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Dynamic allocation of orthogonal ribosomes facilitates uncoupling of co-expressed genes
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Darlington, Alexander P. S., Kim, Juhyun, Jiménez, José I. and Bates, Declan (2018) Dynamic allocation of orthogonal ribosomes facilitates uncoupling of co-expressed genes. Nature Communications, 9 (1). 695. doi:10.1038/s41467-018-02898-6 ISSN 2041-1723.
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Official URL: https://doi.org/10.1038/s41467-018-02898-6
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 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.
Item Type: | Journal Article | |||||||||||||||
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Subjects: | Q Science > QH Natural history > QH426 Genetics Q Science > QR Microbiology |
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Divisions: | Faculty of Science, Engineering and Medicine > Engineering > Engineering | |||||||||||||||
SWORD Depositor: | Library Publications Router | |||||||||||||||
Library of Congress Subject Headings (LCSH): | Bacteria, Ribosomes | |||||||||||||||
Journal or Publication Title: | Nature Communications | |||||||||||||||
Publisher: | Nature Publishing Group | |||||||||||||||
ISSN: | 2041-1723 | |||||||||||||||
Official Date: | 15 February 2018 | |||||||||||||||
Dates: |
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Volume: | 9 | |||||||||||||||
Number: | 1 | |||||||||||||||
Article Number: | 695 | |||||||||||||||
DOI: | 10.1038/s41467-018-02898-6 | |||||||||||||||
Status: | Peer Reviewed | |||||||||||||||
Publication Status: | Published | |||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||
Date of first compliant deposit: | 4 October 2018 | |||||||||||||||
Date of first compliant Open Access: | 4 October 2018 | |||||||||||||||
RIOXX Funder/Project Grant: |
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