Multiplexed characterization of rationally designed promoter architectures deconstructs combinatorial logic for IPTG-inducible systems

Timothy C. Yu, Winnie L. Liu, Marcia S. Brinck, Jessica E. Davis, Jeremy Shek, Grace Bower, Tal Einav, Kimberly D. Insigne, Rob Phillips, Sriram Kosuri () and Guillaume Urtecho ()
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Timothy C. Yu: University of California
Winnie L. Liu: University of California
Marcia S. Brinck: University of California
Jessica E. Davis: University of California
Jeremy Shek: University of California
Grace Bower: University of California
Tal Einav: California Institute of Technology
Kimberly D. Insigne: University of California
Rob Phillips: California Institute of Technology
Sriram Kosuri: University of California
Guillaume Urtecho: University of California

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract A crucial step towards engineering biological systems is the ability to precisely tune the genetic response to environmental stimuli. In the case of Escherichia coli inducible promoters, our incomplete understanding of the relationship between sequence composition and gene expression hinders our ability to predictably control transcriptional responses. Here, we profile the expression dynamics of 8269 rationally designed, IPTG-inducible promoters that collectively explore the individual and combinatorial effects of RNA polymerase and LacI repressor binding site strengths. We then fit a statistical mechanics model to measured expression that accurately models gene expression and reveals properties of theoretically optimal inducible promoters. Furthermore, we characterize three alternative promoter architectures and show that repositioning binding sites within promoters influences the types of combinatorial effects observed between promoter elements. In total, this approach enables us to deconstruct relationships between inducible promoter elements and discover practical insights for engineering inducible promoters with desirable characteristics.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20094-3

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DOI: 10.1038/s41467-020-20094-3

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