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Extension of the yeast metabolic model to include iron metabolism and its use to estimate global levels of iron‐recruiting enzyme abundance from cofactor requirements
Author(s) -
Dikicioglu Duygu,
Oliver Stephen G.
Publication year - 2019
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.26905
Subject(s) - saccharomyces cerevisiae , metabolic network , enzyme , cofactor , biochemistry , metabolism , biology , in silico , metabolic pathway , yeast , metabolic engineering , gene
Metabolic networks adapt to changes in their environment by modulating the activity of their enzymes and transporters; often by changing their abundance. Understanding such quantitative changes can shed light onto how metabolic adaptation works, or how it can fail and lead to a metabolically dysfunctional state. We propose a strategy to quantify metabolic protein requirements for cofactor‐utilising enzymes and transporters through constraint‐based modelling. The first eukaryotic genome‐scale metabolic model to comprehensively represent iron metabolism was constructed, extending the most recent community model of the Saccharomyces cerevisiae metabolic network. Partial functional impairment of the genes involved in the maturation of iron‐sulphur (Fe‐S) proteins was investigated employing the model and the in silico analysis revealed extensive rewiring of the fluxes in response to this functional impairment, despite its marginal phenotypic effect. The optimal turnover rate of enzymes bearing ion cofactors can be determined via this novel approach; yeast metabolism, at steady state, was determined to employ a constant turnover of its iron‐recruiting enzyme at a rate of 3.02 × 10 −11 mmol·(g biomass) −1 ·h −1 .