Synthesis of the unusual lipid bis(monoacylglycero)phosphate in environmental bacteria

Abstract

Summary The bacterial membrane is constantly remodelled in response to environmental conditions and the external supply of precursor molecules. Some bacteria are able to acquire exogenous lyso‐phospholipids and convert them to the corresponding phospholipids. Here, we report that some soil‐dwelling bacteria have alternative options to metabolize lyso‐phosphatidylglycerol (L‐PG). We find that the plant‐pathogen Agrobacterium tumefaciens takes up this mono‐acylated phospholipid and converts it to two distinct isoforms of the non‐canonical lipid bis(monoacylglycero)phosphate (BMP). Chromatographic separation and quadrupole‐time‐of‐flight MS/MS analysis revealed the presence of two possible BMP stereo configurations acylated at either of the free hydroxyl groups of the glycerol head group. BMP accumulated in the inner membrane and did not visibly alter cell morphology and growth behaviour. The plant‐associated bacterium Sinorhizobium meliloti was also able to convert externally provided L‐PG to BMP. Other bacteria like Pseudomonas fluorescens and Escherichia coli metabolized L‐PG after cell disruption, suggesting that BMP production in the natural habitat relies both on dedicated uptake systems and on head‐group acylation enzymes. Overall, our study adds two previously overlooked phospholipids to the repertoire of bacterial membrane lipids and provides evidence for the remarkable condition‐responsive adaptation of bacterial membranes.

Chiral analysis of glycerol phosphates - can bacteria biosynthesize heterochiral phospholipid membranes?

“…In the next step of the analysis, the HILIC fraction (i.e., PG manually collected in the separation time range of 17.6 -18.4 min) was hydrolyzed with phospholipase C. The obtained 1,2-diacyl-sn-glycerols were immediately derivatized to AcTAGs to prevent acyl migration during subsequent separation processes. Based on our analysis of FAMEs and the published data [47,48] see above, it could be assumed that the most molecular species will contain branched fatty acids. Therefore, gradient elution was used for RP-HPLC analysis.…”

“…BMPs represent a different structural variation of PGs in the sn position of fatty acid chains. While PGs have acyls in position sn-1, sn-2, then BMPs have acyls in the sn-1, sn-1' position [47]. Since PGs and BMPs have the same sum formula, they cannot be distinguished by MS level.…”

The Batten disease gene product CLN5 is the lysosomal bis(monoacylglycero)phosphate synthase

“…Our study elucidates BMP biosynthesis and reveals an anabolic function of late endosomes/lysosomes. B is(monoacylglycero)phosphate (BMP), also known as lysobisphosphatidic acid, is conserved from bacteria to most eukaryotes (1,2). BMP is an anionic, late endosome/lysosome (LE/LY)-specific glycerophospholipid with unusual esterification, unsaturation, and stereochemistry.…”