Fine-tuning the P. pastoris iMT1026 genome-scale metabolic model for improved prediction of growth on methanol or glycerol as sole carbon sources
Tomàs Gamisans, Màrius (Universitat Autònoma de Barcelona. Departament d'Enginyeria Química, Biològica i Ambiental)
Ferrer, Pau (Universitat Autònoma de Barcelona. Departament d'Enginyeria Química, Biològica i Ambiental)
Albiol i Sala, Joan (Universitat Autònoma de Barcelona. Departament d'Enginyeria Química, Biològica i Ambiental)

Data:	2018
Resum:	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 1026. 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 1026 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.
Ajuts:	Ministerio de Educación y Ciencia FPU12/06185 Ministerio de Economía y Competitividad CTQ2013-42391-R Ministerio de Economía y Competitividad CTQ2016-74959-R Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-452
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Microbial biotechnology, Vol. 11, Issue 1 (January 2018) , p. 224-237, ISSN 1751-7915

DOI: 10.1111/1751-7915.12871
PMID: 29160039

14 p, 611.6 KB

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