A new approach for potential drug target discovery through in silico metabolic pathway analysis using Trypanosoma cruzi genome information

摘要

The current drug options for the treatment of chronic Chagas disease have not been sufficient and high hopeshave been placed on the use of genomic data from the human parasite Trypanosoma cruzi to identify new drug targetsand develop appropriate treatments for both acute and chronic Chagas disease. However, the lack of a completeassembly of the genomic sequence and the presence of many predicted proteins with unknown or unsure functionshas hampered our complete view of the parasite’s metabolic pathways. Moreover, pinpointing new drug targets hasproven to be more complex than anticipated and has revealed large holes in our understanding of metabolic pathwaysand their integrated regulation, not only for this parasite, but for many other similar pathogens. Using an insilico comparative study on pathway annotation and searching for analogous and specific enzymes, we have beenable to predict a considerable number of additional enzymatic functions in T. cruzi. Here we focus on the energeticpathways, such as glycolysis, the pentose phosphate shunt, the Krebs cycle and lipid metabolism. We point out manyenzymes that are analogous to those of the human host, which could be potential new therapeutic targets.