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Related Concept Videos

Microbial Biosensors01:17

Microbial Biosensors

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Microbial biosensors are analytical devices that utilize living microbes to detect specific substances through measurable signals. These devices consist of two main components: biosensing organisms and signal-transducing elements. Biosensing organisms, such as Escherichia coli or Saccharomyces cerevisiae, are typically housed in multiwell plates connected to transducers, enabling rapid, real-time detection of target analytes.Signal Generation MechanismWhen a target analyte—such as...
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A general strategy to construct small molecule biosensors in eukaryotes.

Justin Feng1,2, Benjamin W Jester3,4, Christine E Tinberg5

  • 1Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, United States.

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Researchers developed a versatile biosensor technology using ligand-binding domains (LBDs) to detect small molecules. This method enables precise control of gene expression in various cell types, advancing metabolic engineering and synthetic biology applications.

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<i>a. thaliana</i><i>s. cerevisiae</i>CRISPRbiochemistrybiophysicsbiosensorshumanmetabolic engineeringstructural biology

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Area of Science:

  • Synthetic Biology
  • Molecular Biology
  • Biotechnology

Background:

  • Biosensors for small molecules are crucial for applications like metabolic engineering and transcriptional control.
  • Existing biosensor development can be limited in scope and applicability to diverse target molecules.

Purpose of the Study:

  • To develop a generalizable method for creating biosensors based on ligand-binding domains (LBDs) for various small molecules.
  • To demonstrate the utility of these biosensors in eukaryotic systems for applications in biotransformation and gene regulation.

Main Methods:

  • Engineered LBDs fused to fluorescent proteins or transcriptional activators.
  • Mutational destabilization of fusion proteins to ensure ligand-dependent accumulation.
  • Application in yeast, mammalian, and plant cells for transcriptional activation.

Main Results:

  • Successfully developed biosensors for digoxin and progesterone.
  • Achieved up to ~100-fold dynamic range in transcriptional activation upon ligand addition.
  • Demonstrated improved biotransformation of pregnenolone to progesterone in yeast.
  • Enabled ligand-inducible CRISPR activity regulation in mammalian cells.

Conclusions:

  • The presented methodology provides a broadly applicable strategy for biosensor development targeting diverse small molecules.
  • These engineered biosensors offer precise control over gene expression in multiple eukaryotic hosts.
  • This technology holds significant potential for advancing metabolic engineering, synthetic biology, and therapeutic applications.