A sustainable and regioselective synthesis of Hemi-bis(monoacylglycero)phosphates and bis(diacylglycero)phosphates

A sustainable and green approach was developed for the scalable synthesis of uncommon naturally occurring phospholipid species, Hemi-bis(monoacylglycero) phosphates (Hemi-BMPs) and bis(diacylglycero)phosphates (BDPs) via the phospholipase D (PLD) mediated transphosphatidylation. PLD from Streptomyces sp. showed great substrate promiscuity for both phospholipids from different biological sources, and alcohol donors with diverse regiochemistry; monoacylglycerols with diverse fatty acyl structures (C12-C22), affording 74-92 wt% yields in 2 h. Experimental results demonstrated that the reaction rate is rather independent of phosphatidyls but to a large extent governed by the size, shape and regiolocation of fatty acyls incorporated on the glycerol backbone, particularly for the regio-isomers of bulky diacylglycerols (Sn-1,3 or Sn-1,2), which displays great diversity. In addition, a plausible mechanism is proposed based on molecular simulations for an elaborated explanation of the reaction thermodynamic and kinetic favorability toward the synthesis of Hemi-BMPs and BDPs.

Automated summary

A sustainable and green synthesis of Hemi-BMPs and BDPs, uncommon naturally occurring phospholipids, was achieved via phospholipase D (PLD) mediated transphosphatidylation. The enzyme from Streptomyces sp. exhibited excellent substrate promiscuity for phospholipids from different sources and alcohol donors with diverse structures, leading to high yields in a short reaction time. The reaction rate was found to be dependent on the size, shape, and regiolocation of fatty acyls on the glycerol backbone, especially for bulky diacylglycerol regio-isomers.