Metalloprotein switches that display chemical-dependent electron transfer in cells

Joshua T. Atkinson, Ian J. Campbell, Emily E. Thomas, Sheila C. Bonitatibus, Sean J. Elliott, George N. Bennett, Jonathan J. Silberg

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Biological electron transfer is challenging to directly regulate using environmental conditions. To enable dynamic, protein-level control over energy flow in metabolic systems for synthetic biology and bioelectronics, we created ferredoxin logic gates that utilize transcriptional and post-translational inputs to control energy flow through a synthetic electron transfer pathway that is required for bacterial growth. These logic gates were created by subjecting a thermostable, plant-type ferredoxin to backbone fission and fusing the resulting fragments to a pair of proteins that self-associate, a pair of proteins whose association is stabilized by a small molecule, and to the termini of a ligand-binding domain. We show that the latter domain insertion design strategy yields an allosteric ferredoxin switch that acquires an oxygen-tolerant [2Fe–2S] cluster and can use different chemicals, including a therapeutic drug and an environmental pollutant, to control the production of a reduced metabolite in Escherichia coli and cell lysates.

Original languageEnglish (US)
Pages (from-to)189-195
Number of pages7
JournalNature Chemical Biology
Volume15
Issue number2
DOIs
StatePublished - Feb 1 2019
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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