Publications

• Identification of CDP-archaeol synthase, a missing link of ether lipid biosynthesis in Archaea.

  Jain S., Caforio A., Fodran P., Lolkema J.S., Minnaard A.J., Driessen A.J.

  Archaeal membrane lipid composition is distinct from Bacteria and Eukarya, consisting of isoprenoid chains etherified to the glycerol carbons. Biosynthesis of these lipids is poorly understood. Here we identify and characterize the archaeal membrane protein CDP-archaeol synthase (CarS) that cataly ... >> More

  Archaeal membrane lipid composition is distinct from Bacteria and Eukarya, consisting of isoprenoid chains etherified to the glycerol carbons. Biosynthesis of these lipids is poorly understood. Here we identify and characterize the archaeal membrane protein CDP-archaeol synthase (CarS) that catalyzes the transfer of the nucleotide to its specific archaeal lipid substrate, leading to the formation of a CDP-activated precursor (CDP-archaeol) to which polar head groups are attached. The discovery of CarS enabled reconstitution of the entire archaeal lipid biosynthesis pathway in vitro, starting from simple isoprenoid building blocks and using a set of five purified enzymes. The cell free synthetic strategy for archaeal lipids we describe opens opportunity for studies of archaeal lipid biochemistry. Additionally, insights into archaeal lipid biosynthesis reported here allow addressing the evolutionary hypothesis of the lipid divide between Archaea and Bacteria. << Less

  Chem. Biol. 21:1392-1401(2014) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.

• CTP:2,3-di-O-geranylgeranyl-sn-glycero-1-phosphate cytidyltransferase in the methanogenic archaeon Methanothermobacter thermoautotrophicus.

  Morii H., Nishihara M., Koga Y.

  CDP-2,3-di-O-geranylgeranyl-sn-glycerol synthase (CDP-archaeol synthase) activity was discovered in the membrane fraction of the methanoarchaeon Methanothermobacter thermoautotrophicus cells. It catalyzed the formation of CDP-2,3-di-O-geranylgeranyl-sn-glycerol from CTP and 2,3-di-O-geranylgeranyl ... >> More

  CDP-2,3-di-O-geranylgeranyl-sn-glycerol synthase (CDP-archaeol synthase) activity was discovered in the membrane fraction of the methanoarchaeon Methanothermobacter thermoautotrophicus cells. It catalyzed the formation of CDP-2,3-di-O-geranylgeranyl-sn-glycerol from CTP and 2,3-di-O-geranylgeranyl-sn-glycero-1-phosphate (unsaturated archaetidic acid). The identity of the reaction product was confirmed by thin layer chromatography, fast atom bombardment-mass spectroscopy, chemical analysis, and by UV spectroscopy. One mole of the product was formed from approximately 1 mol of each of the reactants. The enzyme showed maximal activity at pH 8.5 and 55 degrees C in the presence of Mg(2+) and K(+) ions. By in vivo pulse labeling of phospholipids with (32)P(i), CDP-archaeol was found to be an intracellular intermediate. A cell-free homogenate of M. thermoautotrophicus, when incubated with l-serine, converted the product of CDP-archaeol synthase reaction to a product with the same chromatographic mobility as archaetidylserine. It was concluded from these results that both CDP-archaeol and CDP-archaeol synthase were involved in cellular phospholipid biosynthesis. Among various synthetic substrate analogs, both enantiomers of unsaturated archaetidic acid possessing geranylgeranyl chains showed similar levels of activity, while archaetidic acid with saturated or monounsaturated isoprenoid or straight chains was a poor substrate, despite having the same stereostructure as the fully active substrate. The ester analogs with geranylgeranioyl chains showed significant activities. These results suggest that the enzyme dose not recognize ether or ester bonds between glycerophosphate and hydrocarbon chains nor the stereostructure of the glycerophosphate backbone but mainly targets substrates with geranylgeranyl chains. << Less

  J Biol Chem 275:36568-36574(2000) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.

• (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.

  Hemmi H., Shibuya K., Takahashi Y., Nakayama T., Nishino T.

  The core structure of membrane lipids of archaea have some unique properties that permit archaea to be distinguished from the others, i.e. bacteria and eukaryotes. (S)-2,3-Di-O-geranylgeranylglyceryl phosphate synthase, which catalyzes the transfer of a geranylgeranyl group from geranylgeranyl dip ... >> More

  The core structure of membrane lipids of archaea have some unique properties that permit archaea to be distinguished from the others, i.e. bacteria and eukaryotes. (S)-2,3-Di-O-geranylgeranylglyceryl phosphate synthase, which catalyzes the transfer of a geranylgeranyl group from geranylgeranyl diphosphate to (S)-3-O-geranylgeranylglyceryl phosphate, is involved in the biosynthesis of archaeal membrane lipids. Enzymes of the UbiA prenyltransferase family are known to catalyze the transfer of a prenyl group to various acceptors with hydrophobic ring structures in the biosynthesis of respiratory quinones, hemes, chlorophylls, vitamin E, and shikonin. The thermoacidophilic archaeon Sulfolobus solfataricus was found to encode three homologues of UbiA prenyltransferase in its genome. One of the homologues encoded by SSO0583 was expressed in Escherichia coli, purified, and characterized. Radio-assay and mass spectrometry analysis data indicated that the enzyme specifically catalyzes the biosynthesis of (S)-2,3-di-O-geranylgeranylglyceryl phosphate. The fact that the orthologues of the enzyme are encoded in almost all archaeal genomes clearly indicates the importance of their functions. A phylogenetic tree constructed using the amino acid sequences of some typical members of the UbiA prenyltransferase family and their homologues from S. solfataricus suggests that the two other S. solfataricus homologues, excluding the (S)-2,3-di-O-geranylgeranylglyceryl phosphate synthase, are involved in the production of respiratory quinone and heme, respectively. We propose here that archaeal prenyltransferases involved in membrane lipid biosynthesis might be prototypes of the protein family and that archaea might have played an important role in the molecular evolution of prenyltransferases. << Less

  J. Biol. Chem. 279:50197-50203(2004) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.