Chavali2008 - Genome-scale metabolic network of Leishmania major (iAC560)

Chavali2008 - Genome-scale metabolic network
of Leishmania major (iAC560)

This model is described in the article:

Systems analysis of
metabolism in the pathogenic trypanosomatid Leishmania
major.

Chavali AK, Whittemore JD, Eddy JA,
Williams KT, Papin JA.
Mol. Syst. Biol. 2008; 4: 177
Abstract:

Systems analyses have facilitated the characterization of
metabolic networks of several organisms. We have reconstructed
the metabolic network of Leishmania major, a poorly
characterized organism that causes cutaneous leishmaniasis in
mammalian hosts. This network reconstruction accounts for 560
genes, 1112 reactions, 1101 metabolites and 8 unique
subcellular localizations. Using a systems-based approach, we
hypothesized a comprehensive set of lethal single and double
gene deletions, some of which were validated using published
data with approximately 70% accuracy. Additionally, we
generated hypothetical annotations to dozens of previously
uncharacterized genes in the L. major genome and proposed a
minimal medium for growth. We further demonstrated the utility
of a network reconstruction with two proof-of-concept examples
that yielded insight into robustness of the network in the
presence of enzymatic inhibitors and delineation of
promastigote/amastigote stage-specific metabolism. This
reconstruction and the associated network analyses of L. major
is the first of its kind for a protozoan. It can serve as a
tool for clarifying discrepancies between data sources,
generating hypotheses that can be experimentally validated and
identifying ideal therapeutic targets.

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