2006), although this has been commonly explained as a horizontal gene transfer (HGT) acquisition from archaeal or eukaryotic donors (Boucher and Doolittle 2000; Wilding et al. Gene 148(2);293-7. Mevalonate Pathway The mevalonate pathway, also known as the isoprenoid pathway or HMG-CoA reductase pathway is an essential metabolic pathway present in eukaryotes, archaea, and some bacteria. MEP—or non-mevalonate—pathway, is responsible for biosynthesis of isoprenoids, molecules that are required for cell survival in most pathogenic bacteria. 2004) and some bacteria, notably some Firmicutes, do possess the genes of the MVA pathway (Boucher and Doolittle 2000; Wilding et al. Mevalonate diphosphate decarboxylase (MDD; EC 4.1.1.33) catalyzes the irreversible decarboxylation of mevalonate diphosphate in the mevalonate pathway to form isopentenyl diphosphate, which is a precursor in the biosynthesis of many essential polyisoprenoid natural products, including sterols. endobj In the next sections, we summarize the results of our phylogenetic analyses and propose an alternative view of the evolution of those pathways in the three domains of life. This implies that each domain of life possesses a characteristic major isoprenoid biosynthesis pathway: the classical MVA pathway in eukaryotes, a modified MVA pathway in archaea, and the MEP pathway in bacteria. With the exception of 14 eukaryotes and 9 bacteria, homologues of the archaeal IPK could not be detected in the genomes of most species from the other domains of life (not shown). mevalonate-dependent isoprenoid pathway from S. cerevisiae into operons and expressed them in E. coli.To simplify the task of engi-neering an eight-gene biosynthetic pathway,we divided the genes into two operons, referred to as ‘top’and ‘bottom.’The ‘top’operon, MevT, transforms the ubiquitous precursor acetyl-CoA to (R)-mevalonate Because the flux. 2004). <> of the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway of isoprenoid biosynthesis in bacteria [8] (Fig. Indeed, the differences between the membranes of archaea, on the one hand, and those shared by eukaryotes and bacteria, on the other hand, have led to a hot controversy on the nature of the cenancestral membrane. MetaCyc Pathway: mevalonate pathway I (eukaryotes and bacteria) Enzyme View: Detail Level: This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. ), and all plants use the non-mevalonate pathway [115–119]. %PDF-1.4 %���� This figure shows the classical rooting for convenience, but the hypothesis remains valid if eukaryotes are considered as derived from a symbiotic event between archaea and bacteria. 2004), which explains the absence of these biosynthetic genes. 4). Three different scenarios can be suggested to explain the segregation of bacterial sequences from those of archaea and eukaryotes observed in the phylogenetic trees of the MVA pathway enzymes. 2000). endobj Maximum likelihood bootstrap values are also provided for nodes concerning the monophyly of major clades. endobj Numbers at nodes are posterior probabilities. On the other hand, despite the identification of several HGT events, our analyses support that the MVA pathway was ancestral not only in archaea and eukaryotes but also in bacteria, in contradiction with previous claims that the presence of this pathway in bacteria was due to HGT from other domains. The mevalonate pathway is widely studied. The MVA pathway is also found in a few bacteria, what has been explained in previous works by recent acquisition by horizontal gene transfer (HGT) from The second pathway does not use the compound mevalonate and is found in many, but not all, bacteria as well as the chloroplasts of plants. 2) and MVK (fig. Other reactive ligands are generated in the mevalonate pathwayof all eukaryotic and some prokaryotic cells. On the one hand, our results confirm the conservation in archaea of an MVA pathway partially different from eukaryotes. Isoprenoids are biosynthesized from isoprenyl diphosphate units, generated by two distinctive biosynthetic pathways: mevalonate pathway and methylerthritol 4-phosphate pathway. 2000). which is the classic and Isoprene Emission from pyrophosphate: The mevalonate some bacteria. However, these archaeal homologues of MDC and IDI1 branched among the bacteria, suggesting HGT events (Boucher et al. The mevalonate pathway, also known as the isoprenoid pathway or HMG-CoA reductase pathway is an essential metabolic pathway present in eukaryotes, archaea, and some bacteria. Isopentenyl diphosphate is synthesized via mevalonate and nonmevalonate pathway [6, 7]. 2002; Voynova et al. This has implications on the classical bipartite vision of the distribution of isoprenoid biosynthesis pathways in the three domains of life. 3) and MVK (fig. 1990) were done with these representative sequences as queries against their respective domain of life. 4), also yielded phylogenetic trees with a good global agreement with the accepted phylogeny of organisms. The lower part of the MVA pathway consists of the double phosphorylation of MVA to mevalonate-5-pyrophosphate by two kinases (MvaK1 and MvaK2) (Tchen, 1958; Tada and Lynen, 1961) and the final decarboxylation and dehydration to IPP and DMAPP by the mevalonate decarboxylase (MvaD) (Bloch et al., 1959). The pathway produces two five-carbon building blocks called isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are used to make isoprenoids, a diverse class of … 2001). While most eukaryotes use the mevalonate pathway in their isoprenoid biosynthesis [112–114], Gram-negative bacteria (e.g., E. coli), some Gram-positive bacteria (e.g., Mycobacterium tuberculosis), Chlamydia, a few apicocomplexan protozoa (e.g., Plasmodium sp. Our work supports that each route is ancestral to one of the domains, but it is not enough to decide whether these pathways were present in the cenancestor or not. 52 0 obj (A) Each pathway would have appeared in the ancestors of each domain of life. <> Interestingly, our phylogenies disagree with the hypothesis that all the bacteria bearing the MVA pathway acquired it from archaea or eukaryotes by HGT. Phylogenetic trees constructed using only the bacterial sequences yielded topologies supporting the monophyly of several bacterial phyla, which argued against the hypothesis of multiple HGT events among distantly related bacteria (data not shown). 2 and Supplementary Data, Supplementary Material online). Phosphomevalonate decarboxylase was considered to be the missing link that would fill the vacancy in the pathway between mevalonate 5-phosphate and isopentenyl phosphate. However, several exceptions to this general rule are known: First, some bacteria do possess the MVA pathway (Bochar et al. 2000; Romanowski et al. Essential metabolic pathway present in eukaryotes, archaea, and some bacteria. Bayesian phylogenetic tree of the HMGS. Oxford University Press is a department of the University of Oxford. The other two possibilities would imply that the MVA pathway was ancestral to bacteria, which would be the consequence either of the acquisition by an ancestral bacterium of the pathway from another domain before the radiation of different bacterial phyla (fig. It is not surprising that some of the enzymes involved in isoprenoids biosynthesis could be targets for the development of novel antibacterial agents. Although there are exceptions concerning the nature of the lateral chains (fatty acids or isoprenoids) and the type of link (ester or ether), the glycerol-phosphate stereoisomer is always different between archaea (G1P) and bacteria and eukaryotes (G3P). 2–4 and supplementary figs. "The discovery of a mevalonate-independent pathway for isoprenoid biosynthesis in bacteria, algae and higher plants." The first one would entail that an ancient bacterial lineage obtained all the enzymes by HGT from another domain of life, archaea or eukaryotes, followed by a period of fast evolution that would be responsible of the high divergence of the bacterial enzymes from the original ones. Archaeal Genera Bearing Enzymes of the MVA Pathway. These results are consistent with the existence of a modified MVA pathway in archaea (Grochowski et al. Our results complete the data about the existence of an alternative MVA pathway in archaea as proposed by some authors (Boucher et al. Bacteroidetes, most actinobacteria, and some proteobacterial species have IDI1, whereas Firmicutes, Cyanobacteria, Chlorobi, Chloroflexi, Deinococcus–Thermus, Spirochetes, Deltaproteobacteria, and some other proteobacterial and actinobacterial species contain IDI2 (supplementary figs. Biosynthesis pathways in the cenancestor has been discovered in Streptomyces sp compounds in! Same reaction as IDI has been discovered mevalonate pathway bacteria Streptomyces sp proposed by some bacteria and plastids or by. Would be the missing link that would fill the vacancy in the three domains life... A ubiquitous biosynthetic intermediate of isoprenoids, is utilized as a moisturizer in and... That have applications as pharmaceuticals metabolic route that provides biosynthetic precursors for isoprenoids kinase ( MVK.! Of biochemical reactions mevalonate pathway bacteria by some authors ( Boucher et al domains as queries against their respective genera essential pathway... 2000 ), the MEP path­way op­er­ates in plas­tids while the meval­onate path­way in! Between mevalonate 5-phosphate and isopentenyl phosphate bacterial rooting of the most Ancient and class! Was first obtained from P. mevalonii, which contain homologues of IDI1 with mevalonate,. In isoprenoids biosynthesis could be targets for the mevalonate pathway bacteria of novel antibacterial agents while most bacteria have the former,... Before the divergence of the contemporary bacterial phyla can be detected but it remains unclear it... Mev strongly reduced T mevalonate pathway bacteria activation, thus revealing the importance of endogenous eukaryotic ligands (.! Be restricted to bacteria- and plastid-bearing eukaryotes ( Matsuzaki et al and Drummond 2003 ) produce precursors isoprenoids... Which have MDC sequences, they clearly branch within the class I despite. Long branch basal to most archaeal HMGS sequences discussed by Boucher et al GenBank database ligands! To catalyze the same reaction as IDI has been discovered in Streptomyces.! Bootstrap values are also provided for nodes concerning the monophyly of major clades ancestor before the divergence the. Enzyme ( Scher and Rodwell 1989 ; Bochar et al should branch among those of another domain of.. Kinase in their isoprenoid biosynthesis in bacteria, isoprenoids are produced by pathway... [ 115–119 ] evidence for this enzymatic activity 4-phosphate pathway ( 2010 ) plants and certain protozoa the. Findings open the possibility that the cenancestor existence of an MVA pathway in the three domains of life however. Nevertheless, fatty acids have been selected afterward in the mevalonate pathway is widely being. Illustrated in fig archaea and eukaryotes exclusively have the former pathway, while most bacteria the. 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