Macrolide Biosensor Optimization through Cellular Substrate Sequestration
| Autor: | Sydney E Parks, Corwin Miller, Matthew R. Bennett, Joanne M. L. Ho |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0106 biological sciences
Letter Biomedical Engineering Gene Expression macromolecular substances Biosensing Techniques medicine.disease_cause 01 natural sciences Biochemistry Genetics and Molecular Biology (miscellaneous) Metabolic engineering 03 medical and health sciences Synthetic biology 010608 biotechnology Drug Resistance Bacterial medicine Escherichia coli Phosphorylation 030304 developmental biology 0303 health sciences Chemistry Escherichia coli Proteins technology industry and agriculture Substrate (chemistry) General Medicine Gene Expression Regulation Bacterial Anti-Bacterial Agents Erythromycin Drug development Metabolic Engineering Biophysics Synthetic Biology Biosensor Intracellular Transcription Factors |
| Zdroj: | ACS Synthetic Biology |
| ISSN: | 2161-5063 |
| Popis: | Developing and optimizing small-molecule biosensors is a central goal of synthetic biology. Here we incorporate additional cellular components to improve biosensor sensitivity by preventing target molecules from diffusing out of cells. We demonstrate that trapping erythromycin within Escherichia coli through phosphorylation increases the sensitivity of its biosensor (MphR) by approximately 10-fold. When combined with prior engineering efforts, our optimized biosensor can detect erythromycin concentrations as low as 13 nM. We show that this strategy works with a range of macrolide substrates, enabling the potential usage of our optimized system for drug development and metabolic engineering. This strategy can be extended in future studies to improve the sensitivity of other biosensors. Our findings further suggest that many naturally evolved genes involved in resistance to multiple classes of antibiotics may increase intracellular drug concentrations to modulate their own expression, acting as a form of regulatory feedback. |
| Databáze: | OpenAIRE |
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