Our group has depicted the fatty acid and sphingolipid metabolisms in trypanosomatids. These organisms are responsible of serious human and animal diseases such as Chagas disease, caused by Trypanosoma cruzi, sleeping sickness (T. brucei) and leishmaniasis (Leishmania spp.). By mean of genetic approaches and the design of specific inhibitors, we have identified that two enzymes of the pathway are essential for the parasites, the D9 and D12 desaturases. We continue analyzing the essentiality of other desaturases and elongases, and developing new drugs, more efficacious and with potential clinical use. A new line of research focuses on the enzymes involved in lipoic acid biosynthesis.
Another line of work focuses on the metabolism of sterols in the ciliates Tetrahymena thermophila and Paramecium tetraurelia. T. thermophila is able of taking up sterols from the media and modifying them by a series of desaturations and dealkylation. By using reverse genetic approaches such as feeding-RNA interference and knock out mutagenesis, we succeeded identifying the D5 and D6 desaturases and the dealkylating enzyme, which is the first one described in nature. The consequence of these reactions is the synthesis of pro-vitamin D, which is accumulated in the ciliate membrane. This has obvious biotechnological applications in the creation of functional foods of animal origin, with the dual benefit of reducing cholesterol and the concomitant enrichment in pro-vitamin D. We are also studying the synthesis of glycogen and triglycerides, which act as carbon and energy stores. We have determined that glycerol (a cheap by-product of the biodiesel industry) is a good carbon source for the ciliates, repressing the accumulation of glycogen, but stimulating the synthesis of triglycerides, which can be used in biodiesel production.