Dynamic allocation of orthogonal ribosomes facilitates uncoupling of co-expressed genes.
Dynamic allocation of orthogonal ribosomes facilitates uncoupling of co-expressed genes.
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DOI：
10.1038/s41467-018-02898-6
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发表时间：
2018-02-15
影响因子：
16.6
通讯作者：
Bates DG
中科院分区：
文献类型：
--
作者：
Darlington APS;Kim J;Jiménez JI;Bates DG
将合成电路引入微生物中会在电路和宿主基因之间产生竞争，以共享细胞资源，如核糖体。这可能导致不同电路基因的表达之间出现不必要的耦合，使设计过程复杂化，并可能导致电路故障。通过表达具有改变的特异性的合成16S rRNA，我们可以将核糖体池划分为宿主特异性和电路特异性活动。我们的数学和实验表明，资源竞争的影响可以减轻靶向基因不同的核糖体池。这种劳动分工可用于增加通过代谢途径的通量。我们开发了一个细胞生理学模型，它能够捕获这些观察，并使用它来设计一个动态的资源分配控制器。当实施时，该控制器通过增加正交核糖体生产来解耦基因，因为合成电路对翻译资源的需求增加。合成遗传电路和宿主基因之间对共享资源的竞争可能会使电路设计复杂化并导致失败。在这里，作者通过数学和实验证明了正交核糖体的使用可以解耦竞争基因。
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. Competition between synthetic genetic circuits and host genes for shared resources can complicate circuit design and lead to failure. Here the authors demonstrate, mathematically and experimentally, the use of orthogonal ribosomes to decouple competing genes.
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影响因子：
14.9
作者：
Chubiz LM;Rao CV
通讯作者：
Rao CV
DOI：
10.1099/mic.0.067975-0
发表时间：
2013-07
期刊：
Microbiology (Reading, England)
影响因子：
--
作者：
Arpino JAJ;Hancock EJ;Anderson J;Barahona M;Stan GV;Papachristodoulou A;Polizzi K
通讯作者：
Polizzi K
影响因子：
48
作者：
Gibson, Daniel G.;Young, Lei;Smith, Hamilton O.
通讯作者：
Smith, Hamilton O.
大肠杆菌K-12的构造框架，单基因敲除突变体：Keio Collection。
影响因子：
9.9
作者：
通讯作者：
--
影响因子：
16.6
作者：
Kushwaha M;Salis HM
通讯作者：
Salis HM