Automated design of synthetic ribosome binding sites to control protein expression View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-10

AUTHORS

Howard M. Salis, Ethan A. Mirsky, Christopher A. Voigt

ABSTRACT

Microbial engineering often requires fine control over protein expression--for example, to connect genetic circuits or control flux through a metabolic pathway. To circumvent the need for trial and error optimization, we developed a predictive method for designing synthetic ribosome binding sites, enabling a rational control over the protein expression level. Experimental validation of >100 predictions in Escherichia coli showed that the method is accurate to within a factor of 2.3 over a range of 100,000-fold. The design method also correctly predicted that reusing identical ribosome binding site sequences in different genetic contexts can result in different protein expression levels. We demonstrate the method's utility by rationally optimizing protein expression to connect a genetic sensor to a synthetic circuit. The proposed forward engineering approach should accelerate the construction and systematic optimization of large genetic systems. More... »

PAGES

946-950

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nbt.1568

DOI

http://dx.doi.org/10.1038/nbt.1568

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1014210998

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19801975


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