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Cell-free prediction of protein expression costs for growing cells

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Title: Cell-free prediction of protein expression costs for growing cells
Authors: Borkowski, O
Bricio, C
Murgiano, M
Rothschild-Mancinelli, B
Stan, G
Ellis, T
Item Type: Journal Article
Abstract: Translating heterologous proteins places significant burden on host cells, consuming expression resources leading to slower cell growth and productivity. Yet predicting the cost of protein production for any given gene is a major challenge, as multiple processes and factors combine to determine translation efficiency. To enable prediction of the cost of gene expression in bacteria, we describe here a standard cell-free lysate assay that provides a relative measure of resource consumption when a protein coding sequence is expressed. These lysate measurements can then be used with a computational model of translation to predict the in vivo burden placed on growing E. coli cells for a variety of proteins of different functions and lengths. Using this approach, we can predict the burden of expressing multigene operons of different designs and differentiate between the fraction of burden related to gene expression compared to action of a metabolic pathway.
Issue Date: 13-Apr-2018
Date of Acceptance: 26-Mar-2018
URI: http://hdl.handle.net/10044/1/58614
DOI: https://dx.doi.org/10.1038/s41467-018-03970-x
ISSN: 2041-1723
Publisher: Nature Publishing Group
Journal / Book Title: Nature Communications
Volume: 9
Copyright Statement: © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article ’ s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article ’ s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/
Sponsor/Funder: Engineering & Physical Science Research Council (EPSRC)
Engineering & Physical Science Research Council (EPSRC)
Engineering & Physical Science Research Council (EPSRC)
Funder's Grant Number: EP/M002306/1
EP/M002187/1
EP/P009352/1
Keywords: MD Multidisciplinary
Publication Status: Published
Article Number: ARTN 1457
Appears in Collections:Faculty of Engineering
Bioengineering



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