The biosynthesis of antibiotics is controlled by cascade regulation involving cluster-situated regulators (CSRs) and pleiotropic regulators. Three CSRs have been identified in the jadomycin biosynthetic gene cluster, including one OmpR-type activator (JadR1) and two TetR-like repressors (JadR and JadR2). To examine their interactions in jadomycin biosynthesis, a series of mutants were generated and tested for jadomycin production. We noticed that jadomycin production in the jadR-jadR2 double mutant was increased dramatically compared with either single mutant. Transcriptional analysis showed that jadR and jadR2 act synergistically to repress jadomycin production by inhibiting the transcription of jadR1. Furthermore, jadR and jadR2 reciprocally inhibit each other. The complex interactions among these three CSRs may provide clues for the activation of the jadomycin gene cluster, which would otherwise remain silent without stimulation from stress signals.
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http://dx.doi.org/10.1007/s11427-013-4508-y | DOI Listing |
Sci China Life Sci
July 2013
State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
The biosynthesis of antibiotics is controlled by cascade regulation involving cluster-situated regulators (CSRs) and pleiotropic regulators. Three CSRs have been identified in the jadomycin biosynthetic gene cluster, including one OmpR-type activator (JadR1) and two TetR-like repressors (JadR and JadR2). To examine their interactions in jadomycin biosynthesis, a series of mutants were generated and tested for jadomycin production.
View Article and Find Full Text PDFMicrobiology (Reading)
August 2003
Department of Biology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4J1.
Three new genes (jadW(1), jadW(2) and jadW(3)) were isolated from a region of the Streptomyces venezuelae ISP5230 chromosome at the left-hand end of the jad cluster for jadomycin B (JdB) biosynthesis. The deduced amino acid sequence of jadW(1) showed strong similarity to gene products associated in several streptomycetes with gamma-butyrolactone autoregulators controlling morphological differentiation and secondary metabolism. Examination of JadW(1) for conserved domains detected a repeat sequence characteristic of proteins in the AfsA regulatory family.
View Article and Find Full Text PDFGene
November 2001
Department of Biology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4J1.
A second regulatory gene (jadR(1)) is located immediately upstream of the putative repressor gene (jadR(2)) in the jad cluster for biosynthesis of the antibiotic jadomycin B in Streptomyces venezuelae ISP5230. It encodes a 234-amino acid polypeptide with a sequence resembling those of response regulator proteins in two-component control systems. Features in the conserved C-terminal domain of JadR(1) place the protein in the OmpR-PhoB subfamily of response regulators.
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