African trypanosomiasis — or sleeping sickness — kills about 50,000 people each year according to the World Health Organization. Lee et al. (Cell 126, 691–699; 2006) report that the parasite responsible (Trypanosoma brucei, pictured) has an unusual way of making a lipid it requires to survive in the blood stream.
The extracellular surface of T. brucei is covered in proteins that are attached to the membrane through glycosylphosphatidylinositol (GPI) anchors. The bloodstream form of T. brucei needs a 14-carbon fatty acid to make the GPI anchors, and this molecule — named myristate — is essential for pathogenesis. Whereas most organisms synthesize fatty acids using type I or type II fatty-acid synthases, Lee et al. find that in T. brucei myristate is made by a series of enzymes called elongases. As their name implies, these enzymes extend the fatty-acid chain, adding two carbon atoms at a time to a fatty acid that is attached to coenzyme A (CoA).
The authors examined four candidate elongase (ELO) gene products and determined that ELO1 converts a 4-carbon CoA into a 10-carbon fatty acid; ELO2 uses a 10-carbon CoA to synthesize myristate; ELO3 converts a 14-carbon CoA into an 18-carbon fatty acid; and ELO4 elongates arachidonoyl-CoA into a 22-carbon fatty acid. It was previously known that ELOs could extend long fatty-acid chains, but this is the first example of a parasite that uses ELOs instead of type I or type II fatty-acid synthases to make a large fraction of its fatty acids.
The authors then examined two related parasites (Leishmania major and Trypanosoma cruzi) and determined that both organisms contain ELOs that are probably involved in fatty-acid biosynthesis. Additional work is needed to explore how ELOs function in vivo, but the authors suggest that it may be possible to exploit this unique pathway to develop new anti-parasitic drugs.