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

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.

Automated summary

Targeted metabolomic analysis of Pseudoxylaria sp. X187 identified two new lipopeptidic congeners, xylacremolides C and D, which showed weak histone deacetylase inhibitory and antifungal activities, as well as moderate protease inhibition activity against a panel of nine human, viral, and bacterial proteases. A putative xy gene cluster was identified from draft genome data generated by Illumina and PacBio sequencing, along with RNAseq studies.