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

  • Dumitrita Iftime
  • Andreas Kulik
  • Thomas Härtner
  • Sabrina Rohrer
  • Timo Horst Johannes Niedermeyer
  • Evi Stegmann
  • Tilmann Weber
  • Wolfgang Wohlleben
Natural Products

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.

Keywords

Genome mining Streptomyces Natural products Secondary metabolites Isorenieratene Deoxydehydrochorismic acid 

Notes

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.

Supplementary material

10295_2015_1685_MOESM1_ESM.docx (2.7 mb)
Supplementary material 1 (DOCX 2801 kb)

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Copyright information

© Society for Industrial Microbiology and Biotechnology 2015

Authors and Affiliations

  • Dumitrita Iftime
    • 1
    • 2
  • Andreas Kulik
    • 1
  • Thomas Härtner
    • 1
  • Sabrina Rohrer
    • 1
  • Timo Horst Johannes Niedermeyer
    • 1
    • 2
  • Evi Stegmann
    • 1
    • 2
  • Tilmann Weber
    • 1
    • 2
    • 3
  • Wolfgang Wohlleben
    • 1
    • 2
  1. 1.Lehrstuhl für Mikrobiologie/Biotechnologie, Interfakultäres Institut für Mikrobiologie und Infektionsmedizin TübingenEberhard Karls Universität TübingenTübingenGermany
  2. 2.German Centre for Infection Research (DZIF)Partner Site TübingenTübingenGermany
  3. 3.The Novo Nordisk Foundation Center for BiosustainabilityTechnical University of DenmarkHørsholmDenmark

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