Biosynthesis of polyunsaturated fatty acids in lower eukaryotes

Abstract

SummaryPolyunsaturated fatty acids have important structural roles in cell membranes. They are also intermediates in the synthesis of biologically active molecules such as eicosanoids, which mediate fever, inflammation, blood pressure and neurotransmission. Arachidonic and docosahexaenoic acids are essential components of brain tissues and, through their involvement in the development of neural and retinal functions, important dietary nutrients for neonatal babies. Lower eukaryotes are particularly rich in C20-22 polyunsaturated fatty acids. Fungi and marine microalgae are currently used to produce nutraceutic oils. Other protists and algae are being studied because of the variability in their enzymes involved in polyunsaturated fatty acid biosynthesis. Such enzymes could be used as source for the production of transgenic organisms able to synthesize designed oils for human diet or, in the case of parasitic protozoa, they might be identified as putative chemotherapeutic targets. Polyunsaturated fatty acids can be synthesized by two different pathways: an anaerobic one, by using polyketide synthase related enzymes, and an aerobic one, which involves the action of elongases and oxygen dependent desaturases. Desaturases can be classified into three main types, depending on which of the consecutive steps of polyunsaturated fatty acid synthesis they are involved with. The enzymes may be specialized to act on: saturated substrates (type I); mono-and di-unsaturated fatty acids by introducing additional double bonds at the methyl-end site of the existing double bonds (type II); or the carboxy half ('front-end') of polyunsaturated ones (type III). Type III desaturases require the alternating action of elongases. A description of the enzymes that have been isolated and functionally characterized is provided, in order to highlight the different pathways found in lower eukaryotes.

NAD(P)H Cytochrome b5 Oxidoreductase Deficiency in Leishmania major Results in Impaired Linoleate Synthesis Followed by Increased Oxidative Stress and Cell Death

“…Trypanosomes have to take up precursors from the host to produce FAs beyond linoleate (18:2) as they apparently lack the desaturases that are required for processing linoleate further (7,8). All FADs require a redox partner for transferring electron from NAD(P)H (9). But until now nothing is known regarding the redox partner of FADs in Leishmania.…”

“…The membrane-bound cb 5 transfers electron from cb 5 r to the desaturase (27). In the other mode, cb 5 is itself included as an extra domain in the amino-terminal (9,28) or in the carboxylterminal end of desaturase (23,29) and mediates the electron transfer from cb 5 r to the desaturase.…”

Characterization of membrane-bound fatty acid desaturases

“…Genes from multicelluar organisms -arabidopsis, rat, oak and frog do not contain this domain. The reason of the cytochrome b 5 domain deletion from Δ9-desaturases is still unknown, but in a fact it was found only in the higher eukaryotes, whew diffusible cytochrome b 5 of the endoplasmic reticulum serves as electron donor in these cases (Uttaro 2006). Figure 7 also shows that the pattern of the His boxes corresponds to typical motif of Δ9-desaturase as follows: 1 st His box contains four amino acid residues between His residues and 3 rd His box contains H instead of Q.…”

“…Repetion of these steps results in synthesis of PUFA such as DHA. This pathway can be found in marine bacteria such as Shewanella or Photobacterium, and thraustochytrids such as Szichochytrium (Uttaro 2006). This strain is also an example of organisms that has possibility to synthesise PUFAs by anaerobic together with aerobic pathways.…”

Identification of a novel type of polyunsaturated fatty acid synthase involved in arachidonic acid biosynthesis

“…Two major pathways are known for PUFA biosynthesis. One is the aerobic pathway, in which saturated fatty acids synthesized by fatty acid synthase are desaturated and elongated by desaturases and elongases, respectively, to PUFAs [5][6][7]. The other is the anaerobic pathway, in which PUFAs are anaerobically synthesized from acetylCoA by PUFA synthases rather than multiple desaturation and elongation reactions [8,9].…”