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

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...

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Autores principales: Darlington, Alexander P. S., Kim, Juhyun, Jiménez, José I., Bates, Declan G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814443/
https://www.ncbi.nlm.nih.gov/pubmed/29449554
http://dx.doi.org/10.1038/s41467-018-02898-6
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author Darlington, Alexander P. S.
Kim, Juhyun
Jiménez, José I.
Bates, Declan G.
author_facet Darlington, Alexander P. S.
Kim, Juhyun
Jiménez, José I.
Bates, Declan G.
author_sort Darlington, Alexander P. S.
collection PubMed
description 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 flux 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.
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spelling pubmed-58144432018-02-20 Dynamic allocation of orthogonal ribosomes facilitates uncoupling of co-expressed genes Darlington, Alexander P. S. Kim, Juhyun Jiménez, José I. Bates, Declan G. Nat Commun Article 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 flux 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. Nature Publishing Group UK 2018-02-15 /pmc/articles/PMC5814443/ /pubmed/29449554 http://dx.doi.org/10.1038/s41467-018-02898-6 Text en © 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/.
spellingShingle Article
Darlington, Alexander P. S.
Kim, Juhyun
Jiménez, José I.
Bates, Declan G.
Dynamic allocation of orthogonal ribosomes facilitates uncoupling of co-expressed genes
title Dynamic allocation of orthogonal ribosomes facilitates uncoupling of co-expressed genes
title_full Dynamic allocation of orthogonal ribosomes facilitates uncoupling of co-expressed genes
title_fullStr Dynamic allocation of orthogonal ribosomes facilitates uncoupling of co-expressed genes
title_full_unstemmed Dynamic allocation of orthogonal ribosomes facilitates uncoupling of co-expressed genes
title_short Dynamic allocation of orthogonal ribosomes facilitates uncoupling of co-expressed genes
title_sort dynamic allocation of orthogonal ribosomes facilitates uncoupling of co-expressed genes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814443/
https://www.ncbi.nlm.nih.gov/pubmed/29449554
http://dx.doi.org/10.1038/s41467-018-02898-6
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