2. Academic Validation
  3. GNPS-guided discovery of xylacremolide C and D, evaluation of their putative biosynthetic origin and bioactivity studies of xylacremolide A and B

GNPS-guided discovery of xylacremolide C and D, evaluation of their putative biosynthetic origin and bioactivity studies of xylacremolide A and B

  • RSC Adv. 2021 May 24;11(31):18748-18756. doi: 10.1039/d1ra00997d.
Felix Schalk 1,  Janis Fricke 1,  Soohyun Um 1,  Benjamin H Conlon 2,  Hannah Maus 3,  Nils Jäger 4,  Thorsten Heinzel 4,  Tanja Schirmeister 3,  Michael Poulsen 2,  Christine Beemelmanns 1
Affiliations

Affiliations

  • 1 Chemical Biology of Microbe-Host Interactions, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute (HKI) Beutenbergstraße 11a 07745 Jena Germany Christine.beemelmanns@hki-jena.de.
  • 2 Section for Ecology and Evolution, Department of Biology, University of Copenhagen Universitetsparken 15 2100 Copenhagen East Denmark.
  • 3 Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University Mainz Staudingerweg 5 55128 Mainz Germany.
  • 4 Institute of Biochemistry and Biophysics at Center for Molecular Biomedicine (CMB), Department of Biochemistry, Friedrich Schiller University Jena Hans-Knöll-Straße 2 07745 Jena Germany.
PMID: 34046176 DOI: 10.1039/d1ra00997d
Abstract

Targeted HRMS2-GNPS-based metabolomic analysis of Pseudoxylaria sp. X187, a Fungal antagonist of the fungus-growing termite symbiosis, resulted in the identification of two lipopeptidic congeners of xylacremolides, named xylacremolide C and D, which are built from d-phenylalanine, l-proline and an acetyl-CoA starter unit elongated by four malonyl-CoA derived ketide units. The putative xya gene cluster was identified from a draft genome generated by Illumina and PacBio Sequencing and RNAseq studies. Biological activities of xylacremolide A and B were evaluated and revealed weak histone deacetylase inhibitory (HDACi) and Antifungal activities, as well as moderate Protease inhibition activity across a panel of nine human, viral and Bacterial proteases.

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