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Analysis of the simocyclinone biosynthesis ( sim ) gene cluster of  Streptomyces antibioticus  Tü6040 led to the identification of a putative pathway specific regulatory gene  simReg1 .  In silico  analysis places the SimReg1 protein in the OmpR-PhoB subfamily of response regulators. Gene replacement of  simReg1  from the  S. antibioticus  chromosome completely abolishes simocyclinone production indicating that SimReg1 is a key regulator of simocyclinone biosynthesis. Results of the DNA-shift assays and reporter gene expression analysis are consistent with the idea that SimReg1 activates transcription of simocyclinone biosynthesis, transporter genes, regulatory gene  simReg3  and his own transcription. The presence of extracts (simocyclinone) from  S. antibioticus  Tü6040  ×  pSSimR1-1 could dissociate SimReg1 from promoter regions. A preliminary model for regulation of simocyclinone biosynthesis and export is discussed.

SimReg1 is a master switch for biosynthesis and export of simocyclinone D8 and its precursors