Beste2007 - Genome-scale metabolic network of Mycobacterium tuberculosis (GSMN_TB)

Beste2007 - Genome-scale metabolic network of
Mycobacterium tuberculosis (GSMN_TB)

This model is described in the article:

GSMN-TB: a web-based
genome-scale network model of Mycobacterium tuberculosis
metabolism.

Beste DJ, Hooper T, Stewart G, Bonde
B, Avignone-Rossa C, Bushell ME, Wheeler P, Klamt S, Kierzek AM,
McFadden J.
Genome Biol. 2007; 8(5): R89
Abstract:

BACKGROUND: An impediment to the rational development of
novel drugs against tuberculosis (TB) is a general paucity of
knowledge concerning the metabolism of Mycobacterium
tuberculosis, particularly during infection. Constraint-based
modeling provides a novel approach to investigating microbial
metabolism but has not yet been applied to genome-scale
modeling of M. tuberculosis. RESULTS: GSMN-TB, a genome-scale
metabolic model of M. tuberculosis, was constructed, consisting
of 849 unique reactions and 739 metabolites, and involving 726
genes. The model was calibrated by growing Mycobacterium bovis
bacille Calmette Guérin in continuous culture and
steady-state growth parameters were measured. Flux balance
analysis was used to calculate substrate consumption rates,
which were shown to correspond closely to experimentally
determined values. Predictions of gene essentiality were also
made by flux balance analysis simulation and were compared with
global mutagenesis data for M. tuberculosis grown in vitro. A
prediction accuracy of 78% was achieved. Known drug targets
were predicted to be essential by the model. The model
demonstrated a potential role for the enzyme isocitrate lyase
during the slow growth of mycobacteria, and this hypothesis was
experimentally verified. An interactive web-based version of
the model is available. CONCLUSION: The GSMN-TB model
successfully simulated many of the growth properties of M.
tuberculosis. The model provides a means to examine the
metabolic flexibility of bacteria and predict the phenotype of
mutants, and it highlights previously unexplored features of M.
tuberculosis metabolism.

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