Design, development and application of whole-cell based antibiotic-specific biosensor
| Autor: | Stepan Tistechok, Andriy Luzhetskyy, Stefan Schmelz, Oleksandr Gromyko, Lutz Petzke, Andrea Scrima, Yuriy Rebets |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Computer science 030106 microbiology technology industry and agriculture Bioengineering macromolecular substances Computational biology Biosensing Techniques Applied Microbiology and Biotechnology Streptomyces 03 medical and health sciences Polyketide Synthetic biology chemistry.chemical_compound 030104 developmental biology chemistry Transcriptional Repressor TetR Macrolides Microorganisms Genetically-Modified Whole cell Biosensor Biotechnology |
| Zdroj: | Metabolic engineering. 47 |
| ISSN: | 1096-7184 |
| Popis: | Synthetic biology techniques hold great promise for optimising the production of natural products by microorganisms. However, evaluating the phenotype of a modified bacterium represents a major bottleneck to the engineering cycle - particularly for antibiotic-producing actinobacteria strains, which grow slowly and are challenging to genetically manipulate. Here, we report the generation and application of antibiotic-specific whole-cell biosensor derived from TetR transcriptional repressor for use in identifying and optimising antibiotic producers. The constructed biosensor was successfully used to improve production of polyketide antibiotic pamamycin. However, an initial biosensor based on native genetic elements had inadequate dynamic and operating ranges. To overcome these limitations, we fine-tuned biosensor performance through alterations of the promoter and operator of output module and the ligand affinity of transcription factor module, which enabled us to deduce recommendations for building and application of actinobacterial biosensors. |
| Databáze: | OpenAIRE |
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