A re-evaluation of the archaeal membrane lipid biosynthetic pathway

• Published in: Nature reviews. Microbiology 2014-06, Vol.12 (6), p.438-448
• Main Authors: Villanueva, Laura, Damsté, Jaap S. Sinninghe, Schouten, Stefan
• Format: Article
• Language: English
• Subjects: 631/114/663/2009; 631/326/26; 631/326/26/2527; 631/45; Amino Acid Sequence; Amino acids; Ammonia; analysis; Archaea; Archaea - cytology; Archaea - physiology; Archaeabacteria; Archaeal Proteins - chemistry; Archaeal Proteins - genetics; Archaeal Proteins - metabolism; Bacteria; Biosynthesis; Cell Membrane - physiology; Enzymes; Gene Expression Regulation, Archaeal - physiology; Glycerin; Glycerol; Infectious Diseases; Life Sciences; Lipids; Medical Microbiology; Membrane lipids; Membrane Lipids - biosynthesis; Membrane Lipids - chemistry; Membranes; Microbiological synthesis; Microbiology; Molecular Sequence Data; Molecular Structure; Parasitology; Physiological aspects; Sulfur; Virology
• ISSN: 1740-1526; 1740-1534
• DOI: 10.1038/nrmicro3260

Key Points Archaea were initially thought to be confined to extreme environments, but they are now known to occur ubiquitously in nature and to be important players in global biogeochemical cycles. Archaea are characterized by their unique membrane lipids, which contain isoprene units that are linked to the glycerol backbone by ether bonds (archaeol; C 20 ) in a bilayer and glycerol dialkyl glycerol tetraether (GDGT; C 40 ) in a monolayer. Comparison of the phylogenetic composition of Archaea with the distribution of membrane ether lipids shows that most lipids are not specific for a certain phylogenetic group. Only the GDGT crenarchaeol, which contains four cyclopentane moieties and a cyclohexane moiety, is considered to be characteristic of the Thaumarchaeota, which suggests that the biosynthesis of the cyclohexane moiety is unique to this phylum. The current conception of the archaeal membrane ether lipid biosynthetic pathway involves the condensation of units of isopentenyl diphosphate to form geranylgeranyl diphosphate (GGPP; C 20 ) by a GGPP synthase. The formation of the two ether bonds is catalysed by the geranylgeranylglyceryl phosphate (GGGP) synthase and the digeranylgeranylglyceryl phosphate (DGGGP) synthase. The formation of GDGTs is thought to involve a head-to-head coupling between the two archaeol lipids, followed by internal cyclization to form cyclopentane moieties. These reactions are highly unusual and the enzymes that are involved are unknown. The analysis of the amino acid sequence of most of the archaeal GGGP synthases suggests that they could accommodate substrates >C 20 that already have rings present. The synthesis of the unique cyclohexane moiety-containing GDGT crenarchaeol by Thaumarchaeota might explain the inability to annotate DGGGP synthases in thaumarchaeotal genomes, as a currently unknown, highly divergent DGGGP synthase would be required to accommodate the isoprenyl chain containing the 'bulky' cyclohexane moiety. An alternative archaeal lipid biosynthetic pathway pathway is presented, which is based on a 'multiple-key, multiple-lock' mechanism for which multiple keys with different configurations (owing to the presence of rings) would need to accommodate and specifically interact at the molecular level with different locks (isoprenylglyceryl phosphate synthase and di-isoprenylglyceryl phosphate synthase). This pathway is consistent with most of the phylogenetic relationships that were observed in our study as well as w