Tymoshenko2015 - Genome scale metabolic model - ToxoNet1

Tymoshenko2015 - Genome scale metabolic model
- ToxoNet1

This model is described in the article:

Metabolic Needs and
Capabilities of Toxoplasma gondii through Combined
Computational and Experimental Analysis.

Tymoshenko S, Oppenheim RD, Agren R,
Nielsen J, Soldati-Favre D, Hatzimanikatis V.
PLoS Comput. Biol. 2015 May; 11(5):
e1004261
Abstract:

Toxoplasma gondii is a human pathogen prevalent worldwide
that poses a challenging and unmet need for novel treatment of
toxoplasmosis. Using a semi-automated reconstruction algorithm,
we reconstructed a genome-scale metabolic model, ToxoNet1. The
reconstruction process and flux-balance analysis of the model
offer a systematic overview of the metabolic capabilities of
this parasite. Using ToxoNet1 we have identified significant
gaps in the current knowledge of Toxoplasma metabolic pathways
and have clarified its minimal nutritional requirements for
replication. By probing the model via metabolic tasks, we have
further defined sets of alternative precursors necessary for
parasite growth. Within a human host cell environment, ToxoNet1
predicts a minimal set of 53 enzyme-coding genes and 76
reactions to be essential for parasite replication.
Double-gene-essentiality analysis identified 20 pairs of genes
for which simultaneous deletion is deleterious. To validate
several predictions of ToxoNet1 we have performed experimental
analyses of cytosolic acetyl-CoA biosynthesis. ATP-citrate
lyase and acetyl-CoA synthase were localised and their
corresponding genes disrupted, establishing that each of these
enzymes is dispensable for the growth of T. gondii, however
together they make a synthetic lethal pair.

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