ArticleNature chemical biology2018
Directed evolution of a synthetic phylogeny of programmable Trp repressors.
Article in Nature chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 72 citations in OpenAlex.
- Advances and perspectives in genetically encoded biosensors for biomarker detection and theranostic circuits.Synthetic and systems biotechnology · 2027Review
- Synthetic Biology of Plants and Microbes for Agriculture, Environment, and Future Applications.Chemical reviews · 2026Review
- Leveraging Autonomous Biological Oscillators for Directed Evolution of Switchable Proteins.Advances in experimental medicine and biology · 2026Review
- Directed Evolution in Escherichia coli for Novel Ligand-Binding Regulators: Evolving a Progesterone-Responsive Transcription Factor to Bind Cortisol.Current protocols · 2025Article
- Why cellular computations challenge our design principles.Seminars in cell & developmental biology · 2025Review
- Directed evolution of L-DOPA sensing and production enables efficient incorporation of an expanded genetic code into proteins.bioRxiv : the preprint server for biology · 2025Article
- Biological Switches: Past and Future Milestones of Transcription Factor-Based Biosensors.ACS synthetic biology · 2025Review
- Bacterial Metallostasis: Metal Sensing, Metalloproteome Remodeling, and Metal Trafficking.Chemical reviews · 2024Review
- Architecting a transcriptional repressor-based genetic inverter for tryptophan derived pathway regulation in Escherichia coli.Metabolic engineering · 2024Article
- Manipulating the molecular specificity of transcriptional biosensors for tryptophan metabolites and analogs.Cell reports. Physical science · 2024Article
- Accelerating Genetic Sensor Development, Scale-up, and Deployment Using Synthetic Biology.Biodesign research · 2024Article
- Advances in ligand-specific biosensing for structurally similar molecules.Cell systems · 2023Review
- Customizing cellular signal processing by synthetic multi-level regulatory circuits.Nature communications · 2023Review
- Divergent directed evolution of a TetR-type repressor towards aromatic molecules.Nucleic acids research · 2023Article
- Latent generative landscapes as maps of functional diversity in protein sequence space.Nature communications · 2023Article
- Transcription factor-based biosensors for screening and dynamic regulation.Frontiers in bioengineering and biotechnology · 2023Review
- Standardization of regulatory nodes for engineering heterologous gene expression: a feasibility study.Microbial biotechnology · 2022Article
- Engineering of a TrpR-Based Biosensor for Altered Dynamic Range and Ligand Preference.ACS synthetic biology · 2022Article
- A Versatile Transcription Factor Biosensor System Responsive to Multiple Aromatic and Indole Inducers.ACS synthetic biology · 2022Article
- Engineering of Synthetic Transcriptional Switches in Yeast.Life (Basel, Switzerland) · 2022Review
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3 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As synthetic regulatory programs expand in sophistication, an ever increasing number of biological components with predictable phenotypes is required. Regulators are often 'part mined' from a diverse, but uncharacterized, array of genomic sequences, often leading to idiosyncratic behavior. Here, we generate an entire synthetic phylogeny from the canonical allosteric transcription factor TrpR. Iterative rounds of positive and negative compartmentalized partnered replication (CPR) led to the exponential amplification of variants that responded with high affinity and specificity to halogenated tryptophan analogs and novel operator sites. Fourteen repressor variants were evolved with unique regulatory profiles across five operators and three ligands. The logic of individual repressors can be modularly programmed by creating heterodimeric fusions, resulting in single proteins that display logic functions, such as 'NAND'. Despite the evolutionarily limited regulatory role of TrpR, vast functional spaces exist around this highly conserved protein scaffold and can be harnessed to create synthetic regulatory programs.
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