Bacterial tetraether lipid biosynthesis links membrane adaption to paleoclimate proxies

Vivien Schneider , Catherine Fontana, Adam D. Younkin, Ashley J. Winter, Felix J. Elling, Sebastian H. Kopf, B. David A. Naafs

Membrane-spanning tetraether lipids are best known as an adaptive mechanism of archaea for stabilizing their membranes under extreme conditions. Bacteria typically rely on bilayer-forming phospholipids, making the occurrence of membrane-spanning branched glycerol dialkyl glycerol tetraethers (brGDGTs) in some bacteria highly unusual. BrGDGTs occur globally in soils and sediments and exhibit systematic structural changes (degree of methylation) with temperature, forming the basis of widely used paleoclimate proxies. However, their biosynthetic pathway has remained largely unresolved. Here, we conducted isotope-labeling experiments with Solibacter usitatus to elucidate brGDGT biosynthesis. Our results demonstrate that L-Leucine supplies the iso-branched building blocks of brGDGT alkyl chains via isoC15:0 fatty acids and isoC15:0 dialkyl glycerol diether intermediates, and that L-methionine provides the methyl group for additional chain methylation, with a labeling pattern implicating a class B radical S-adenosylmethionine methyltransferase. These findings establish a mechanistic understanding for bacterial tetraether biosynthesis that underpins paleoclimate proxies and reveal how bacteria modify membrane lipids, showing similarities across the Domains of Life.