Open Access Original

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

Liliya Horbal1, Yuriy Rebets1, Mariya Rabyk1, Roman Makitrynskyy1, Andriy Luzhetskyy2, Victor Fedorenko1 and Andreas Bechthold3*

Author Affiliations

1 Department of Genetics and Biotechnology of Ivan Franko National University of L'viv, Grushevskogo st.4, L'viv 79005, Ukraine

2 Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infectious Research (HZI), Department Microbial Natural Products Actinobacteria, Metabolic Engineering Group, Saarland University, Campus C2 3 66123 Saarbrücken, Germany

3 Institut für Pharmazeutische Wissenschaften, Lehrstuhl für Pharmazeutische Biologie und Biotechnologie, Albert-Ludwigs-Universität Freiburg, Stefan-Meier-Strasse 19, 79104 Freiburg, Germany

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AMB Express 2012, 2:1  doi:10.1186/2191-0855-2-1

Published: 3 January 2012

Abstract

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.

Keywords:
Simocyclinone; angucycline; regulation; transport