Fine‐tuning the P. pastoris iMT1026 genome‐scale metabolic model for improved prediction of growth on methanol or glycerol as sole carbon sources. Issue 1 (21st November 2017)

• Record Type: Journal Article
• Authors: Tomàs‐Gamisans, Màrius; Ferrer, Pau; Albiol, Joan
• Other Names: Aulenta Federico guestEditor.; Harnisch Falk guestEditor.; Puig Sebastià guestEditor.
• Is Part Of: Microbial biotechnology. Volume 11:Issue 1(2018:Jan.)
• Page Start: 224
• Page End: 237
• Publication Date: 2017-11-21
• Subjects: Microbial biotechnology -- Periodicals; Biotechnology; Microbiology; 660.62
• DOI: 10.1111/1751-7915.12871
• Languages: English
• ISSNs: 1751-7915

Abstract

Summary: The methylotrophic yeast Pichia pastoris ( Komagataella spp.) is widely used as cell factory for recombinant protein production. In the past recent years, important breakthroughs in the systems‐level quantitative analysis of its physiology have been achieved. This wealth of information has allowed the development of genome‐scale metabolic models, which make new approaches possible for host cell and bioprocess engineering. Nevertheless, the predictive accuracy of the previous consensus model required to be upgraded and validated with new experimental data sets for P. pastoris growing on glycerol or methanol as sole carbon sources, two of the most relevant substrates for this cell factory. In this study, we have characterized P. pastoris growing in chemostat cultures using glycerol or methanol as sole carbon sources over a wide range of growth rates, thereby providing physiological data on the effect of growth rate and culture conditions on biomass macromolecular and elemental composition. In addition, these data sets were used to improve the performance of the P. pastoris consensus genomic‐scale metabolic model iMT1026. Thereupon, new experimentally determined bounds, including the representation of biomass composition for these growth conditions, have been incorporated. As a result, here, we present version 3 (v3.0) of the consensus P. pastoris genome‐scale metabolic model as an update of the iMT1026 model. The v3.0 model was validated for growth on glycerol and methanol as sole carbon sources, demonstrating improved prediction capabilities over an extended substrate range including two biotechnologically relevant carbon sources. Abstract : In this study P. pastoris is characterised using chemostat cultures, with glycerol or methanol as sole carbon sources, and over a wide range of growth rates. As a result, new experimental physiological data, including the representation of biomass composition for these growth conditions is provided. In addition the derived biomass composition equations have been incorporated into iMT1026 (the consensus genome‐scale metabolic model for P. pastoris ). As a striking outcome, a new version of the GEM model iMT1026 (v3.0) is provided with enhanced and improved prediction capabilities.