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Identification and activation of novel biosynthetic gene clusters by genome mining in the kirromycin producer Streptomyces collinus Tü 365

  • Natural Products
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Streptomycetes are prolific sources of novel biologically active secondary metabolites with pharmaceutical potential. S. collinus Tü 365 is a Streptomyces strain, isolated 1972 from Kouroussa (Guinea). It is best known as producer of the antibiotic kirromycin, an inhibitor of the protein biosynthesis interacting with elongation factor EF-Tu. Genome Mining revealed 32 gene clusters encoding the biosynthesis of diverse secondary metabolites in the genome of Streptomyces collinus Tü 365, indicating an enormous biosynthetic potential of this strain. The structural diversity of secondary metabolisms predicted for S. collinus Tü 365 includes PKS, NRPS, PKS-NRPS hybrids, a lanthipeptide, terpenes and siderophores. While some of these gene clusters were found to contain genes related to known secondary metabolites, which also could be detected in HPLC–MS analyses, most of the uncharacterized gene clusters are not expressed under standard laboratory conditions. With this study we aimed to characterize the genome information of S. collinus Tü 365 to make use of gene clusters, which previously have not been described for this strain. We were able to connect the gene clusters of a lanthipeptide, a carotenoid, five terpenoid compounds, an ectoine, a siderophore and a spore pigment-associated gene cluster to their respective biosynthesis products.

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Acknowledgments

This work was supported by ERA-IB-GenoDrug (BMBF FKZ 0315930), The German Center for Infection Research (DZIF) (TTU 09.802) and the Graduate College 1708 (Bacterial Survival Strategies). T. Weber is supported by a grant from the Novo Nordisk Foundation. The authors acknowledge P. Schmieder (FMP Berlin-Buch) for recording the NMR spectra for deoxydehydrochorismic acid.

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  1. Lehrstuhl für Mikrobiologie/Biotechnologie, Interfakultäres Institut für Mikrobiologie und Infektionsmedizin Tübingen, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 28, 72076, Tübingen, Germany

    Dumitrita Iftime, Andreas Kulik, Thomas Härtner, Sabrina Rohrer, Timo Horst Johannes Niedermeyer, Evi Stegmann, Tilmann Weber & Wolfgang Wohlleben

  2. German Centre for Infection Research (DZIF), Partner Site Tübingen, 72076, Tübingen, Germany

    Dumitrita Iftime, Timo Horst Johannes Niedermeyer, Evi Stegmann, Tilmann Weber & Wolfgang Wohlleben

  3. The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle Alle 6, 2970, Hørsholm, Denmark

    Tilmann Weber

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  1. Dumitrita Iftime
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Special Issue: Natural Product Discovery and Development in the Genomic Era. Dedicated to Professor Satoshi Ōmura for his numerous contributions to the field of natural products.

We would like to dedicate this publication to Alfred Pühler on the occasion of his 75th birthday.

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Iftime, D., Kulik, A., Härtner, T. et al. Identification and activation of novel biosynthetic gene clusters by genome mining in the kirromycin producer Streptomyces collinus Tü 365. J Ind Microbiol Biotechnol 43, 277–291 (2016). https://doi.org/10.1007/s10295-015-1685-7

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