@article{3730,
  keywords = {Gene Expression Regulation, Bacterial, Escherichia coli, Anti-Bacterial Agents, Mutagenesis, Transcription Factors, Multigene Family, Phenotype, Saccharomyces cerevisiae, Biological Products, Burkholderia, DNA Transposable Elements, Genome, Bacterial, Secondary Metabolism, Polyenes, Polyketide Synthases},
  author = {Jong-Duk Park and Kyuho Moon and Cheryl Miller and Jessica Rose and Fei Xu and Christopher Ebmeier and Jeremy Jacobsen and Dainan Mao and William Old and David DeShazer and Mohammad Seyedsayamdost},
  title = {Thailandenes, Cryptic Polyene Natural Products Isolated from  Using Phenotype-Guided Transposon Mutagenesis.},
  abstract = { <p> has emerged as a model organism for investigating the production and regulation of diverse secondary metabolites. Most of the biosynthetic gene clusters encoded in  are silent, motivating the development of new methods for accessing their products. In the current work, we add to the canon of available approaches using phenotype-guided transposon mutagenesis to characterize a silent biosynthetic gene cluster. Because secondary metabolite biosynthesis is often associated with phenotypic changes, we carried out random transposon mutagenesis followed by phenotypic inspection of the resulting colonies. Several mutants exhibited intense pigmentation and enhanced expression of an iterative type I polyketide synthase cluster that we term . Disruptions of , , and  abolished the biosynthesis of the diffusible pigment, thus linking it to the  operon. Isolation and structural elucidation by HR-MS and 1D/2D NMR spectroscopy revealed three novel, cryptic metabolites, thailandene A-C. Thailandenes are linear formylated or acidic polyenes containing a combination of  and  double bonds. Variants A and B exhibited potent antibiotic activity against  and  but not against . One of the transposon mutants that exhibited an enhanced expression of  contained an insertion upstream of a σ54-dependent transcription factor. Closer inspection of the  operon uncovered a σ54 promoter consensus sequence upstream of , providing clues regarding its regulation. Our results showcase the utility of phenotype-guided transposon mutagenesis in uncovering cryptic metabolites encoded in bacterial genomes.</p> },
  year = {2020},
  journal = {ACS Chem Biol},
  volume = {15},
  pages = {1195-1203},
  month = {2020 May 15},
  issn = {1554-8937},
  doi = {10.1021/acschembio.9b00883},
  language = {eng},
}