title: Genome-scale metabolic model of methylotrophic yeast Pichia pastoris and its use for in silico analysis of heterologous protein production.
abstract: The methylotrophic yeast Pichia pastoris has gained much attention during the last decade as a platform for producing heterologous recombinant proteins of pharmaceutical importance, due to its ability to reproduce post-translational modification similar to higher eukaryotes. With the recent release of the full genome sequence for P. pastoris, in-depth study of its functions has become feasible. Here we present the first reconstruction of the genome-scale metabolic model of the eukaryote P. pastoris type strain DSMZ 70382, PpaMBEL1254, consisting of 1254 metabolic reactions and 1147 metabolites compartmentalized into eight different regions to represent organelles. Additionally, equations describing the production of two heterologous proteins, human serum albumin and human superoxide dismutase, were incorporated. The protein-producing model versions of PpaMBEL1254 were then analyzed to examine the impact on oxygen limitation on protein production.
authors.affiliation: Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 program), Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, KAIST, 335 Gwahangno, Daejeon, Republic of Korea.
authors.forename: Seung Bum
authors.initials: SB
authors.lastname: Sohn
authors.forename: Alexandra B
authors.initials: AB
authors.lastname: Graf
authors.forename: Tae Yong
authors.initials: TY
authors.lastname: Kim
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gasser
authors.forename: Michael
authors.initials: M
authors.lastname: Maurer
authors.forename: Pau
authors.initials: P
authors.lastname: Ferrer
authors.forename: Diethard
authors.initials: D
authors.lastname: Mattanovich
authors.forename: Sang Yup
authors.initials: SY
authors.lastname: Lee
mesh_terms: D003470:Culture Media; D030562:Databases, Protein; D005285:Fermentation; D006801:Humans; D008954:Models, Biological; D010843:Pichia / Q000378:metabolism*; D015202:Protein Engineering; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000096:biosynthesis* / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D012709:Serum Albumin / Q000096:biosynthesis; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics
chemical_list: D003470:Culture Media; D011994:Recombinant Proteins; D012709:Serum Albumin; D013482:Superoxide Dismutase