ArticleNucleic acids research2019
Engineering repressors with coevolutionary cues facilitates toggle switches with a master reset.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- From codon optimization to AI-guided sequence design for engineered biological functions.Molecular therapy. Nucleic acids · 2026Article
- Engineered probiotics block arsenite absorption in the gastrointestinal tract.Trends in biotechnology · 2026Article
- Genetic Toolbox Expansion Enables Constitutively Fluorescent Lacticaseibacillus rhamnosus for Functional Microbiome Research.Microbial biotechnology · 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
- Engineered probiotics that sequester arsenite in a mouse gastrointestinal system.bioRxiv : the preprint server for biology · 2026Article
- Designing modular genetic sensors with TtgR/AcrR family transcriptional regulators by using a statistical and data-driven approach.Nucleic acids research · 2025Article
- A genetic safeguard for eliminating target genes in synthetic probiotics in a gut environment.iScience · 2025Article
- Thermal Adaptation of Cytosolic Malate Dehydrogenase Revealed by Deep Learning and Coevolutionary Analysis.Journal of chemical theory and computation · 2025Article
- Programming Nutrient Detection with Modular Regulators for Dynamic Control of Microbial Biosynthesis.ACS synthetic biology · 2025Article
- Biological Switches: Past and Future Milestones of Transcription Factor-Based Biosensors.ACS synthetic biology · 2025Review
- Sequence-Based Protein Design: A Review of Using Statistical Models to Characterize Coevolutionary Traits for Developing Hybrid Proteins as Genetic Sensors.International journal of molecular sciences · 2024Review
- Engineering Proteins Using Statistical Models of Coevolutionary Sequence Information.Cold Spring Harbor perspectives in biology · 2024Review
- Discovery of a high-performance phage-derived promoter/repressor system for probiotic lactobacillus engineering.Microbial cell factories · 2024Article
- Latent generative landscapes as maps of functional diversity in protein sequence space.Nature communications · 2023Article
- Computational compensatory mutation discovery approach: Predicting a PARP1 variant rescue mutation.Biophysical journal · 2022Article
- Design and engineering of allosteric communications in proteins.Current opinion in structural biology · 2022Review
- Coevolutionary methods enable robust design of modular repressors by reestablishing intra-protein interactions.Nature communications · 2021Article
- Substitutions at Nonconserved Rheostat Positions Modulate Function by Rewiring Long-Range, Dynamic Interactions.Molecular biology and evolution · 2021Article
- Protein conformations à la carte, a step further in de novo protein design.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Engineering allosteric transcriptional repressors containing an environmental sensing module (ESM) and a DNA recognition module (DRM) has the potential to unlock a combinatorial set of rationally designed biological responses. We demonstrated that constructing hybrid repressors by fusing distinct ESMs and DRMs provides a means to flexibly rewire genetic networks for complex signal processing. We have used coevolutionary traits among LacI homologs to develop a model for predicting compatibility between ESMs and DRMs. Our predictions accurately agree with the performance of 40 engineered repressors. We have harnessed this framework to develop a system of multiple toggle switches with a master OFF signal that produces a unique behavior: each engineered biological activity is switched to a stable ON state by different chemicals and returned to OFF in response to a common signal. One promising application of this design is to develop living diagnostics for monitoring multiple parameters in complex physiological environments and it represents one of many circuit topologies that can be explored with modular repressors designed with coevolutionary information.
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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.