New cardiolipin analogs synthesized by phospholipase D-catalyzed transphosphatidylation

• Published in: Chemistry and physics of lipids 2012-10, Vol.165 (7), p.787-793
• Main Authors: Müller, Anna O., Mrestani-Klaus, Carmen, Schmidt, Jürgen, Ulbrich-Hofmann, Renate, Dippe, Martin
• Format: Article
• Language: English
• Subjects: Cardiolipin analogs; Cardiolipins - chemistry; Catalysis; choline; Diphosphatidyl lipids; ethanolamine; Ethanolamine derivatives; ethylene glycol; glycerol; Head group; Molecular Structure; phosphatidylcholines; Phosphatidylethanolamines - chemical synthesis; Phosphatidylethanolamines - chemistry; Phosphatidylserines - chemical synthesis; Phosphatidylserines - chemistry; Phospholipase D; Phospholipase D - chemistry; Spectrometry, Mass, Electrospray Ionization; Spectroscopy, Fourier Transform Infrared; Streptomyces; Streptomyces - enzymology; synthesis; Transphosphatidylation
• ISSN: 0009-3084; 1873-2941
• DOI: 10.1016/j.chemphyslip.2012.09.005

[Display omitted] ► Phospholipase D catalyzes the synthesis of cardiolipin-analogous phospholipids. ► The enzyme strongly favors ethanolamine derivatives with low molecular volume. ► Non-charged alcohols were only poorly introduced into the cardiolipin structure. Cardiolipin (CL) and related diphosphatidyl lipids are hardly accessible because of the complexity of their chemical synthesis. In the present paper, the transphosphatidylation reaction catalyzed by phospholipase D (PLD) from Streptomyces sp. has been proven as an alternative enzyme-assisted strategy for the synthesis of new CL analogs. The formation of this type of compounds from phosphatidylcholine was compared for a series of N- and C2-substituted ethanolamine derivatives as well as non-charged alcohols such as glycerol and ethylene glycol. The rapid exchange of the choline head group by ethanolamine derivatives having a low molecular volume (diethanolamine and serinol) gave rise to an efficient production of the corresponding CL analogs. In contrast, the yields were comparably low in the reaction with bulky nitrogenous acceptor alcohols (triethanolamine, tris(hydroxymethyl)aminomethane, tetrakis(hydroxyethyl)ammonium) or the non-charged alcohols. Therefore, a strong dependence of the conversion of the monophosphatidyl to the diphosphatidyl compound on steric parameters and the head group charge was concluded. The enzyme-assisted strategy was used for the preparation of purified diphosphatidyldiethanolamine and diphosphatidylserinol.