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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

Dikicioglu, D; Oliver, SG; (2019) 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. Biotechnology and Bioengineering , 116 (3) pp. 610-621. 10.1002/bit.26905. Green open access

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Abstract

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.

Type: Article
Title: 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
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/bit.26905
Publisher version: http://dx.doi.org/10.1002/bit.26905
Language: English
Additional information: © 2018 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: enzyme cofactor turnover, iron metabolism, iron-sulphur maturation, metabolic networks, yeast, SULFUR PROTEIN BIOGENESIS, SACCHAROMYCES-CEREVISIAE, 1ST STEP, COPPER, CELLS, EUKARYOTES, EXPRESSION, GENE
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10109708
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