Identification of a protein responsible for the synthesis of archaeal membrane-spanning GDGT lipids

Abstract

Glycerol dibiphytanyl glycerol tetraethers (GDGTs) are archaeal monolayer membrane lipids that can provide a competitive advantage in extreme environments. Here, we identify a radical SAM protein, tetraether synthase (Tes), that participates in the synthesis of GDGTs. Attempts to generate a tes-deleted mutant in Sulfolobus acidocaldarius were unsuccessful, suggesting that the gene is essential in this organism. Heterologous expression of tes homologues leads to production of GDGT and structurally related lipids in the methanogen Methanococcus maripaludis (which otherwise does not synthesize GDGTs and lacks a tes homolog, but produces a putative GDGT precursor, archaeol). Tes homologues are encoded in the genomes of many archaea, as well as in some bacteria, in which they might be involved in the synthesis of bacterial branched glycerol dialkyl glycerol tetraethers.

Disentangling the lipid divide: Identification of key enzymes for the biosynthesis of unusual Membrane-spanning and Ether lipids in Bacteria

“…The anticipated biochemical mechanism for MSL synthesis is based on the dimerization of the FA building blocks through the formation of a carbon-carbon bond between either the ω -1 carbon of C 16 FAs or the ω carbon of iso -C 15:0 FAs to form DA or iso -DA, respectively 8,1 . A radical reaction mechanism for the formation of MSLs in bacteria has been previously proposed 27 , and recently confirmed for the synthesis of the isoprenoid MSLs in Archaea 9 . This reaction would involve a radical intermediate formed by a hydrogen extraction at the tail of one of the fatty acids, followed by a condensation with the other tail, involving the loss of another hydrogen, resulting in the formation of a C-C bond in the absence of an activated intermediate.…”

“…In the same way, iso -DAs are believed to be produced by the condensation of two iso -C 15:0 FAs at the ω positions 1 , but the enzymes responsible for the formation of these types of bacterial MSLs (i.e., MSL synthases) remain elusive. A recent study has identified a radical SAM enzyme (tetraether synthase, Tes) responsible for the archaeal tail-to-tail coupling of two ether-bound phytanyl chains, enabling the synthesis of glycerol dialkyl glycerol tetraethers (GDGTs) 9 . Since Tes homologs were detected in bacterial genomes, they have been hypothesized to be involved in the synthesis of bacterial MSLs 9 .…”

“…These homologs of the bacterial MSL synthase could potentially be able to connect the tails of two isoprenoid chains since this is reaction is somewhat similar to the one connecting two FAs for the production of bacterial MSLs. However, the genomes of these archaeal species also harbor homologs of Tes 9 . Furthermore, the low homology with the confirmed bacterial MSL synthase, and the apparent limited archaeal distribution of the MSL synthase homologs argues against the canonical coupling of isoprenoids by MSL synthase in archaea.…”

The production of diverse brGDGTs by an Acidobacterium allows a direct test of temperature and pH controls on their distribution

“…Recently, tetraether synthase (Tes), a key protein responsible for the formation of archaeal isoprenoid GDGTs (isoGDGTs) via the combination of two archaeol molecules, has been identified (21). Bacterial brGDGTs bear a structural resemblance to archaeal isoGDGTs, i.e., both of them consisting of two alkyl chains linked to two glycerol backbones via four ether bonds (15).…”

“…Bacterial brGDGTs bear a structural resemblance to archaeal isoGDGTs, i.e., both of them consisting of two alkyl chains linked to two glycerol backbones via four ether bonds (15). The Tes protein could, therefore, also be involved in the biosynthesis of bacterial brGDGTs, since Tes homologs have been found in bacterial genomes of diverse phyla including Acidobacteria (21).…”