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

Felix Schalk; Janis Fricke; Soohyun Um; Benjamin H. Conlon; Hannah Maus; Nils Jäger; Thorsten Heinzel; Tanja Schirmeister; Michael Poulsen; Christine Beemelmanns

doi:10.1039/D1RA00997D

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

Felix Schalk,‡^a Janis Fricke,

‡^a Soohyun Um,^a Benjamin H. Conlon,

^b Hannah Maus,

^c Nils Jäger,^d Thorsten Heinzel,^d Tanja Schirmeister,

^c Michael Poulsen

^b and Christine Beemelmanns*^a

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* Corresponding authors

^a Chemical Biology of Microbe-Host Interactions, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute (HKI), Beutenbergstraße 11a, 07745 Jena, Germany
E-mail: Christine.beemelmanns@hki-jena.de

^b Section for Ecology and Evolution, Department of Biology, University of Copenhagen, Universitetsparken 15, 2100 Copenhagen East, Denmark

^c Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University Mainz, Staudingerweg 5, 55128 Mainz, Germany

^d 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

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.

This article is part of the themed collection: Emerging Investigators Series

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

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

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