Phylogenomic investigation of phospholipid synthesis in archaea

Abstract

Archaea have idiosyncratic cell membranes usually based on phospholipids containing glycerol-1-phosphate linked by ether bonds to isoprenoid lateral chains. Since these phospholipids strongly differ from those of bacteria and eukaryotes, the origin of the archaeal membranes (and by extension, of all cellular membranes) was enigmatic and called for accurate evolutionary studies. In this paper we review some recent phylogenomic studies that have revealed a modified mevalonate pathway for the synthesis of isoprenoid precursors in archaea and suggested that this domain uses an atypical pathway of synthesis of fatty acids devoid of any acyl carrier protein, which is essential for this activity in bacteria and eukaryotes. In addition, we show new or updated phylogenetic analyses of enzymes likely responsible for the isoprenoid chain synthesis from their precursors and the phospholipid synthesis from glycerol phosphate, isoprenoids, and polar head groups. These results support that most of these enzymes can be traced back to the last archaeal common ancestor and, in many cases, even to the last common ancestor of all living organisms.

Figure 1

Biosynthesis pathways of phospholipid components in archaea. Abbreviations for the archaeal mevalonate (MVA) pathway: AACT, acetoacetyl-CoA thiolase; HMGS, 3-hydroxy-3-methylglutaryl-CoA synthase; HMGR, 3-hydroxy-3-methylglutaryl-CoA reductase; MVK, mevalonate kinase; IPK, isopentenyl phosphate kinase; IDI2, isopentenyl diphosphate isomerase type II. GHMP, galactokinase-homoserine kinase-mevalonate kinase-phosphomevalonate kinase; IPPS, isoprenyl diphosphate synthases (asterisks indicate enzymes shared with the eukaryotic MVA pathway). Abbreviations for the hypothetical archaeal fatty acid (FA) synthesis pathway: ACC, acetyl-CoA carboxylase; PCC, propionyl-CoA carboxylase; KR-PhaB, beta-ketoacyl reductase; DH-MaoC/PhaJ, beta-hydroxyacyl dehydratase; ER, enoyl reductase; SDR, short-chain dehydrogenases/reductases. Abbreviations for the sn-glycerol-1-phosphate synthesis pathway: G1PDH, glycerol-1-phosphate dehydrogenase; DHQS, 3-dehydroquinate synthase; GDH, glycerol dehydrogenase; ADH, alcohol dehydrogenase. Abbreviations for the phospholipid assembly pathway: GGGPS, (S)-3-O-geranylgeranylglyceryl phosphate synthase; DGGGPS, (S)-2,3-di-O-geranylgeranylglyceryl phosphate synthase; GGR, geranylgeranyl reductase; CDSA, CDP diglyceride synthetase. (^#) points to the ability of GGRs to reduce isoprenoids at different steps in the biosynthesis pathway. Names between parentheses indicate the family or superfamily to which belong the archaeal enzymes postulated to carry out particular functions on the basis of phylogenomic analyses.

Figure 2

Short-chain IPPS phylogenetic tree reconstructed using 136 representative sequences and 244 conserved sites. Multifurcations correspond to branches with support values <0.50. Triangles correspond to well supported-bacterial clades (numbers in parentheses correspond to the number of sequences included in these clades). For the complete phylogeny, see Supplementary Figure 1.

Figure 3

Long-chain IPPS phylogenetic tree reconstructed using 218 representative sequences and 241 conserved sites. Multifurcations correspond to branches with support values <0.50. Triangles correspond to well-supported clades outside Archaea (numbers in parentheses correspond to the number of sequences included in these clades). For the complete phylogeny, see Supplementary Figure 2.

Figure 4

CdsA phylogenetic tree reconstructed using 133 representative sequences and 87 conserved sites. Branches with support values <0.50 have been collapsed. For the complete phylogeny, see Supplementary Figure 8.