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MetaCyc Pathway: CDP-archaeol biosynthesis

Enzyme View:

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Biosynthesis Fatty Acids and Lipids Biosynthesis Phospholipid Biosynthesis

Some taxa known to possess this pathway include ? : Archaeoglobus fulgidus , Methanothermobacter marburgensis , Methanothermobacter thermautotrophicus , Methanothermobacter thermautotrophicus Delta H

Expected Taxonomic Range: Archaea

Summary:
General Background

One of the most striking physiological differences between the archaea and other organisms is the structure of their membrane lipids. The most exclusive feature of archaeal phospholipids is their sn-glycerol 1-phosphate backbone, which is an enantiomer of the sn-glycerol 3-phosphate used by bacteria and eukaryotic organisms. It has been suggested that archaea and bacteria were differentiated by the occurrence of cells enclosed by membranes of phospholipids with sn-glycerol 1-phosphate and sn-glycerol 3-phosphate as a backbone, respectively [Koga98].

Other features that are unique to archaeal phospholipids include side chains that are derivatives of isoprenoid alcohols rather than fatty acids, which are linked by ether linkages (rather than ester linkages) to the glycerophosphate backbone [Kates78]. The isoprenoids are usually modified by saturation of the double bonds - a modification that is believed to increase the ability of the lipids to survive the extreme conditions that archaea often face. Another unique feature is the occurrence of bipolar lipids with a tetraether core, which are present in significant numbers in archaeal species.

In contrast to these differences, most of the polar head groups of archaeal phospholipids are similar to those found in the other kingdoms - ethanolamine, L-serine, glycerol, myo-inositol and choline [Koga07].

The major polar lipids of the archaeon Methanothermobacter thermautotrophicus are L-serine, ethanolamine, or myo-inositol-containing di- and tetraether type phospholipids and phosphoglycolipids, and gentiobiose-containing di- and tetraether type glycolipids. Examples of non-glycosylated lipids include archaetidylserine, archaetidylethanolamine, archaetidylinositol and archaetidylglycerol.

About This Pathway

CDP-archaeol, either in its unsaturated form or its saturated form, is expected to be the common precursor of biosynthesis of all the archaeal phospholipids, analogous to CDP-diacylglycerol in bacteria. The pathway leading to the synthesis of CDP-archaeol has been partially characterized in the organisms Methanothermobacter thermautotrophicus and Methanothermobacter marburgensis. The four enzymes catalyzing the steps leading to CDP-archaeol have been studied in vitro and are well characterized [Nishihara95, Chen93, Morii00, Morii03]. A large part of this pathway (up to 2,3-bis-O-(geranylgeranyl)glycerol 1-phosphate) has been reconstructed in Escherichia coli using cloned genes from Archaeoglobus fulgidus [Lai09].

The pathway starts with the reduction of dihydroxyacetone phosphate, an intermediate of glycolysis, to sn-glycerol 1-phosphate by the enzyme , G-1-P dehydrogenase. Activity of this enzyme or presence of the the genes encoding it have been detected in all archaeal species studied so far [Nishihara99]. In the next two steps, two molecules of geranylgeranyl diphosphate are bound to the sn-glycerol 1-phosphate backbone through two ether bonds at the sn-2 and -3 positions. The product of these additions is 2,3-bis-O-(geranylgeranyl)glycerol 1-phosphate (unsaturated archaetidate). This intermediate can be reduced to 2,3-bis-O-phytanyl-sn-glycerol 1-phosphate (saturated archaetidate) by the enzyme 2,3-di-O-geranylgeranyl-sn-glycerol 1-phosphate reductase. Either form of archaetidate can be activated by CTP (catalyzed by CDP-archaeol synthase) to form the corresponding form of CDP-archaeol, which is modified by different enzymes to form the final lipids, as described in archaetidylinositol biosynthesis and archaetidylserine and archaetidylethanolamine biosynthesis.

This pathway is analogous to the bacterial pathway of CDP-diacylglycerol Biosynthesis, from which it differs in the use of sn-glycerol 1-phosphate, the formation of ether bonds, and the nature of the hydrocarbon chains.

Superpathways: Methanobacterium thermoautotrophicum biosynthetic metabolism , archaetidylserine and archaetidylethanolamine biosynthesis , archaetidylinositol biosynthesis

Credits:
Created 08-Oct-2009 by Caspi R , SRI International
Revised 26-Mar-2013 by Caspi R , SRI International


References

Chen93: Chen A, Zhang D, Poulter CD (1993). "(S)-geranylgeranylglyceryl phosphate synthase. Purification and characterization of the first pathway-specific enzyme in archaebacterial membrane lipid biosynthesis." J Biol Chem 268(29);21701-5. PMID: 8408023

Kates78: Kates M (1978). "The phytanyl ether-linked polar lipids and isoprenoid neutral lipids of extremely halophilic bacteria." Prog Chem Fats Other Lipids 15(4);301-42. PMID: 358256

Koga07: Koga Y, Morii H (2007). "Biosynthesis of ether-type polar lipids in archaea and evolutionary considerations." Microbiol Mol Biol Rev 71(1);97-120. PMID: 17347520

Koga98: Koga Y, Kyuragi T, Nishihara M, Sone N (1998). "Did archaeal and bacterial cells arise independently from noncellular precursors? A hypothesis stating that the advent of membrane phospholipid with enantiomeric glycerophosphate backbones caused the separation of the two lines of descent." J Mol Evol 46(1);54-63. PMID: 9419225

Lai09: Lai D, Lluncor B, Schroder I, Gunsalus RP, Liao JC, Monbouquette HG (2009). "Reconstruction of the archaeal isoprenoid ether lipid biosynthesis pathway in Escherichia coli through digeranylgeranylglyceryl phosphate." Metab Eng. PMID: 19558961

Morii00: Morii H, Nishihara M, Koga Y (2000). "CTP:2,3-di-O-geranylgeranyl-sn-glycero-1-phosphate cytidyltransferase in the methanogenic archaeon Methanothermobacter thermoautotrophicus." J Biol Chem 275(47);36568-74. PMID: 10960477

Morii03: Morii H, Koga Y (2003). "CDP-2,3-Di-O-geranylgeranyl-sn-glycerol:L-serine O-archaetidyltransferase (archaetidylserine synthase) in the methanogenic archaeon Methanothermobacter thermautotrophicus." J Bacteriol 185(4);1181-9. PMID: 12562787

Nishihara95: Nishihara M, Koga Y (1995). "sn-glycerol-1-phosphate dehydrogenase in Methanobacterium thermoautotrophicum: key enzyme in biosynthesis of the enantiomeric glycerophosphate backbone of ether phospholipids of archaebacteria." J Biochem 117(5);933-5. PMID: 8586635

Nishihara99: Nishihara M, Yamazaki T, Oshima T, Koga Y (1999). "sn-glycerol-1-phosphate-forming activities in Archaea: separation of archaeal phospholipid biosynthesis and glycerol catabolism by glycerophosphate enantiomers." J Bacteriol 181(4);1330-3. PMID: 9973362

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Daiyasu02: Daiyasu H, Hiroike T, Koga Y, Toh H (2002). "Analysis of membrane stereochemistry with homology modeling of sn-glycerol-1-phosphate dehydrogenase." Protein Eng 15(12);987-95. PMID: 12601138

Hemmi04: Hemmi H, Shibuya K, Takahashi Y, Nakayama T, Nishino T (2004). "(S)-2,3-Di-O-geranylgeranylglyceryl phosphate synthase from the thermoacidophilic archaeon Sulfolobus solfataricus. Molecular cloning and characterization of a membrane-intrinsic prenyltransferase involved in the biosynthesis of archaeal ether-linked membrane lipids." J Biol Chem 279(48);50197-203. PMID: 15356000

Koga03: Koga Y, Sone N, Noguchi S, Morii H (2003). "Transfer of pro-R hydrogen from NADH to dihydroxyacetonephosphate by sn-glycerol-1-phosphate dehydrogenase from the archaeon Methanothermobacter thermautotrophicus." Biosci Biotechnol Biochem 67(7);1605-8. PMID: 12913312

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Murakami07: Murakami M, Shibuya K, Nakayama T, Nishino T, Yoshimura T, Hemmi H (2007). "Geranylgeranyl reductase involved in the biosynthesis of archaeal membrane lipids in the hyperthermophilic archaeon Archaeoglobus fulgidus." FEBS J 274(3);805-14. PMID: 17288560

Nishihara97: Nishihara M, Koga Y (1997). "Purification and properties of sn-glycerol-1-phosphate dehydrogenase from Methanobacterium thermoautotrophicum: characterization of the biosynthetic enzyme for the enantiomeric glycerophosphate backbone of ether polar lipids of Archaea." J Biochem 122(3);572-6. PMID: 9348086

Nishimura06: Nishimura Y, Eguchi T (2006). "Biosynthesis of archaeal membrane lipids: digeranylgeranylglycerophospholipid reductase of the thermoacidophilic archaeon Thermoplasma acidophilum." J Biochem 139(6);1073-81. PMID: 16788058

Soderberg01: Soderberg T, Chen A, Poulter CD (2001). "Geranylgeranylglyceryl phosphate synthase. Characterization of the recombinant enzyme from Methanobacterium thermoautotrophicum." Biochemistry 40(49);14847-54. PMID: 11732904

Yokoi12: Yokoi T, Isobe K, Yoshimura T, Hemmi H (2012). "Archaeal phospholipid biosynthetic pathway reconstructed in Escherichia coli." Archaea 2012;438931. PMID: 22645416

Zhang90: Zhang, D. L., Daniels, L., Poulter, C.D. (1990). "Biosynthesis of archaebacterial membranes. Formation of isoprene ethers by a prenyl transfer reaction." J. Am. Chem. Soc. 112: 1264-1265.


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Wed Nov 26, 2014, biocyc13.