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

  • Sebastian L. Wenski
  • Diana Kolbert
  • Gina L. C. Grammbitter
  • Helge B. BodeEmail author
Natural Products - Original Paper


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.


Xenorhabdus Fabclavine NRPS–PKS hybrid Antibiotic Natural product biosynthesis 



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.

Supplementary material

10295_2018_2124_MOESM1_ESM.docx (3 mb)
Supplementary material 1 (DOCX 3119 kb)


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Copyright information

© Society for Industrial Microbiology and Biotechnology 2019

Authors and Affiliations

  1. 1.Molekulare Biotechnologie, Fachbereich BiowissenschaftenGoethe Universität FrankfurtFrankfurtGermany
  2. 2.Buchmann Institute for Molecular Life Sciences (BMLS)Goethe Universität FrankfurtFrankfurtGermany

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