Table 1.
Orthologous and Nonorthologous Metabolic Pathways and Enzymes in Archaea
| Pathway | Enzymes (genes) in the pathway | Orthologs of bacterial genes found in all four archaeal genomes | Genes missing in all four archaeal genomes | Nonorthologous gene displacement: orthologs of bacterial genes found only in some of the archaeal genomes | Consequences for archaeal metabolism |
| Glycolysis | hexokinase (glk), phosphoglucoisomerase (pgi), phosphofructokinase (pfkA), aldolase (fba/dhnA), triosephosphate isomerase (tpi), glyceraldehyde 3-phosphate dehydrogenase (gapA), 3-phosphoglycerate kinase (pgk), phosphoglyceromutase (pgm/yibO), enolase (eno), pyruvate kinase (pykA) | dhnA, tpi, gapA,pgk, pgm , eno | glk pfkA | pgi is present only in Mj; pykA is present in Mj and Ph, not found in Mt and Af | bacterial-type hexokinase and phosphofructokinase are apparently displaced by nonorthologous ADP-dependent enzymes; the lack of pyruvate kinase in Mt and Af is probably compensated by phosphoenolpyruvate synthase working in the reverse direction. |
| Gluconeogenesis | phosphoenolpyruvate synthase (ppsA), enolase (eno), phosphoglyceromutase (pgm), 3-phosphoglycerate kinase (pgk), glyceraldehyde 3-phosphate dehydrogenase (gapA), triosephosphate isomerase (tpi), aldolase (fba/dhnA), fructose bisphosphatase (fbp), phosphoglucoisomerase (pgi) | ppsA, eno, pgm, pgk, gapA, tpi, dhnA | fbp | pgi is present only in Mj, not found in Mt, Af, and Ph | other phosphohexomutases (e.g., phosphomannomutase) are probably used for polysaccharide biosynthesis in Mt, Af, and Ph. |
| Pentose phosphate shunt and pentose biosynthesis | glucose-6-phosphate dehydrogenase (zwf), 6-phosphogluconate dehydrogenase (gnd), transketolase (tktA); transaldolase (talA), pentose-5phosphate-3-epimerase (yhfD), ribose 5-phosphate isomerase (rpiA), deoxyribose-phosphate aldolase (deoC) | rpiA | zwf, gnd | tktAgene is split in Mj, absent in Mt, Af, and Ph; talA andyhfD are present in Mj, not in Mt, Af, or Ph;deoC is present only in Mt | this pathway is not functional in any of these archaea. The mechanism of pentose phosphate biosynthesis is not clear. A predicted DhnA-type aldolase that is highly conserved in all four archaea (MJ0400, MJ1585; MTH579; AF0108, AF0230; PH0082) may catalyze the formation of ribose from glyceraldehyde3-phosphate and acetaldehyde. Alternatively, in Mt, this reaction might be catalyzed by the DeoC ortholog (MTH818). |
| Entner– Doudoroff pathway | glucose-6-phosphate dehydrogenase (zwf), 6-phosphogluconate dehydratase (edd), 2-keto-3-deoxy-6-phosphogluconate aldolase (eda) | edd | zwf, eda | archaea lack the classical Entner–Doudoroff path-way and instead appear to possess a modified, nonphosphorylated ver-sion. In Mj, Af, and Mt, members of the above new family of aldolases may function in this pathway as 2-keto3-de-oxygluconate aldolase (a nonorthologous displace-ment of Eda). The archaeal gluconate dehydratase remains unknown, which precludes a complete reconstruction of this pathway. | |
| TCA cycle | citrate synthase (gltA), aconitase (acnA), isocitrate dehydrogenase (icd), | acnA, icd, sucC, sucD, frdA, frdB, | sucA, sucB | gltA is present in Mt and Af, but not in Mj or Ph; Ph has | Mt and Af can reduce α-ketoglutarate to citrate and further to succinate |
| α-ketoglutarate dehydrogenase (sucA, sucB), succinylCoA synthase (sucC, sucD), fumarate reductase (frdA, frdB), fumarase (fumA), malate dehydrogenase (mdh) | fumA, mdh | fumA and, possibly, acnA genes | or succinyl-CoA; in Mj only the part from oxaloacetate to succinyl-CoA is operative. | ||
| Purine biosynthesis | phosphosphoribosylpyrophosphate synthase (prsA), amidophosphoribosyltransferase (purF), GAR synthase (purD), GAR transformylase (purN/purT), FGAM synthase (purL), AIR synthase (purM), NCAIR synthase (purK), NCAIR mutase (purE), SAICAR synthase (purC), adenylosuccinate lyase (purB), AICAR transformylase (purH2), IMP cyclohydrolase (purH1), adenylosuccinate synthase (purA), IMP dehydrogenase (guaB), GMP synthase (guaA), | prsA, purF, purD, purL, purM, purE, purC,purB, purA, guaA | purK,purH2 | purT is present in Mj and Ph but not in Mt and Af; purH1 is present only in Af; guaB is present in Mj, Mt, and Ph, but not in AF | all four archaea are probably capable of purine synthesis de novo; carboxylation of AIR probably occurs spontaneously. The still unidentified enzymes that catalyze formylation of SAICAR and AICAR in all four archeaea and formylation of GAR in Mt and Af apparently use formate and ATP as substrates. IMP dehydrogenase is missing AF and is probably displaced by a nonorthologous dehydrogenase. |
| Pyrimidine biosynthesis | carbamoylphosphate synthase (carA,carB), aspartate carbamoyltransferase (pyrB), dihydroorotase (pyrC/ygeZ), dihydroorotate dehydrogenase (pyrD), orotate phosphoribosyl-transferase (pyrE), orotidine-5’-phosphate decarboxylase (pyrF), UMP kinase (pyrH), NDP kinase (ndk), CTP synthase (pyrG) | pyrB, ygeZ, pyrD, pyrE, pyrF, pyrH, ndk, pyrG | none | carA and carB are missing in Ph | Mj, Mt, Af and probably Ph are capable of pyrimidine synthesis de novo. The identity of carbamoylphosphate synthase in Ph remains unclear. |
| Histidine biosynthesis | phosphosphoribosylpyrophosphate synthase (prsA), ATP-phosphoribosyltransferase (hisG), phosphoribosyl-ATP pyrophosphatase (hisI2), phosphoribosyl-AMP cyclohydrolase (hisI1), 5′-ProFAR isomerase (hisA), imidazoleglycerol phosphate synthase (hisH,hisF), imidazoleglycerol phosphate dehydratase (hisB2), histidinol phosphate aminotransferase (hisC), histidinol phosphatase (hisB1), histidinol dehydrogenase (hisD) | prsA, hisG, hisI1, hisA, hisH, hisF, hisB2, hisC, hisD | none | hisI2 is present in Mj and Mt, but not in Af; hisB1 is found only in Mj;prsA and hisC genes are present in Ph | Mj, Mt, and Af are all capable of histidine biosynthesis; phosphoribosyl-ATP pyrophosphatase in Af is probably displaced by some other ATP/ADPase; all archaea encode distant homologs of yeast histidinol phosphatase (HD superfamily hydrolases; Aravind and Koonin 1998b), one of which might displace HisB1 in Af and Mt. |
| Branched chain amino acids biosynthesis | threonine deaminase (ilvA), acetohydroxyacid synthase (ilvB, ilvN), acetohydroxyacid isomeroreductase (ilvC), dihydroxyacid dehydratase (ilvD), 2-isopropylmalate synthase (leuA), isopropylmalate isomerase (leuC,leuD), 3-isopropyl-malate | ilvA, ilvB, ilvN, ilvC, ilvD, leuA, leuC, leuD, leuB, ilvE | none | none | all enzymes of leucine, isoleucine, and valine biosynthesis in bacteria, archaea, and yeast are orthologous. |
| dehydrogenase (leuB), glutamate transaminase (ilvE) | |||||
| Aromatic | 3-deoxyheptulosonate | aroD, aroE, | aroG, | none | the mechanism of |
| amino acids biosynthesis | 7-phosphate synthase (aroG/kdsA), 3-dehydroquinate synthase (aroB), 3-dehydroquinate dehydratase (aroD), shikimate dehydrogenase (aroE), shikimate kinase (aroK), 5-enolpyruvoylshikimate 3-phosphate synthase (aroA), chorismate synthase (aroC), chorismate mutase (pheA1), prephenate dehydratase (pheA2), prephenate dehydrogenase (tyrA2), tyrosine aminotransferase (tyrB), antranilate synthase (trpD1, trpE), antranilate phosphoribosyl-transferase (trpD2), phosphoribosylantranilate isomerase (trpC2), indole-glycerol phosphate synthase (trpC1), tryptophan synthase (trpA, trpB) | aroA, aroC, pheA1, pheA2, tyrA2, tyrB, trpD1, trpE, trpD2, trpC2, trpC1, trpA, trpB | aroB, aroK | 3-dehydroquinate synthesis remains unclear; shikimate phosphorylation in all autotrophic archaea is probably performed by an archaea-specific kinase. | |
| Threonine biosynthesis | aspartokinase (thrA1), aspartate semialdehyde dehydrogenase (asd), homoserine dehydrogenase (thrA2), homoserine kinase (thrB), threonine synthase (thrC) | thrA1, asd, thrA2, thrC | none | thrB is present in Mj and Ph, but not in Mt and Af | in Mt and Af, homoserine kinase is probably displaced by a different kinase. |
| Methionine biosynthesis | aspartokinase (metL1), aspartate semialdehyde dehydrogenase (asd), homoserine dehydrogenase (metL2), homoserine transsuccinylase (metA), cystathionine γ-synthase (metB), β-cystathionase (metC), methionine synthase (metE/metH) | metL1, asd, metL2, metE | metA, | metB/metC is found only in Ph, not in Mj, Mt, or Af | in all four archaea, the three steps leading from homoserine to homocysteine are probably displaced by a single reaction catalyzed by a sulfur transferase. |
| Arginine biosynthesis | acetylglutamate synthase (argA2), acetylglutamate kinase (argB), acetylglutamate phosphate reductase (argC), acetylornithine aminotransferase (argD), acetylornithinase (argE), ornithine carbamoyltransferase (argF), argininosuccinate synthase (argG), argininosuccinate lyase (argH) | argA2, argB, argC, argD, argF, argH | none | argE is present in Mj, Af; and Ph, but not in Mt; argG is present in Mj, Mt and Af but not in Ph | in Mt, acetylornithinase is probably displaced by a different acetyltransferase. |
| NAD biosynthesis | aspartate oxidase (nadB), quinolinate synthase (nadA), quinolinate phosphoribosyltransferase (nadC), nicotinic acid mononucleotide adenylyltransferase (nadD), deamidoNAD ammonia ligase (nadE) | nadB, nadC, nadE | none | nadA is present in Mj, Mt, and Ph, but not in AF | nadA is probably displaced in AF by a different enzyme; nadD gene (predicted E. coli yneB) remains unidentified in bacteria and archaea. |
| Riboflavin biosynthesis | GTP cyclohydrolase II (ribA), pyrimidine deaminase (ribD1), pyrimidine reductase (ribD2), | ribD2, ribB, ribE | ribC | ribA and ribD1 are present in Af but not in Mj or Mt | ribC is displaced by an archaea-specific riboflavin synthase (Eberhardt et al., |
| 3,4-dihydroxybutanone-4phosphate synthase (ribB), 6,7-dimethyl-8-ribityllumazine synthase (ribE), riboflavin synthase (ribC) | 1997); the mechanism of 2,5-diamino-6-ribosylamino-4-pyrimidone 5′-phosphate formation Mj and Mt remains unclear. | ||||
| Siroheme biosynthesis | Glutamyl-tRNA reductase (hemA), glutamate 1-semialdehyde aminotransferase (hemL), probilinogen III synthase (hemB), hydroxymethylbilane synthase (hemC), uroporphyrinogen III synthase (hemD), uroporphirinogen methyltransferase (cysG2), dimethyluroporphirinogen III dehydrogenase (cysG1) | hemA, hemL, hemB, hemC, hemD, cysG2, cysG1 | none | none | all enzymes of siroheme biosynthesis in archaea are orthologous to bacterial ones. |
| Cobalamin biosynthesis | uroporphyrinogen III methylase (cysG2), precorrin-2 methylase (cbiL), precorrin-3B methylase (cbiH), precorrin-4 methylase (cbiF), precorrin-6A reductase (cbiJ), precorrin 6B methylase (cbiE), precorrin 6B decarboxylase (cbiT), precorrin-8x isomerase (cbiC), cobyrinic acid a,c-diamide synthase (cbiA), cobalt insertion protein (cobN), cob(I)alamin adenosyltransferase (cobA), cobyric acid synthase (cbiP), cobyric acid aminotransferase (cobD), cobinamide synthase (cbiB), nicotinate-nucleotide:dimethylbenzimidazole phosphoribosyltransferase (cobT), cobalamin synthase (cobS) | cysG2, cbiH, cbiF, cbiE, cbiC, cbiA, cbiP, cbiB, cobS | cobA, cobD | cbiL, cbiJ, cbiT, and cobN are present in Mj and Mt but not in Af;cobT is found only in Af | in Mj, Mt, and Af, cobAand cobD gene products are probably displaced by archaea-specific adenosyl- and aminotransferases, respectively; it is not clear whether this pathway is functional in Af. |
| Biotin biosynthesis | pimeloyl-CoA synthetase (bioW), 7-keto-8-aminopelargonate synthetase (bioF), 7,8-diaminopelargonate aminotransferase (bioA), dethiobiotin synthetase (bioD), biotin synthetase (bioB), biotin-[acetyl-CoA carboxylase] holoenzyme synthetase (birA) | none | none | all the enzymes of the pathway are present in Mj but only one or two enzymes can be found in Mt, Af, and Ph | probably only Mj is capable of biotin biosynthesis. |
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↵The genes and pathways follow the biochemical data and nomenclature described for E. coli and S. typhimurium (Neidhardt et al. 1996). Genes coding for multidomain proteins with more than one enzymatic activity are divided into separate domains, starting from the amino-terminal domain. Known cases of nonorthologous gene displacements are indicated with a slash; genes encoding different subunits of the same enzyme are separated by commas.
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↵6-Phosphogluconate dehydratase gene (edd) is apparently present in Mj, Mt, and Af, but these ORFs probably function as dihydroxyacid dehydratases (ilvD), which is a paralog ofedd.
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↵Most enzymes of these pathways are not encoded in thePyrococcus horikoshii genome; exceptions are indicated.
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↵Orthologs of B. subtilis pgm gene, corresponding to the E. coli yibO.
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↵Orthologs of B. subtilis gene bioW,not found in E. coli.
