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Programming mRNA decay to modulate synthetic circuit resource allocation

Author

Listed:
  • Ophelia S. Venturelli

    (California Institute for Quantitative Biosciences, University of California Berkeley
    University of California Berkeley)

  • Mika Tei

    (California Institute for Quantitative Biosciences, University of California Berkeley
    University of California Berkeley)

  • Stefan Bauer

    (Energy Biosciences Institute, University of California Berkeley)

  • Leanne Jade G. Chan

    (Lawrence Berkeley National Laboratory)

  • Christopher J. Petzold

    (Lawrence Berkeley National Laboratory)

  • Adam P Arkin

    (California Institute for Quantitative Biosciences, University of California Berkeley
    University of California Berkeley
    Energy Biosciences Institute, University of California Berkeley
    Environmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory)

Abstract

Synthetic circuits embedded in host cells compete with cellular processes for limited intracellular resources. Here we show how funnelling 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. Altogether, our results suggest that manipulation of cellular resource allocation is a key control parameter for synthetic circuit design.

Suggested Citation

  • Ophelia S. Venturelli & Mika Tei & Stefan Bauer & Leanne Jade G. Chan & Christopher J. Petzold & Adam P Arkin, 2017. "Programming mRNA decay to modulate synthetic circuit resource allocation," Nature Communications, Nature, vol. 8(1), pages 1-11, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15128
    DOI: 10.1038/ncomms15128
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