ArticleACS synthetic biology2018
Development of Transcription Factor-Based Designer Macrolide Biosensors for Metabolic Engineering and Synthetic Biology.
Article in ACS synthetic biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 95 citations in OpenAlex.
- Translating biosynthetic gene cluster architecture into biosensor design for microbial natural product discovery.Essays in biochemistry · 2026Review
- A double-layer plate method for rapid screening of cell wall-targeting antibiotic producers using a microbial whole-cell biosensor.Applied and environmental microbiology · 2026Article
- The Fragmented Nature of Biosensor Development: Challenges and Paths to Mitigation.Biosensors · 2026Review
- Development of a transcription factor-based biosensor strain for reporting α-terpineol productionRSC chemical biology · 2026Article
- Synthetic Biology of Plants and Microbes for Agriculture, Environment, and Future Applications.Chemical reviews · 2026Review
- Efflux pump knockout minimizes crosstalk and boosts response in transcription factor-based biosensors.Journal of biological engineering · 2025Article
- Directed Evolution of a Macrolide-Sensing Transcription Factor Biosensor for the Detection of Macrolactone Aglycones via "Effector Walking" and Efflux Pump Deletion.Biochemistry · 2025Article
- Microbial Transcription Factor-Based Biosensors: Innovations from Design to Applications in Synthetic Biology.Biosensors · 2025Review
- Refactoring the pikromycin synthase for the modular biosynthesis of macrolide antibiotics in E. coli.Research square · 2025Article
- AI-Assisted Rational Design and Activity Prediction of Biological Elements for Optimizing Transcription-Factor-Based Biosensors.Molecules (Basel, Switzerland) · 2024Review
- State-of-the-art in engineering small molecule biosensors and their applications in metabolic engineering.SLAS technology · 2024Review
- Advances in ligand-specific biosensing for structurally similar molecules.Cell systems · 2023Review
- Biosensor Guided Polyketide Synthases Engineering for Optimization of Domain Exchange Boundaries.Nature communications · 2023Article
- Advances in Synthetic-Biology-Based Whole-Cell Biosensors: Principles, Genetic Modules, and Applications in Food Safety.International journal of molecular sciences · 2023Review
- Applications and Tuning Strategies for Transcription Factor-Based Metabolite Biosensors.Biosensors · 2023Review
- Biosensor development for single-cell detection of glucuronate.Journal of industrial microbiology & biotechnology · 2023Article
- Olfactory Receptors as an Emerging Chemical Sensing Scaffold.Biochemistry · 2023Review
- Review
- Striving for sustainable biosynthesis: discovery, diversification, and production of antimicrobial drugs in Escherichia coli.Biochemical Society transactions · 2022Review
- Development of Whole-Cell Biosensors for Screening of Peptidoglycan-Targeting Antibiotics in a Gram-Negative Bacterium.Applied and environmental microbiology · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Macrolides are a large group of natural products that display broad and potent biological activities and are biosynthesized by type I polyketide synthases (PKSs) and associated enzymatic machinery. There is an urgent need to access macrolides and unnatural macrolide derivatives for drug discovery, drug manufacture, and probe development. Typically, efforts to engineer the biosynthesis of macrolides and macrolide analogues in various microbial hosts are hampered by the complexity of macrolide biosynthetic pathways and our limited ability to rationally reprogram type I PKSs and post-PKS machinery. High-throughput approaches based on synthetic biology and directed evolution could overcome this problem by testing the function of large libraries of variants. Yet, methods that can identify mutant enzymes, pathways, and strains that produce the desired macrolide target are not generally available. Here we show that the promiscuous macrolide sensing transcription factor MphR is a powerful platform for engineering variants with tailored properties. We identified variants that displayed improved sensitivity toward erythromycin, tailored the inducer specificity, and significantly improved sensitivity to macrolides that were very poor inducers of the wild-type MphR biosensor. Designer macrolide biosensors should find broad utility and enable applications related to high-throughput synthetic biology and directed evolution of macrolide biosynthesis.
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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.