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Isolation, characterization, and bioactivity profiling of oxazoline containing madurastatin siderophores from Actinomadura sp.

The Journal of Antibiotics volume 75, pages 576–582 (2022)Cite this article

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Abstract

Nine new hydroxyphenyloxazolines, madurastatin B4, C2, D3 and D4, E1 and E2, F1 as well as G1 and G2 (8–16), along with two new enantiomers of madurastatin D1 (ent-6) and D2 (ent-7) and two known congeners, madurastatin B1 (2) and C1 (5), were isolated from the liquid culture of Actinomadura sp. ST100801 based on the initial activity against Escherichia coli screened in bicarbonate-supplemented Mueller Hinton II medium and identification via molecular networking. Structure elucidation was achieved by comprehensive 1D and 2D NMR as well as MS/MS fragmentation analyses. Their absolute configuration was determined by Marfey’s analysis. Complemented with functionalized hydroxyphenyloxazolines (2, 4, 17–18) obtained by total synthesis, the isolated compounds were evaluated for antibacterial activities revealing MICs down to 4 µg ml−1 against Moraxella catarrhalis. Therefore, this study enlarges the family of madurastatin siderophores.

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Acknowledgements

This study was financially supported by the Hessen State Ministry of Higher Education, Research, and the Arts (HMWK) via generous grant for the LOEWE Research Center Insect Biotechnology and Bioresources. Sanofi-Aventis Deutschland GmbH and Evotec International GmbH contributed in the framework of the Sanofi-Fraunhofer Natural Product Center of Excellence/Fraunhofer Evotec Natural Products Excellence Center. We thank Dr. Armin Bauer, Dr. Heike Hausmann, and Dr. Christoph Pöverlein for valuable discussions and the NMR department of the Justus-Liebig University Giessen for technical assistance. We gratefully acknowledge Christine Wehr for supporting the fermentation, Judith Härter for assisting the isolation, Kirsten Bommersheim for MIC determination, Christoph Hartwig for assistance regarding LCMS measurements, and Dr. Dennis Gerbig (Justus-Liebig University Giessen) for performing the UV/Vis measurements.

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Authors and Affiliations

  1. Branch for Bioresources, Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Ohlebergsweg 12, 35392, Giessen, Germany

    Mona-K. Bill, Yolanda Kleiner, Jana L. Flügel, Marius Spohn, Michael Marner, Sanja Mihajlovic, Andreas Vilcinskas, Till F. Schäberle & Maria A. Patras

  2. Institute of Organic Chemistry, Justus-Liebig University Giessen, Heinrich-Buff-Ring 17, 35392, Giessen, Germany

    Jana L. Flügel

  3. Sanofi-Aventis Deutschland GmbH, R&D Integrated Drug Discovery, Industriepark Höchst, 65926, Frankfurt am Main, Germany

    Michael Kurz & Peter E. Hammann

  4. Institute for Insect Biotechnology, Justus-Liebig University Giessen, Heinrich-Buff-Ring 26–32, 35392, Giessen, Germany

    Andreas Vilcinskas & Till F. Schäberle

  5. Evotec International GmbH, Marie-Curie-Straße 7, 37079, Göttingen, Germany

    Peter E. Hammann & Sören M. M. Schuler

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  1. Mona-K. Bill
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Correspondence to Maria A. Patras or Sören M. M. Schuler.

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MK, PEH, and SMMS are or have been employed by Sanofi-Aventis Deutschland GmbH and Evotec International GmbH, respectively.

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Bill, MK., Kleiner, Y., Flügel, J.L. et al. Isolation, characterization, and bioactivity profiling of oxazoline containing madurastatin siderophores from Actinomadura sp.. J Antibiot 75, 576–582 (2022). https://doi.org/10.1038/s41429-022-00557-z

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