isopentenyl monophosphate kinase catalyzes the terminal enzymatic step.
  • B. M. Lange, R. Croteau
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1999
Cl cloning from peppermint and E. coli resulted in the rapid production of monoterpenes and sesquiterpenes, confirming that isopentenyl monophosphate is the physiologically relevant, terminal intermediate of the deoxyxylulose 5-phosphate pathway.
Biosynthetic pathways in Methanospirillum hungatei as determined by 13C nuclear magnetic resonance
The main metabolic pathways in Methanospirillum hungatei GP1 were followed by using 13C nuclear magnetic resonance, with 13C-labeled acetate and CO2 as carbon sources, indicating that the oxidative or reductive pentose phosphate pathways are not functioning at significant rates.
Origins and evolution of isoprenoid lipid biosynthesis in archaea
This investigation of the isoprenoid biosynthesis apparatus of archaea on small and large phylogenetic scales reveals that it evolved through a combination of evolutionary processes, including the co‐option of ancestral enzymes, modification of enzymatic specificity, orthologous and non‐orthologous gene displacement, integration of components from eukaryotes and bacteria and lateral gene transfer within and between archaeal orders.
Bacterial origin for the isoprenoid biosynthesis enzyme HMG-CoA reductase of the archaeal orders Thermoplasmatales and Archaeoglobales.
The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase or HMGR) fulfills an essential role in archaea, as it is required for the synthesis of isoprenoid ethers, the main