Mevalonic acid is partially synthesized from amino acids in Halobacterium cutirubrum: a 13C nuclear magnetic resonance study

Ekiel, Irena; Sprott, G. Dennis; Smith, Ian C. P.

doi:10.1128/jb.166.2.559-564.1986

Cited by 36 publications

(29 citation statements)

References 19 publications

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“…The discovery that the glutamic acid that was produced by the cells incorporates only one deuterium from [2,2,2-*H3]acetate is completely consistent with the proposed biosynthesis of a-ketoglutaric acid from acetate outlined in Figure 4. This pathway for the biosynthesis of a-ketoglutaric acid in methanogenic bacteria has been confirmed by carbon magnetic resonance spectroscopy (Ekiel et al, 1983(Ekiel et al, , 1984 and is consistent with the known metabolism of methanogenic bacteria (Fuchs & Stupperich, 1984;Whitman, 1985). Since the y protons of the glutamic acid exchange during acid hydrolysis (Cohen & Putter, 1970;White, 1980), the actual abundance of deuterium in the cellular glutamic acid should be slightly higher.…”

Section: Resultssupporting

confidence: 58%

Biosynthesis of the 1,3,4,6-hexanetetracarboxylic acid subunit of methanofuran

White¹

1987

Biochemistry

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2H-and 13C-labeled precursors were used to establish the pathway for the biosynthesis of the 1,3,4,6-hexanetetracarboxylic acid (TCA) component of methanofuran, which is found in some methanogenic bacteria. The extent and position of incorporation of label into TCA were measured from the mass spectrum of the tetramethyl ester of T C A that was prepared from methanofuran present in cells grown in the presence of labeled acetate. [2,2,2-2H3]Acetate was found to incorporate deuterium into two separate sites of the T C A molecule, with one on each side of the symmetrical molecule. One site was found to be labeled 37% with deuterium, the same as for the glutamic acid present in the cells; the other site was labeled 77% with deuterium, the same as for the malonate-derived compounds in the cells. An analogue of TCA, 1-hydroxy-1,3,4,6-hexanetetracarboxylic acid, found in methanofuran isolated from Methanobrevibacter smithii, was found to incorporate 13C2 units from [1,2-13C2]acetate into three positions of the molecule. One of the acetate 13C2 units was incorporated into the non-hydroxyl-containing side of the molecule (carbons 4, 5 , and 6 and the C-6 carboxylic acid group), and two acetate units were incorporated into the hydroxyl-containing side of the molecule (carbons 1, 2, and 3 and the C-1 carboxylic acid group). On the basis of this and additional information, it is concluded that T C A is biosynthesized by the condensation of a-ketoglutaric acid with malonic acid to form 1,1,2,4-butanetetracarboxylic acid, which is further condensed with a second molecule of malonate, in a series of reactions analogous to those observed during fatty acid biosynthesis, to form TCA.

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Section: Resultssupporting

confidence: 58%

Biosynthesis of the 1,3,4,6-hexanetetracarboxylic acid subunit of methanofuran

White¹

1987

Biochemistry

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“…Labeled precursor studies have shown that both acetate and mevalonate are precursors for isoprenoids in archaea (13,14,33). These observations were supported through archaeal genome analysis which revealed homologs of mevalonate pathway enzymes, including 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) synthase and HMG-CoA reductase (9,20,31).…”

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confidence: 55%

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

2006

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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 reaction. The MJ0044 gene product was found to phosphorylate isopentenyl phosphate, generating isopentenyl diphosphate. Unlike other known kinases associated with isoprene biosynthesis, Methanocaldococcus jannaschii isopentenyl phosphate kinase is predicted to be a member of the aspartokinase superfamily.Isoprenoids are a large family of natural products that includes metabolically and medically important compounds such as cholesterol, steroid hormones, ubiquinone, carotenoids, and taxol. In archaea, isoprenoids are of particular interest because they are the major component of their membrane lipids (22). Archaeal lipids are composed of isoprenoid side chains connected to sn-glycerol-1-phosphate through ether linkages. Thus, the archaeal lipids differ from the majority of eukaryotic and eubacterial lipids in the isoprene nature of the alkyl chain, the stereoconfiguration of the glycerol moiety, and the presence of ether rather than ester linkages (22).Despite the structural diversity seen in this group of compounds, all isoprenoids are derived from two precursor compounds: isopentenyl diphosphate (IPP) and its isomer 3,3-dimethylallyl diphosphate. Two pathways for the biosynthesis of these central metabolites are currently known: the mevalonate and the deoxy-D-xylulose 5-phosphate (DXP) pathways (19). The DXP pathway is known to function in the majority of bacteria and plant plastids, while the mevalonate pathway is typically found in animals, plant cytosol, and archaea. Some bacteria, along with plants, have been shown to operate with both pathways (19).Labeled precursor studies have shown that both acetate and mevalonate are precursors for isoprenoids in archaea (13,14,33). These observations were supported through archaeal genome analysis which revealed homologs of mevalonate pathway enzymes, including 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) synthase and HMG-CoA reductase (9,20,31). Putative genes for other enzymes in the mevalonate pathway, however, were not immediately identified on the basis of sequence similarity. However, two additional enzymes of the pathway, mevalonate kinase and IPP isomerase, were subsequently identified and characterized (4, 17).Although Sulfolobus tokodaii and Sulfolobus solfataricus have homologs for all mevalonate pathway enzymes, genomic analysis was unable to identify genes for phosphomevalonate kinase or diphosphomevalonate decarboxylase in most archaea (7). Similarly, several species of Halobacteria have gene homologs for diphosphomevalonate decarboxylase but not for phosphomevalonate kin...

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“…In methanogens, PYC and PPC activities serve anabolic functions. In Methanococcus, Methanobacterium, and Methanospirillum, oxaloacetate is the starting point of an incomplete reductive tricarboxylic acid cycle that terminates at ␣-ketoglutarate and provides several precursors for cell material and coenzyme biosynthesis (7,(12)(13)(14). In Methanosarcina, oxaloacetate initiates an incomplete oxidative tricarboxylic acid cycle to generate ␣-ketoglutarate (10).…”

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confidence: 99%

Purification, Regulation, and Molecular and Biochemical Characterization of Pyruvate Carboxylase from Methanobacterium thermoautotrophicum Strain ΔH

Mukhopadhyay

Stoddard²,

Wolfe

1998

Journal of Biological Chemistry

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We discovered that Methanobacterium thermoautotrophicum strain ⌬H possessed pyruvate carboxylase (PYC), and this biotin prototroph required exogenously supplied biotin to exhibit detectable amounts of PYC activity. The enzyme was highly labile and was stabilized by 10% inositol in buffers to an extent that allowed purification to homogeneity and characterization. , or Co 2؉ . The 540-kDa enzyme of A 4 B 4 composition contained a non-biotinylated 52-kDa subunit (PYCA) and a 75-kDa biotinylated subunit (PYCB). The pycB gene was probably monocistronic and followed by a putative gene of a DNA-binding protein on the opposite strand. The pycA was about 727 kilobase pairs away from pycB on the chromosome and was probably co-transcribed with the biotin ligase gene (birA). PYCA and PYCB showed substantial sequence identities (33-62%) to, respectively, the biotin carboxylase and biotin carboxyl carrier ؉ carboxyltransferase domains or subunits of known biotin-dependent carboxylases/decarboxylases. We discovered that PYCB and probably the equivalent domains or subunits of all biotin-dependent carboxylases harbored the serine/ threonine dehydratase types of pyridoxal-phosphate attachment site. Our results and the existence of an alternative oxaloacetate synthesizing enzyme phosphoenolpyruvate carboxylase in M. thermoautotrophicum strain ⌬H (Kenealy, W. R., and Zeikus, J. G. (1982) FEMS Microbiol. Lett. 14, 7-10) raise several questions for future investigations.

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Mevalonic acid is partially synthesized from amino acids in Halobacterium cutirubrum: a 13C nuclear magnetic resonance study

Cited by 36 publications

References 19 publications

Biosynthesis of the 1,3,4,6-hexanetetracarboxylic acid subunit of methanofuran

Biosynthesis of the 1,3,4,6-hexanetetracarboxylic acid subunit of methanofuran

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

Purification, Regulation, and Molecular and Biochemical Characterization of Pyruvate Carboxylase from Methanobacterium thermoautotrophicum Strain ΔH

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