ABSTRACT:
Caspeta2012 - Genome-scale metabolic network
of Pichia pastoris (iLC915)
This model is described in the article:
Genome-scale metabolic
reconstructions of Pichia stipitis and Pichia pastoris and in
silico evaluation of their potentials.
Caspeta L, Shoaie S, Agren R,
Nookaew I, Nielsen J.
BMC Syst Biol 2012; 6: 24
Abstract:
BACKGROUND: Pichia stipitis and Pichia pastoris have long
been investigated due to their native abilities to metabolize
every sugar from lignocellulose and to modulate methanol
consumption, respectively. The latter has been driving the
production of several recombinant proteins. As a result,
significant advances in their biochemical knowledge, as well as
in genetic engineering and fermentation methods have been
generated. The release of their genome sequences has allowed
systems level research. RESULTS: In this work, genome-scale
metabolic models (GEMs) of P. stipitis (iSS884) and P. pastoris
(iLC915) were reconstructed. iSS884 includes 1332 reactions,
922 metabolites, and 4 compartments. iLC915 contains 1423
reactions, 899 metabolites, and 7 compartments. Compared with
the previous GEMs of P. pastoris, PpaMBEL1254 and iPP668,
iLC915 contains more genes and metabolic functions, as well as
improved predictive capabilities. Simulations of physiological
responses for the growth of both yeasts on selected carbon
sources using iSS884 and iLC915 closely reproduced the
experimental data. Additionally, the iSS884 model was used to
predict ethanol production from xylose at different oxygen
uptake rates. Simulations with iLC915 closely reproduced the
effect of oxygen uptake rate on physiological states of P.
pastoris expressing a recombinant protein. The potential of P.
stipitis for the conversion of xylose and glucose into ethanol
using reactors in series, and of P. pastoris to produce
recombinant proteins using mixtures of methanol and glycerol or
sorbitol are also discussed. CONCLUSIONS: In conclusion the
first GEM of P. stipitis (iSS884) was reconstructed and
validated. The expanded version of the P. pastoris GEM, iLC915,
is more complete and has improved capabilities over the
existing models. Both GEMs are useful frameworks to explore the
versatility of these yeasts and to capitalize on their
biotechnological potentials.
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Nicolas Le Novère 
