Elongation of polyunsaturated fatty acids in trypanosomatids.

LIVORE, VERÓNICA; TRIPODI, KARINA E.J.; UTTARO, ANTONIO D.

FEBS Journal

Blackwell Publishing

Año: 2007 vol. 274 p. 264 - 274

1742-4658

Leishmania major synthesizes polyunsaturated fatty acids by using D6, D5and D4 front-enddesaturases,which have recently been characterized [Tri-podiKE,ButtiglieroLV,AltabeSG&UttaroAD(2006) FEBSJ 273,271280], and two predictedelongasesspecific for C18  D6 and C20 D5poly-unsaturated fattyacids, respectively. Trypanosomabrucei and Trypanosomacruzi lack D6and D5desaturases but contain D4desaturases, implying thattrypanosomes use exogenous polyunsaturated fatty acids to produce C22D4 fatty acids. In order to identify putative precursors of these C22 fattyacids and to completely describe the pathways for polyunsaturated fattyacid biosynthesis in trypanosomatids,we have performed a search in thethree genomes and identified fourdifferent elongasegenes in T.brucei,fivein T.cruzi and14 in L.major. After a phylogenetic analysis of the encodedproteins together with elongases from a variety of other organisms,we selec-ted four candidate polyunsaturated fatty acid elongases. Leishmania majorCAJ02037, T.brucei AAX69821 and T.cruzi XP_808770 share 57- 52%identity,and group together with C20 D5polyunsaturatedf atty acid elon-gases fromalgae.The predicted activity was corroborated by functionalcharacterization after expression in yeast. T.brucei elongase was also ableto elongate D8 and D11C20 polyunsaturated fatty acids. L.majorCAJ08636,which shares 33% identity with Mortierella alpina D6 elongase,showed a highspecificity for C18 D6polyunsaturated fatty acids.In allcases,a preference for n6 polyunsaturated fatty acids was observed.Thisindicates that L.major has,as predicted, D6 and D5 elongases and a com-plete pathway for polyunsaturated fatty acid biosynthesis.Trypanosomescontain only D5 elongases, which, together with D4desaturases,allow themto use eicosapentaenoic acid and arachidonicacid, a precursor that is rela-tively abundant in the host,for C22 polyunsaturated fatty acid biosynthesis.