Automated model-predictive design of synthetic promoters to control transcriptional profiles in bacteria.

Nat Commun

Department of Chemical Engineering, Pennsylvania State University, University Park, PA, 16801, USA.

Published: September 2022

Transcription rates are regulated by the interactions between RNA polymerase, sigma factor, and promoter DNA sequences in bacteria. However, it remains unclear how non-canonical sequence motifs collectively control transcription rates. Here, we combine massively parallel assays, biophysics, and machine learning to develop a 346-parameter model that predicts site-specific transcription initiation rates for any σ promoter sequence, validated across 22132 bacterial promoters with diverse sequences. We apply the model to predict genetic context effects, design σ promoters with desired transcription rates, and identify undesired promoters inside engineered genetic systems. The model provides a biophysical basis for understanding gene regulation in natural genetic systems and precise transcriptional control for engineering synthetic genetic systems.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9440211PMC
http://dx.doi.org/10.1038/s41467-022-32829-5DOI Listing

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