Subrmanian2015 - Energy metabolism of Leishmania infantum, constrain-based metabolic model

The uploaded model is linked to the PLoS ONE article: Subramanian A, Jhawar J, Sarkar RR (2015) Dissecting Leishmania infantum Energy Metabolism - A Systems Perspective. PLoS ONE 10(9): e0137976. https://doi.org/10.1371/journal.pone.0137976. The reconstructed network consists of 142 genes encoding for enzymes performing 237 reactions distributed across five distinct model compartments. We annotated the subcellular locations of different enzymes and their reactions on the basis of strong literature evidence and sequence-based detection of cellular localization signal within a protein sequence. We also predicted an extensive set of lethal reaction knockouts; some of which were validated using published data on Leishmania species. Performing a robustness analysis, the model was rigorously validated and tested for the secretion of overflow metabolites specific to Leishmania under varying extracellular oxygen uptake rate. Stage-specific scenarios of L. infantum energy metabolism were incorporated in the model and key metabolic differences were outlined. Analysis of the model revealed the essentiality of glucose uptake, succinate fermentation, glutamate biosynthesis and an active TCA cycle as driving forces for parasite energy metabolism and its optimal growth. Finally, through our in silico knockout analysis, we could identify possible therapeutic targets that provide experimentally testable hypotheses.