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dc.contributor.authorMoser, Felix
dc.contributor.authorEspah Borujeni, Amin
dc.contributor.authorGhodasara, Amar Navin
dc.contributor.authorCameron, Douglas
dc.contributor.authorPark, YongJin
dc.contributor.authorVoigt, Christopher A.
dc.date.accessioned2019-03-29T19:41:50Z
dc.date.available2019-03-29T19:41:50Z
dc.date.issued2018-11
dc.identifier.issn1744-4292
dc.identifier.urihttp://hdl.handle.net/1721.1/121120
dc.description.abstractControlling gene expression during a bioprocess enables real-time metabolic control, coordinated cellular responses, and staging order-of-operations. Achieving this with small molecule inducers is impractical at scale and dynamic circuits are difficult to design. Here, we show that the same set of sensors can be integrated by different combinatorial logic circuits to vary when genes are turned on and off during growth. Three Escherichia coli sensors that respond to the consumption of feedstock (glucose), dissolved oxygen, and by-product accumulation (acetate) are constructed and optimized. By integrating these sensors, logic circuits implement temporal control over an 18-h period. The circuit outputs are used to regulate endogenous enzymes at the transcriptional and post-translational level using CRISPRi and targeted proteolysis, respectively. As a demonstration, two circuits are designed to control acetate production by matching their dynamics to when endogenous genes are expressed (pta or poxB) and respond by turning off the corresponding gene. This work demonstrates how simple circuits can be implemented to enable customizable dynamic gene regulation.en_US
dc.description.sponsorshipSynthetic Biology Engineering Research Center (SynBERC EEC0540879)en_US
dc.description.sponsorshipUnited States. Office of Naval Research. Multidisciplinary University Research Initiative (N00014‐13‐1‐0074)en_US
dc.description.sponsorshipUnited States. Department of Energy (DE‐SC0018368)en_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofhttp://dx.doi.org/10.15252/msb.20188605en_US
dc.rightsCreative Commons Attribution 4.0 International licenseen_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.sourceMolecular Systems Biologyen_US
dc.titleDynamic control of endogenous metabolism with combinatorial logic circuitsen_US
dc.typeArticleen_US
dc.identifier.citationMoser, Felix, Amin Espah Borujeni, Amar N. Ghodasara, Ewen Cameron, Yongjin Park, and Christopher A. Voigt. “Dynamic Control of Endogenous Metabolism with Combinatorial Logic Circuits.” Molecular Systems Biology 14, no. 11 (November 2018): e8605. © 2018 The Authorsen_US
dc.contributor.departmentInstitute for Medical Engineering and Scienceen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.mitauthorMoser, Felix
dc.contributor.mitauthorEspah Borujeni, Amin
dc.contributor.mitauthorGhodasara, Amar Navin
dc.contributor.mitauthorCameron, Douglas
dc.contributor.mitauthorPark, YongJin
dc.contributor.mitauthorVoigt, Christopher A.
dc.relation.journalMolecular Systems Biologyen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2019-02-28T14:26:11Z
dspace.orderedauthorsMoser, Felix; Espah Borujeni, Amin; Ghodasara, Amar N.; Cameron, Ewen; Park, Yongjin; Voigt, Christopher A.en_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0002-7762-3084
dc.identifier.orcidhttps://orcid.org/0000-0002-3036-7183
dc.identifier.orcidhttps://orcid.org/0000-0001-5409-1831
dc.identifier.orcidhttps://orcid.org/0000-0002-6788-2429
dc.identifier.orcidhttps://orcid.org/0000-0003-0844-4776
mit.licensePUBLISHER_CCen_US


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