Lipid Metabolism and Signalling


Research Leader: Dr Johnathan Napier

We are interested in the production of pharmaceutical essential fatty acids in transgenic plants. These are usually long chain (C18+) compounds containing three or more double bonds and are often referred to as PUFAs (polyunsaturated fatty acids). These include γ-linolenic acid (GLA; 18:3Δ^6,9,12) which is found in a few plant species such as evening primrose and borage; GLA is widely used as both a nutraceutical and pharmaceutical product. Other examples of (very long chain; C20+) PUFAs are arachidonic acid (AA; 20:4Δ^5,8,11,14) which is now known to be important in neonatal health and development, and eicosapentaenoic acid (EPA; 20:5Δ^5,8,11,14,17) which may play an important role in cardiovascular function. In animals, PUFAs also serve as precursors for the eicosanoids, a class of important biomedical metabolites which include the prostaglandins, leukotrienes and thromboxanes. The eicosanoid pathway does not occur in higher plants, though plant signalling compounds such jasmonic acid are produced by an analogous biochemical mechanism. 

Animals, including humans, have only a limited capacity to synthesise fatty acids. This has led to the identification of linoleic acid (LA;18:2Δ^9,12) and alpha-linolenic acid (ALA; 18:3Δ^9,12,15) as being essential components of dietary intake and are therefore classified as essential fatty acids (EFAs). In contrast to animals, higher plants produce a wide range of fatty acids, mainly through the actions of distinct desaturase enzymes. Unfortunately, many of the plant species which synthesise potentially useful fatty acids are unsuitable for modern agronomic practices, limiting the current opportunities for exploitation of their natural products. However, advances in plant biotechnology and gene transfer technologies has allowed researchers to utilise (and mobilise) this natural diversity as a source of traits which can be introduced into a more amenable agricultural plant species. 

The aims of our research programme are the identification of the genes involved in PUFA biosynthesis. We have studied a range of different organisms to further our understanding of PUFA biosynthesis. Not only have we cloned and characterised the Δ⁶-desaturase gene from borage (responsible for the synthesis of GLA) but we have also characterised fatty acid desaturases from both the fungal (Mortierella alpina) and animal (Caenorhrabditis elegans) sources. More recently we have succeeded in identifying components of the fatty acid elongase, which, when co-expressed with PUFA-specific desaturases resulted in the heterologous reconstitition of PUFA biosynthesis. 

Selected References: 
Beaudoin et al., (2000) Heterologous reconstitution in yeast of the polyunsaturated fatty acid biosynthetic pathway. Proc. Natl. Acad. Sci. USA 97: 6421-6426. 
Napier et al., (1999) Plant desaturases: harvesting the fat of the land. Curr. Opin. Plant Biol. 2: 123-127.