Estimating the protein burden limit of yeast cells by measuring the expression limits of glycolytic proteins

The ultimate overexpression of a protein could cause growth defects, which are known as the protein burden. However, the expression limit at which the protein-burden effect is triggered is still unclear. To estimate this limit, we systematically measured the overexpression limits of glycolytic prote...

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Main Authors: Yuichi Eguchi, Koji Makanae, Tomohisa Hasunuma, Yuko Ishibashi, Keiji Kito, Hisao Moriya
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2018-08-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/34595
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author Yuichi Eguchi
Koji Makanae
Tomohisa Hasunuma
Yuko Ishibashi
Keiji Kito
Hisao Moriya
author_facet Yuichi Eguchi
Koji Makanae
Tomohisa Hasunuma
Yuko Ishibashi
Keiji Kito
Hisao Moriya
author_sort Yuichi Eguchi
collection DOAJ
description The ultimate overexpression of a protein could cause growth defects, which are known as the protein burden. However, the expression limit at which the protein-burden effect is triggered is still unclear. To estimate this limit, we systematically measured the overexpression limits of glycolytic proteins in Saccharomyces cerevisiae. The limits of some glycolytic proteins were up to 15% of the total cellular protein. These limits were independent of the proteins’ catalytic activities, a finding that was supported by an in silico analysis. Some proteins had low expression limits that were explained by their localization and metabolic perturbations. The codon usage should be highly optimized to trigger the protein-burden effect, even under strong transcriptional induction. The S–S-bond-connected aggregation mediated by the cysteine residues of a protein might affect its expression limit. Theoretically, only non-harmful proteins could be expressed up to the protein-burden limit. Therefore, we established a framework to distinguish proteins that are harmful and non-harmful upon overexpression.
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spelling doaj.art-e0a64d5f20db440ca7ad074a50a788322022-12-22T03:52:15ZengeLife Sciences Publications LtdeLife2050-084X2018-08-01710.7554/eLife.34595Estimating the protein burden limit of yeast cells by measuring the expression limits of glycolytic proteinsYuichi Eguchi0https://orcid.org/0000-0002-4809-1402Koji Makanae1Tomohisa Hasunuma2Yuko Ishibashi3Keiji Kito4Hisao Moriya5https://orcid.org/0000-0001-7638-3640Graduate School of Environmental and Life Science, Okayama University, Okayama, JapanResearch Core for Interdisciplinary Sciences, Okayama University, Okayama, JapanGraduate School of Science, Technology and Innovation, Kobe University, Kobe, JapanDepartment of Life Sciences, School of Agriculture, Meiji University, Kawasaki, JapanDepartment of Life Sciences, School of Agriculture, Meiji University, Kawasaki, JapanGraduate School of Environmental and Life Science, Okayama University, Okayama, Japan; Research Core for Interdisciplinary Sciences, Okayama University, Okayama, JapanThe ultimate overexpression of a protein could cause growth defects, which are known as the protein burden. However, the expression limit at which the protein-burden effect is triggered is still unclear. To estimate this limit, we systematically measured the overexpression limits of glycolytic proteins in Saccharomyces cerevisiae. The limits of some glycolytic proteins were up to 15% of the total cellular protein. These limits were independent of the proteins’ catalytic activities, a finding that was supported by an in silico analysis. Some proteins had low expression limits that were explained by their localization and metabolic perturbations. The codon usage should be highly optimized to trigger the protein-burden effect, even under strong transcriptional induction. The S–S-bond-connected aggregation mediated by the cysteine residues of a protein might affect its expression limit. Theoretically, only non-harmful proteins could be expressed up to the protein-burden limit. Therefore, we established a framework to distinguish proteins that are harmful and non-harmful upon overexpression.https://elifesciences.org/articles/34595protein burdenoverexpressionglycolysis
spellingShingle Yuichi Eguchi
Koji Makanae
Tomohisa Hasunuma
Yuko Ishibashi
Keiji Kito
Hisao Moriya
Estimating the protein burden limit of yeast cells by measuring the expression limits of glycolytic proteins
eLife
protein burden
overexpression
glycolysis
title Estimating the protein burden limit of yeast cells by measuring the expression limits of glycolytic proteins
title_full Estimating the protein burden limit of yeast cells by measuring the expression limits of glycolytic proteins
title_fullStr Estimating the protein burden limit of yeast cells by measuring the expression limits of glycolytic proteins
title_full_unstemmed Estimating the protein burden limit of yeast cells by measuring the expression limits of glycolytic proteins
title_short Estimating the protein burden limit of yeast cells by measuring the expression limits of glycolytic proteins
title_sort estimating the protein burden limit of yeast cells by measuring the expression limits of glycolytic proteins
topic protein burden
overexpression
glycolysis
url https://elifesciences.org/articles/34595
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