Biosynthesis of GMGT Lipids by a Radical SAM Enzyme Associated with Anaerobic Archaea and Oxygen-Deficient Environments.

Archaea possess characteristic membrane-spanning lipids that are thought to contribute to the adaptation to extreme environments. However, the biosynthesis of these lipids is poorly understood. Here, we identify a radical S-adenosyl-L-methionine (SAM) enzyme that synthesizes glycerol monoalkyl glycerol tetraethers (GMGTs). The enzyme, which we name GMGT synthase (Gms), catalyzes the formation of a C(sp3)-C(sp3) linkage between the two isoprenoid chains of glycerol dialkyl glycerol tetraethers (GDGTs). This conclusion is supported by heterologous expression of gene gms from a GMGT-producing species in a methanogen, as well as demonstration of in vitro activity using purified Gms enzyme. Additionally, we show that genes encoding putative Gms homologs are present in obligate anaerobic archaea and in metagenomes obtained from oxygen-deficient environments, and appear to be absent in metagenomes from oxic settings. The biosynthesis of membrane-spanning lipids in archaea is poorly understood. Here, Li et al. identify an archaeal enzyme that forms a C(sp3)-C(sp3) linkage between isoprenoid chains for the synthesis of membrane-spanning GMGT lipids, and show that the corresponding gene is exclusively found in obligate anaerobic archaea and in metagenomes from oxygen-deficient environments.