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Fabclavine biosynthesis in X. szentirmaii: shortened derivatives and characterization of the thioester reductase FclG and the condensation domain-like protein FclL

  • Natural Products - Original Paper
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Journal of Industrial Microbiology & Biotechnology

Abstract

Fabclavines, unusual peptide–polyketide–polyamine hybrids, show broad-spectrum bioactivity against a variety of different organism like Gram-positive and -negative bacteria, fungi and protozoa. We elucidated the biosynthesis of these NRPS–PKS hybrids in Xenorhabdus szentirmaii by deletion of most genes encoded in the fabclavine BGC and subsequent analysis of produced fabclavine or polyamine intermediates. Thereby, we identified shortened fabclavines similar to the bioactive zeamines. Furthermore, we analyzed the thioester reductase FclG and the free-standing condensation domain-like protein FclL in detail and observed low substrate specificity for both enzymes.

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Acknowledgements

This work was supported by the DFG and the LOEWE Schwerpunkt MegaSyn supported by the State of Hessen. H.B.B. acknowledges the Deutsche Forschungsgemeinschaft for funding of the Impact II qTof mass spectrometer (INST 161/810-1). Furthermore, we would like to thank Dr. Hendrik Wolff and Peter Grün for technical assistance with the GC–MS measurements and Prof. Dr. Michael Karas for support with the MALDI-MS measurements.

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Authors and Affiliations

  1. Molekulare Biotechnologie, Fachbereich Biowissenschaften, Goethe Universität Frankfurt, 60438, Frankfurt, Germany

    Sebastian L. Wenski, Diana Kolbert, Gina L. C. Grammbitter & Helge B. Bode

  2. Buchmann Institute for Molecular Life Sciences (BMLS), Goethe Universität Frankfurt, 60438, Frankfurt, Germany

    Helge B. Bode

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  1. Sebastian L. Wenski
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  2. Diana Kolbert
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  3. Gina L. C. Grammbitter
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  4. Helge B. Bode
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Correspondence to Helge B. Bode.

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This article is part of the Special Issue “Natural Product Discovery and Development in the Genomic Era 2019”.

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Wenski, S.L., Kolbert, D., Grammbitter, G.L.C. et al. Fabclavine biosynthesis in X. szentirmaii: shortened derivatives and characterization of the thioester reductase FclG and the condensation domain-like protein FclL. J Ind Microbiol Biotechnol 46, 565–572 (2019). https://doi.org/10.1007/s10295-018-02124-8

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  • DOI: https://doi.org/10.1007/s10295-018-02124-8

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