Fig 1.
Schematic overview of the major steps involved in the construction of P. pastoris GEM iMT1026.
The process of GEMs integration started with the metabolite identification, unifying nomenclature and curation steps of iPP668, PpaMBEL1254 and iLC915. The continuation steps were performed on the resulting pre-merged model and subsequent drafts. Experimental data for model validation was taken from [25, 60, 61, 66].
Table 1.
Comparison of the main features of iMT1026 and previous P. pastoris’ GEMs.
Fig 2.
Reactions from PpaMBEL1254, iPP668 and iLC915 included in iMT1026 model.
Table 2.
Evaluation of the substrate assimilation capabilities in P. pastoris.
Fig 3.
Summary of reaction essentiality results for glucose simulations grouped into major pathways.
FBA was performed by optimizing biomass production and sequentially constraining to 0 each reaction in the corresponding simulations. The resulting growth rate was compared with the wild type one. Metabolic reactions were classified in three categories according to the relative growth rate obtained: Essential (E), partially-essential (PE) and non-essential (NE). X axis represent the fraction of each type of reactions in each category of E (in red), PE (in blue) and NE (in green). Reactions are distributed in 8 major subsystems (Y axis). Numbers between brackets indicate number of reactions in each group. Equivalent figures for oxygen limiting conditions and glycerol:methanol simulations can be found in S1 Fig.
Fig 4.
Results of the model validation.
Graphs with (A) growth rate (B) CO2 and (C) D-arabitol production predictions when simulating glucose chemostats at different oxygen conditions, with and without recombinant protein production [60, 66] with glucose, O2 and ethanol fluxes constrained to the experimental values. (D) Growth rate (E) CO2 production and (F) O2 consumption predictions when simulating different glycerol:methanol chemostats [25, 61]. White and black bars correspond to experimental and predicted data respectively.* Not determined in [25].