Total synthesis of geranylgeranylglyceryl phosphate enantiomers: substrates for characterization of 2,3-O-digeranylgeranylglyceryl phosphate synthase.
To determine the enantioselectivity of (S)-2,3-di-O-geranylgeranylglyceryl phosphate synthase (DGGGPS) from the thermoacidophilic archaeon Sulfolobus solfataricus, we developed an efficient enantioselective route to the enantiomeric geranylgeranylglyceryl phosphates (R)-GGGP and (S)-GGGP. Previous routes to these substrates involved enzymatic conversions due to the lability of the polyprenyl chains toward common phosphorylation reaction conditions. The synthesis described herein employs a mild trimethyl phosphite/carbon tetrabromide oxidative phosphorylation to circumvent this problem. In contrast to previous results suggesting that only (S)-GGGP can act as the prenyl acceptor substrate, both (R)-GGGP and (S)-GGGP were found to be substrates for DGGGPS.
Zhang
Honglu
H
Department of Medicinal Chemistry, The University of Utah, 419 Wakara Way, Suite 205, Salt Lake City, Utah 84108-1257, USA.
Shibuya
Kyohei
K
Hemmi
Hisashi
H
Nishino
Tokuzo
T
Prestwich
Glenn D
GD
D004122:Dimethylallyltranstransferase / Q000378:metabolism*; D005994:Glycerophosphates / Q000138:chemical synthesis* / Q000737:chemistry; D008563:Membrane Lipids / Q000096:biosynthesis* / Q000737:chemistry; D015394:Molecular Structure; D011106:Polyisoprenyl Phosphates / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D048229:Sulfolobus solfataricus / Q000201:enzymology*
D005994:Glycerophosphates; D008563:Membrane Lipids; D011106:Polyisoprenyl Phosphates; C545988:digeranylgeranylglycerol phosphate; C514638:(S)-2,3-di-O-geranylgeranylglyceryl phosphate synthase, Sulfolobus solfataricus; D004122:Dimethylallyltranstransferase