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DOI | 10.1073/pnas.2020154118 |
Yeast optimizes metal utilization based on metabolic network and enzyme kinetics | |
Chen Y.; Li F.; Mao J.; Chen Y.; Nielsen J. | |
发表日期 | 2021 |
ISSN | 00278424 |
卷号 | 118期号:12 |
英文摘要 | Metal ions are vital to metabolism, as they can act as cofactors on enzymes and thus modulate individual enzymatic reactions. Although many enzymes have been reported to interact with metal ions, the quantitative relationships between metal ions and metabolism are lacking. Here, we reconstructed a genome-scale metabolic model of the yeast Saccharomyces cerevisiae to account for proteome constraints and enzyme cofactors such as metal ions, named CofactorYeast. The model is able to estimate abundances of metal ions binding on enzymes in cells under various conditions, which are comparable to measured metal ion contents in biomass. In addition, the model predicts distinct metabolic flux distributions in response to reduced levels of various metal ions in the medium. Specifically, the model reproduces changes upon iron deficiency in metabolic and gene expression levels, which could be interpreted by optimization principles (i.e., yeast optimizes iron utilization based on metabolic network and enzyme kinetics rather than preferentially targeting iron to specific enzymes or pathways). At last, we show the potential of using the model for understanding cell factories that harbor heterologous iron-containing enzymes to synthesize high-value compounds such as p-coumaric acid. Overall, the model demonstrates the dependence of enzymes on metal ions and links metal ions to metabolism on a genome scale. © 2021 National Academy of Sciences. All rights reserved. |
英文关键词 | Constraint-based model; Metabolic engineering; Proteome constraint; Resource allocation; Saccharomyces cerevisiae |
语种 | 英语 |
scopus关键词 | metal ion; para coumaric acid; proteome; Article; biomass; controlled study; enzyme binding; enzyme kinetics; fungal cell; gene expression; iron deficiency; metabolic engineering; metabolic flux analysis; metal metabolism; nonhuman; population abundance; prediction; priority journal; process optimization; protein synthesis; Saccharomyces cerevisiae |
来源期刊 | Proceedings of the National Academy of Sciences of the United States of America
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文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/180191 |
作者单位 | Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, SE412 96, Sweden; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs. Lyngby, DK2800, Denmark; BioInnovation Institute, Copenhagen N, DK2200, Denmark |
推荐引用方式 GB/T 7714 | Chen Y.,Li F.,Mao J.,et al. Yeast optimizes metal utilization based on metabolic network and enzyme kinetics[J],2021,118(12). |
APA | Chen Y.,Li F.,Mao J.,Chen Y.,&Nielsen J..(2021).Yeast optimizes metal utilization based on metabolic network and enzyme kinetics.Proceedings of the National Academy of Sciences of the United States of America,118(12). |
MLA | Chen Y.,et al."Yeast optimizes metal utilization based on metabolic network and enzyme kinetics".Proceedings of the National Academy of Sciences of the United States of America 118.12(2021). |
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