ArticleProceedings of the National Academy of Sciences of the United States of America2016
Genetically encoded sensors enable real-time observation of metabolite production.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed.
- Advances and perspectives in genetically encoded biosensors for biomarker detection and theranostic circuits.Synthetic and systems biotechnology · 2027Review
- Engineering microbial consortia for distributed signal processing.Nature communications · 2026Article
- Establishing Saccharomyces cerevisiae as a host for renewable acrylic acid production.Microbial cell factories · 2026Article
- Computational design of allulose-responsive biosensor toolbox for auto-inducible protein expression and CRISPRi mediated dynamic metabolic regulation.Nature communications · 2025Article
- Disentangling Metabolite Detection from Pathway Stress Using Biosensors.ACS synthetic biology · 2025Article
- Directed Evolution of Branched-Chain α-Keto Acid Decarboxylase for 3-Hydroxypropionic Acid Production inACS synthetic biology · 2025Article
- Engineering an Overflow-Responsive Regulation System for Balancing Cellular Redox and Optimizing Microbial Production.Biotechnology and bioengineering · 2025Article
- Computation-guided transcription factor biosensor specificity engineering for adipic acid detection.Computational and structural biotechnology journal · 2024Article
- Genetically encoded biosensors for the circular plastics bioeconomy.Metabolic engineering communications · 2024Article
- Architecting a transcriptional repressor-based genetic inverter for tryptophan derived pathway regulation in Escherichia coli.Metabolic engineering · 2024Article
- Cell factories for biosynthesis of D-glucaric acid: a fusion of static and dynamic strategies.World journal of microbiology & biotechnology · 2024Review
- AI-Assisted Rational Design and Activity Prediction of Biological Elements for Optimizing Transcription-Factor-Based Biosensors.Molecules (Basel, Switzerland) · 2024Review
- Enhancing glucaric acid production fromApplied and environmental microbiology · 2024Article
- State-of-the-art in engineering small molecule biosensors and their applications in metabolic engineering.SLAS technology · 2024Review
- Production of D-glucaric acid with phosphoglucose isomerase-deficient Saccharomyces cerevisiae.Biotechnology letters · 2024Article
- Genetically Encoded Biosensor Engineering for Application in Directed Evolution.Journal of microbiology and biotechnology · 2023Review
- Identifying, Characterizing, and Engineering a Phenolic Acid-Responsive Transcriptional Factor fromACS synthetic biology · 2023Article
- TFBMiner: A User-Friendly Command Line Tool for the Rapid Mining of Transcription Factor-Based Biosensors.ACS synthetic biology · 2023Article
- Applications and Tuning Strategies for Transcription Factor-Based Metabolite Biosensors.Biosensors · 2023Review
- Development and Application of Whole-Cell Biosensors for the Detection of Gallic Acid.ACS synthetic biology · 2023Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Engineering cells to produce valuable metabolic products is hindered by the slow and laborious methods available for evaluating product concentration. Consequently, many designs go unevaluated, and the dynamics of product formation over time go unobserved. In this work, we develop a framework for observing product formation in real time without the need for sample preparation or laborious analytical methods. We use genetically encoded biosensors derived from small-molecule responsive transcription factors to provide a fluorescent readout that is proportional to the intracellular concentration of a target metabolite. Combining an appropriate biosensor with cells designed to produce a metabolic product allows us to track product formation by observing fluorescence. With individual cells exhibiting fluorescent intensities proportional to the amount of metabolite they produce, high-throughput methods can be used to rank the quality of genetic variants or production conditions. We observe production of several renewable plastic precursors with fluorescent readouts and demonstrate that higher fluorescence is indeed an indicator of higher product titer. Using fluorescence as a guide, we identify process parameters that produce 3-hydroxypropionate at 4.2 g/L, 23-fold higher than previously reported. We also report, to our knowledge, the first engineered route from glucose to acrylate, a plastic precursor with global sales of $14 billion. Finally, we monitor the production of glucarate, a replacement for environmentally damaging detergents, and muconate, a renewable precursor to polyethylene terephthalate and nylon with combined markets of $51 billion, in real time, demonstrating that our method is applicable to a wide range of molecules.
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