期刊
NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-02898-6
关键词
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资金
- University of Warwick
- EPSRC & BBSRC Centre for Doctoral Training in Synthetic Biology [EP/L016494/1]
- European Union's Horizon research and innovation programme [633962]
- Biotechnology and Biological Sciences Research Council (BBSRC) [BB/M009769/1]
- Biotechnology and Biological Sciences Research Council [BB/M017982/1, BB/M009769/1] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [1500841] Funding Source: researchfish
- BBSRC [BB/M009769/1, BB/M017982/1] Funding Source: UKRI
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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