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Time-series transcriptional profiling of MazF-induced E. coli populations

ABSTRACT: Synthetic circuits embedded in host-cells compete with cellular processes for limited intracellular resources. We show how funneling of cellular resources, after global transcriptome degradation by the sequence-dependent endoribonuclease MazF, to a synthetic circuit can increase production. Target genes are protected from MazF activity by recoding the gene sequence to eliminate recognition sites, while preserving the amino acid sequence. The expression of a protected fluorescent reporter and flux of a high-value metabolite are significantly enhanced using this genome-scale control strategy. Proteomics measurements discover a host factor in need of protection to improve resource redistribution activity. A computational model demonstrates that the MazF mRNA-decay feedback loop enables proportional control of MazF in an optimal operating regime. Transcriptional profiling of MazF-induced cells elucidates the dynamic shifts in transcript abundance and discovers regulatory design elements. Together, our results suggest that manipulation of cellular resource allocation is a key control parameter for synthetic circuit design.

ORGANISM(S): Escherichia coli K-12

PROVIDER: GSE94998 | GEO | 2017/04/15

SECONDARY ACCESSION(S): PRJNA375104

REPOSITORIES: GEO

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Time-series transcriptional profiling of MazF-induced E. coli populations

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