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Improving the phenotype predictions of a yeast genome-scale metabolic model by incorporating enzymatic constraints

Benjamin Sánchez (Institutionen för biologi och bioteknik, Systembiologi) ; Cheng Zhang ; Avlant Nilsson (Institutionen för biologi och bioteknik, Systembiologi) ; Petri-Jaan Lahtvee (Institutionen för biologi och bioteknik, Systembiologi) ; Eduard Kerkhoven (Institutionen för biologi och bioteknik, Systembiologi) ; Jens B. Nielsen (Institutionen för biologi och bioteknik, Systembiologi)
MOLECULAR SYSTEMS BIOLOGY (1744-4292). Vol. 13 (2017), 8, p. Article no 935 .
[Artikel, refereegranskad vetenskaplig]

Genome-scale metabolic models (GEMs) are widely used to calculate metabolic phenotypes. They rely on defining a set of constraints, the most common of which is that the production of metabolites and/or growth are limited by the carbon source uptake rate. However, enzyme abundances and kinetics, which act as limitations on metabolic fluxes, are not taken into account. Here, we present GECKO, a method that enhances a GEM to account for enzymes as part of reactions, thereby ensuring that each metabolic flux does not exceed its maximum capacity, equal to the product of the enzyme's abundance and turnover number. We applied GECKO to a Saccharomyces cerevisiae GEM and demonstrated that the new model could correctly describe phenotypes that the previous model could not, particularly under high enzymatic pressure conditions, such as yeast growing on different carbon sources in excess, coping with stress, or overexpressing a specific pathway. GECKO also allows to directly integrate quantitative proteomics data; by doing so, we significantly reduced flux variability of the model, in over 60% of metabolic reactions. Additionally, the model gives insight into the distribution of enzyme usage between and within metabolic pathways. The developed method and model are expected to increase the use of model-based design in metabolic engineering.

Nyckelord: saccharomyces-cerevisiae, escherichia-coli, growth-rate, quantitative prediction, fermentative capacity, protein, expression, evolutionary, quantification, integration



Denna post skapades 2017-08-28. Senast ändrad 2017-09-06.
CPL Pubid: 251460

 

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Institutioner (Chalmers)

Institutionen för biologi och bioteknik, Systembiologi

Ämnesområden

Bioinformatik och systembiologi

Chalmers infrastruktur