RT Journal Article
SR Electronic
T1 Dynamic allocation of orthogonal ribosomes facilitates uncoupling of co-expressed genes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 138362
DO 10.1101/138362
A1 Alexander P.S. Darlington
A1 Juhyun Kim
A1 José I. Jiménez
A1 Declan G. Bates
YR 2017
UL http://biorxiv.org/content/early/2017/05/16/138362.abstract
AB Introduction of synthetic circuits into host microbes creates competition between circuit and host genes for shared cellular resources, such as RNA polymerases and ribosomes. This can lead to the emergence of unwanted coupling between the expression of different genes, complicating circuit design and potentially leading to circuit failure. Here we demonstrate the ability of orthogonal ribosomes to alleviate the effects of this resource competition. We partition the ribosome pool by expressing an engineered 16S RNA with altered specificity, and use this division of specificity to build simple resource allocators which reduce the level of ribosome-mediated gene coupling. We then design and implement a dynamic resource allocation controller, which acts to increase orthogonal ribosome production as the demand for translational resources by a synthetic circuit increases. Our results highlight the potential of dynamic translational resource allocation as a means of minimising the impact of cellular limitations on the function of synthetic circuitry.