• Open Access

Deletion of the signalling molecule synthase ScbA has pleiotropic effects on secondary metabolite biosynthesis, morphological differentiation and primary metabolism in Streptomyces coelicolor A3(2)

Authors

  • Davide D'Alia,

    1. Department of Microbial Physiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Haren, the Netherlands
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  • Daniela Eggle,

    1. Center for Bioinformatics Tübingen, Department of Information and Cognitive Sciences, University of Tübingen, Tübingen, Germany
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    • Present address: Pharma Research Scientific Informatics, In Silico Sciences- Bioinformatics, Roche Diagnostics GmbH, Pharma Research Penzberg, Penzberg, Germany.

  • Kay Nieselt,

    1. Center for Bioinformatics Tübingen, Department of Information and Cognitive Sciences, University of Tübingen, Tübingen, Germany
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  • Wei-Shou Hu,

    1. Department of Chemical Engineering and Material Science, University of Minnesota, Minneapolis, MN, USA
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  • Rainer Breitling,

    1. Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
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  • Eriko Takano

    Corresponding author
    1. Department of Microbial Physiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Haren, the Netherlands
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E-mail e.takano@rug.nl; Tel. (+31) 50 3632143; Fax (+31) 50 3632154.

Summary

Streptomycetes have high biotechnological relevance as producers of diverse metabolites widely used in medical and agricultural applications. The biosynthesis of these metabolites is controlled by signalling molecules, γ-butyrolactones, that act as bacterial hormones. In Streptomyces coelicolor, a group of signalling molecules called SCBs (S. coelicolorbutanolides) regulates production of the pigmented antibiotics coelicolor polyketide (CPK), actinorhodin and undecylprodigiosin. The γ-butyrolactone synthase ScbA is responsible for the biosynthesis of SCBs. Here we show the results of a genome-wide transcriptome analysis of a scbA deletion mutant prior to and during the transition to antibiotic production. We report a strong perturbation in the expression of three pigmented antibiotic clusters in the mutant throughout the growth curve, thus providing a molecular explanation for the antibiotic phenotype observed previously. Our study also revealed, for the first time, that the secondary metabolite cluster responsible for synthesis of the siderophore desferrioxamine is under the control of SCB signalling. Moreover, expression of the genes encoding enzymes for primary metabolism pathways, which supply antibiotic precursors and genes for morphological differentiation, was found shifted earlier in time in the mutant. In conclusion, our time series analysis demonstrates new details of the regulatory effects of the γ-butyrolactone system in Streptomyces.

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