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Dynamic allocation of orthogonal ribosomes facilitates uncoupling of co-expressed genes

Darlington, Alexander P.S., Kim, Juhyun, Jimenez, Jose and Bates, Declan G. (2018) Dynamic allocation of orthogonal ribosomes facilitates uncoupling of co-expressed genes Nature Communications, 9, 695.

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Abstract

Introduction of synthetic circuits into microbes creates competition between circuit and host genes for shared cellular resources, such as ribosomes. This can lead to the emergence of unwanted coupling between the expression of different circuit genes, complicating the design process and potentially leading to circuit failure. By expressing a synthetic 16S rRNA with altered specificity, we can partition the ribosome pool into host-specific and circuit-specific activities. We show mathematically and experimentally that the effects of resource competition can be alleviated by targeting genes to different ribosomal pools. This division of labour can be used to increase ux through a metabolic pathway. We develop a model of cell physiology which is able to capture these observations and use it to design a dynamic resource allocation controller. When implemented, this controller acts to decouple genes by increasing orthogonal ribosome production as the demand for translational resources by a synthetic circuit increases.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Darlington, Alexander P.S.
Kim, Juhyunjuhyun.kim@surrey.ac.uk
Jimenez, Josej.jimenez@surrey.ac.uk
Bates, Declan G.
Date : 15 February 2018
Identification Number : 10.1038/s41467-018-02898-6
Copyright Disclaimer : © The Author(s) 2018. Open Access 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/.
Uncontrolled Keywords : Metabolic engineering; Ribosome; Synthetic biology
Depositing User : Clive Harris
Date Deposited : 17 Jan 2018 08:52
Last Modified : 14 Mar 2018 08:34
URI: http://epubs.surrey.ac.uk/id/eprint/845630

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