Highly specific methyl-end fatty-acid desaturases of trypanosomatids

A detailed analysis of the trypanosomatids' genome projects revealed the presence of genes predicted to encode fatty-acid desaturases of the methyl-end type (MED). After cloning and functional characterization of all identified genes, it can be concluded that Trypanosoma cruzi contains two MEDs with oleate desaturase (OD) activities whereas Leishmania major contains one OD and two active linoleate desaturases (LD). All characterized ODs are highly specific for oleate (18:1Δ9) as substrate, presenting a ν + 3 regioselectivity, although palmitoleate (16:1Δ9) can be desaturated as well, but to a lesser extent. L. major LD appears to use exclusively linoleate (18:2n-6), converting it into α-linolenate (18:3n-3). This strong specificity assures no further conversion of polyunsaturated fatty acids (PUFAs) of the n-6 series into the n-3 series, downstream in the PUFA biosynthesis pathway. This characterization completes the identification of all enzymes involved in PUFA biosynthesis in a parasitic protist. Differently from their Trypanosoma brucei orthologue, T. cruzi and L. major ODs were more active when expressed either, in the presence of trienoic fatty acids or at higher temperatures. This could be evidence for a differential post-translational regulation of these enzymes as a result of direct sensing of environmentally dependent parameters such as membrane fluidity.

Highly specific linoleate desaturase allows Leishmania major to synthesize both n-6 and n-3 polyunsaturated fatty acids without further interconversion of them downstream in the pathway.64Research highlights▶ Trypanosomatids contain highly specific oleate desaturases. ▶ Leishmania linoleate desaturase specifically converts linoleate into α-linolenate. ▶ LD does not desaturate other n-6 fatty acids into n-3 ones. ▶ LD is the major responsible establishing the final n-6/n-3 fatty acids ratio.