Serinophospholipids: A third type of natural phospholipid discovered in a thermophilic bacterium

Phospholipids are an essential constituent of cells with all life thought to produce phospholipids with either a glycerol or sphingoid moiety at their core. For the first time, we demonstrate that a thermophilic bacterium, Limisphaera ngatamarikiensis NGM72.4T, produces a third type of phospholipid – serinophospholipids – which are distinct from glycero- and sphingophospholipids by featuring a serinol backbone instead. We show that the major serinophospholipid metabolites are N,O-diacylserinophospho-N-methylethanolamine and N,O-diacylserinophosphoethanolamine, and that serinophospholipids constitute up to 38% of the phospholipid mass. Furthermore, we demonstrate that these metabolites are further differentiated from ‘traditional’ bacterial glycerophospholipids by their backbone stereochemistry. In contrast to bacterial glycerophospholipids, which have an sn-glycerol-3-phosphate (G3P) architecture, the newly discovered serinophospholipids have an (S)-configured serinol core that is equivalent to the sn-glycerol-1-phosphate (G1P) arrangement characteristic of Archaea. This research expands the known diversity of phospholipids beyond the current two backbone paradigm and challenges our understanding of lipid evolution.