Improving the flux distributions simulated with genome-scale metabolic models of Saccharomyces cerevisiae
Artikel i vetenskaplig tidskrift, 2016

Genome-scale metabolic models (GEMs) can be used to evaluate genotype-phenotype relationships and their application to microbial strain engineering is increasing in popularity. Some of the algorithms used to simulate the phenotypes of mutant strains require the determination of a wild-type flux distribution. However, the accuracy of this reference, when calculated with flux balance analysis, has not been studied in detail before.Here, the wild-type simulations of selected GEMs for Saccharomyces cerevisiae have been analysed and most of the models tested predicted erroneous fluxes in central pathways, especially in the pentose phosphate pathway. Since the problematic fluxes were mostly related to areas of the metabolism consuming or producing NADPH/NADH, we have manually curated all reactions including these cofactors by forcing the use of NADPH/NADP+ in anabolic reactions and NADH/NAD+ for catabolic reactions. The curated models predicted more accurate flux distributions and performed better in the simulation of mutant phenotypes.

Metabolic engineering

Genome-scale metabolic model

Saccharomyces cerevisiae

Flux distribution

NADH: NADPH

Författare

Rui Pereira

Chalmers, Biologi och bioteknik, Systembiologi

Jens B Nielsen

Chalmers, Biologi och bioteknik, Systembiologi

I. Rocha

Universidade do Minho

Metabolic Engineering Communications

2214-0301 (eISSN)

Vol. 3 153-163

Styrkeområden

Livsvetenskaper och teknik

Ämneskategorier

Bioinformatik och systembiologi

DOI

10.1016/j.meteno.2016.05.002

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Senast uppdaterat

2018-02-28