ArticleNucleic acids research2016
Post-translational control of genetic circuits using Potyvirus proteases.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 87 citations in OpenAlex.
- Directed evolution of functional intrinsically disordered proteins.Nature chemical biology · 2026Article
- Identification and engineering of highly functional potyviral proteases in cells using co-evolutionary models.Nature communications · 2026Article
- Synthetic Biology of Plants and Microbes for Agriculture, Environment, and Future Applications.Chemical reviews · 2026Review
- A programmable genetic platform for engineering noninvasive biosensors.Science advances · 2026Article
- High-Throughput Activity Reprogramming of Proteases (HARP).ACS chemical biology · 2025Article
- A programmable genetic platform for engineering noninvasive biosensors.bioRxiv : the preprint server for biology · 2025Article
- De novo designed protein guiding targeted protein degradation.Nature communications · 2025Article
- PERRC: Protease Engineering with Reactant Residence Time Control.ACS synthetic biology · 2025Article
- A generalizable approach for programming protease-responsive conformationally inhibited artificial transcriptional factors.Nature communications · 2025Article
- Engineering a New SsrA-Based Degradation Tag (LAA-LAA) and a Bacterial Synthetic Oscillator.ACS synthetic biology · 2025Article
- Exploring the potential of water channels for developing genetically encoded reporters and biosensors for diffusion-weighted MRI.Journal of magnetic resonance (San Diego, Calif. : 1997) · 2024Article
- State-of-the-art in engineering small molecule biosensors and their applications in metabolic engineering.SLAS technology · 2024Review
- Synthetic Biology Meets CaCells · 2024Review
- A single-component, light-assisted uncaging switch for endoproteolytic release.Nature chemical biology · 2024Article
- Exploring the potential of water channels for developing MRI reporters and sensors without the need for exogenous contrast agents.bioRxiv : the preprint server for biology · 2024Article
- Accelerating Genetic Sensor Development, Scale-up, and Deployment Using Synthetic Biology.Biodesign research · 2024Article
- An Intelligent Synthetic Bacterium for Chronological Toxicant Detection, Biodegradation, and Its Subsequent Suicide.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Dissecting the Determinants of Domain Insertion Tolerance and Allostery in Proteins.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Enabling technology and core theory of synthetic biology.Science China. Life sciences · 2023Review
- A synthetic population-level oscillator in non-microfluidic environments.Communications biology · 2023Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetic engineering projects often require control over when a protein is degraded. To this end, we use a fusion between a degron and an inactivating peptide that can be added to the N-terminus of a protein. When the corresponding protease is expressed, it cleaves the peptide and the protein is degraded. Three protease:cleavage site pairs from Potyvirus are shown to be orthogonal and active in exposing degrons, releasing inhibitory domains and cleaving polyproteins. This toolbox is applied to the design of genetic circuits as a means to control regulator activity and degradation. First, we demonstrate that a gate can be constructed by constitutively expressing an inactivated repressor and having an input promoter drive the expression of the protease. It is also shown that the proteolytic release of an inhibitory domain can improve the dynamic range of a transcriptional gate (200-fold repression). Next, we design polyproteins containing multiple repressors and show that their cleavage can be used to control multiple outputs. Finally, we demonstrate that the dynamic range of an output can be improved (8-fold to 190-fold) with the addition of a protease-cleaved degron. Thus, controllable proteolysis offers a powerful tool for modulating and expanding the function of synthetic gene circuits.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.