ABSTRACT:
Chung2010 - Genome-scale metabolic network of
Pichia pastoris (iPP668)
This model is described in the article:
Genome-scale metabolic
reconstruction and in silico analysis of methylotrophic yeast
Pichia pastoris for strain improvement.
Chung BK, Selvarasu S, Andrea C, Ryu
J, Lee H, Ahn J, Lee H, Lee DY.
Microb. Cell Fact. 2010; 9: 50
Abstract:
BACKGROUND: Pichia pastoris has been recognized as an
effective host for recombinant protein production. A number of
studies have been reported for improving this expression
system. However, its physiology and cellular metabolism still
remained largely uncharacterized. Thus, it is highly desirable
to establish a systems biotechnological framework, in which a
comprehensive in silico model of P. pastoris can be employed
together with high throughput experimental data analysis, for
better understanding of the methylotrophic yeast's metabolism.
RESULTS: A fully compartmentalized metabolic model of P.
pastoris (iPP668), composed of 1,361 reactions and 1,177
metabolites, was reconstructed based on its genome annotation
and biochemical information. The constraints-based flux
analysis was then used to predict achievable growth rate which
is consistent with the cellular phenotype of P. pastoris
observed during chemostat experiments. Subsequent in silico
analysis further explored the effect of various carbon sources
on cell growth, revealing sorbitol as a promising candidate for
culturing recombinant P. pastoris strains producing
heterologous proteins. Interestingly, methanol consumption
yields a high regeneration rate of reducing equivalents which
is substantial for the synthesis of valuable pharmaceutical
precursors. Hence, as a case study, we examined the
applicability of P. pastoris system to whole-cell
biotransformation and also identified relevant metabolic
engineering targets that have been experimentally verified.
CONCLUSION: The genome-scale metabolic model characterizes the
cellular physiology of P. pastoris, thus allowing us to gain
valuable insights into the metabolism of methylotrophic yeast
and devise possible strategies for strain improvement through
in silico simulations. This computational approach, combined
with synthetic biology techniques, potentially forms a basis
for rational analysis and design of P. pastoris metabolic
network to enhance humanized glycoprotein production.
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Nicolas Le Novère 
