Ornithine lipids and other acyloxyacyl amino lipids: the coming-of-age story of a group of non-canonical membrane lipids.

Ornithine lipids (OLs) are phosphorus-free membrane lipids present in many bacteria, but absent from eukaryotes and archaea. Three pathways for OL synthesis have been reported to date. Conditions that induce OL synthesis include elevated temperature, low pH, low phosphate concentration, and low salt concentration. OLs can be modified by different hydroxylations, N-methylation, or taurine transfer. These modifications can be expected to alter the biophysical properties of individual lipid molecules and the membrane as a whole, with potential applications in synthetic biology. The presence and synthesis of OLs are frequently associated with increased stress resistance, and bacterial mutants of some species deficient in OL synthesis show increased susceptibility to elevated temperatures or reduced pH. OLs have been shown to be important for bacteria-host interactions and, recently, to interact with Toll-like receptor 4 (TLR4). We present a comprehensive analysis of the taxonomic distribution of genes encoding putative OL synthases, enabling predictions of which bacteria are expected to have the capacity to synthesize OL at least under specific growth conditions. Lipids structurally analogous to OLs in which other amino acids replace ornithine have also been described and are synthesized by enzymes homologous to OL synthases. In recent years, a wide range of studies and observations related to OLs have been published, including the identification of genes encoding novel OL synthases, novel OL-modifying enzymes, and novel OL structures; the sensing of OLs and other aminolipids by eukaryotic organisms; and their possible use in synthetic biology. In the present review, we discuss these recent advances. KEY POINTS: Ornithine lipids are phosphorus-free membrane lipids present in a wide range of bacteria. The presence and induction of OLs are associated with increased stress resistance. The presence and modification of OLs affect the membrane properties of E. coli cells.