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Metagenomic mining of regulatory elements enables programmable species-selective gene expression.


ABSTRACT: Robust and predictably performing synthetic circuits rely on the use of well-characterized regulatory parts across different genetic backgrounds and environmental contexts. Here we report the large-scale metagenomic mining of thousands of natural 5' regulatory sequences from diverse bacteria, and their multiplexed gene expression characterization in industrially relevant microbes. We identified sequences with broad and host-specific expression properties that are robust in various growth conditions. We also observed substantial differences between species in terms of their capacity to utilize exogenous regulatory sequences. Finally, we demonstrate programmable species-selective gene expression that produces distinct and diverse output patterns in different microbes. Together, these findings provide a rich resource of characterized natural regulatory sequences and a framework that can be used to engineer synthetic gene circuits with unique and tunable cross-species functionality and properties, and also suggest the prospect of ultimately engineering complex behaviors at the community level.

SUBMITTER: Johns NI 

PROVIDER: S-EPMC6065261 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Metagenomic mining of regulatory elements enables programmable species-selective gene expression.

Johns Nathan I NI   Gomes Antonio L C ALC   Yim Sung Sun SS   Yang Anthony A   Blazejewski Tomasz T   Smillie Christopher S CS   Smith Mark B MB   Alm Eric J EJ   Kosuri Sriram S   Wang Harris H HH  

Nature methods 20180319 5


Robust and predictably performing synthetic circuits rely on the use of well-characterized regulatory parts across different genetic backgrounds and environmental contexts. Here we report the large-scale metagenomic mining of thousands of natural 5' regulatory sequences from diverse bacteria, and their multiplexed gene expression characterization in industrially relevant microbes. We identified sequences with broad and host-specific expression properties that are robust in various growth conditi  ...[more]

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