Design, development and application of whole-cell based antibiotic-specific biosensor.

Metab Eng

Universität des Saarlandes, Pharmazeutische Biotechnologie, Bld. C2.3, 66123 Saarbrücken, Germany; Helmholtz-Institute for Pharmaceutical Research Saarland, UdS Campus, Bld. E8.1, 66123 Saarbrücken, Germany. Electronic address:

Published: May 2018

AI Article Synopsis

  • Synthetic biology can enhance how microorganisms produce natural products, but assessing modified bacteria, especially slow-growing actinobacteria, is a major challenge in the engineering process.* -
  • The study introduced an antibiotic-specific whole-cell biosensor based on a TetR repressor to identify and optimize antibiotic-producing bacteria, successfully improving pamamycin production.* -
  • Initial biosensor designs lacked effectiveness, so researchers adjusted components like promoters and ligands, leading to better performance and guidelines for developing future actinobacterial biosensors.*

Article Abstract

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.

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Source
http://dx.doi.org/10.1016/j.ymben.2018.03.019DOI Listing

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