Fatty acid synthesis by elongases in trypanosomes.

All eukaryotic and prokaryotic organisms are thought to synthesize fatty acids using a type I or type II synthase. In addition, eukaryotes extend pre-existing long chain fatty acids using microsomal elongases (ELOs). We have found that Trypanosoma brucei, a eukaryotic human parasite that causes sleeping sickness, uses three elongases instead of type I or type II synthases for the synthesis of nearly all its fatty acids. Trypanosomes encounter diverse environments during their life cycle with different fatty acid requirements. The tsetse vector form requires synthesis of stearate (C18), whereas the bloodstream form needs myristate (C14). We find that trypanosome fatty acid synthesis is modular, with EL01 converting C4 to C10, EL02 extending C1 0 to C14, and EL03 elongating C14 to C18. In blood, EL03 downregulation favors myristate synthesis, whereas low concentrations of exogenous fatty acids in cultured parasites cause upregulation of the entire pathway, allowing the parasite to adapt to different environments.