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

TY - JOUR

T1 - A sustainable and regioselective synthesis of Hemi-bis(monoacylglycero)phosphates and bis(diacylglycero)phosphates

AU - Bogojevic, Oliver

AU - Zhang, Yan

AU - Daugaard Wolff, Christian

AU - Nygaard, Jens Vinge

AU - Wiking, Lars

AU - Arevång, Carl

AU - Guo, Zheng

PY - 2023/7

Y1 - 2023/7

N2 - 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.

AB - 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.

KW - Biocatalysis

KW - Biochemistry

U2 - 10.1016/j.isci.2023.107075

DO - 10.1016/j.isci.2023.107075

M3 - Journal article

C2 - 37448559

SN - 2589-0042

VL - 26

JO - iScience

JF - iScience

IS - 7

M1 - 107075

ER -