title: SabR enhances nikkomycin production via regulating the transcriptional level of sanG, a pathway-specific regulatory gene in Streptomyces ansochromogenes.
abstract: BACKGROUND
  sabR is a pleiotropic regulatory gene which has been shown to positively regulate the nikkomycin biosynthesis and negatively affect the sporulation of Streptomyces ansochromogenes. In this study, we investigate the mechanism of SabR on modulating nikkomycin production in Streptomyces ansochromogenes.
  
  
  RESULTS
  The transcription start point of sabR was determined by high-resolution S1 nuclease mapping and localized at the nucleotide T at position 37 bp upstream of the potential sabR translation start codon (GTG). Disruption of sabR enhanced its own transcription, but retarded the nikkomycin production. Over-expression of sabR enhanced nikkomycin biosynthesis in Streptomyces ansochromogenes. EMSA analysis showed that SabR bound to the upstream region of sanG, but it did not bind to the upstream region of its encoding gene (sabR), sanF and the intergenic region between sanN and sanO. DNase 1 footprinting assays showed that the SabR-binding site upstream of sanG was 5'-CTTTAAGTCACCTGGCTCATTCGCGTTCGCCCAGCT-3' which was designated as SARE. Deletion of SARE resulted in the delay of nikkomycin production that was similar to that of sabR disruption mutant.
  
  
  CONCLUSIONS
  These results indicated that SabR modulated nikkomycin biosynthesis as an enhancer via interaction with the promoter region of sanG, and expanded our understanding about regulatory cascade in nikkomycin biosynthesis.
authors.affiliation: The Key Laboratory of Systematic Mycology and Lichenology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Pan
authors.forename: Linqi
authors.initials: L
authors.lastname: Wang
authors.forename: Xihong
authors.initials: X
authors.lastname: He
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Tian
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Huarong
authors.initials: H
authors.lastname: Tan
mesh_terms: D000617:Aminoglycosides / Q000096:biosynthesis*; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D018983:DNA Footprinting; D004269:DNA, Bacterial / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005656:Fungal Proteins / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D055786:Gene Knockout Techniques; D008969:Molecular Sequence Data; D011485:Protein Binding; D015719:Single-Strand Specific DNA and RNA Endonucleases / Q000378:metabolism; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D005656:Fungal Proteins; D014157:Transcription Factors; C011952:nikkomycin; C526098:Endonuclease S1, Aspergillus; D015719:Single-Strand Specific DNA and RNA Endonucleases