6533b861fe1ef96bd12c592a

RESEARCH PRODUCT

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

Soohyun UmJanis FrickeThorsten HeinzelFelix SchalkBenjamin H. ConlonNils JägerTanja SchirmeisterChristine BeemelmannsHannah MausMichael Poulsen

subject

Antifungal0303 health sciencesProteasesProteasemedicine.drug_classGeneral Chemical Engineeringmedicine.medical_treatmentGeneral ChemistryBiologyGenomeChemistry03 medical and health sciences0302 clinical medicineMetabolomicsBiochemistrySymbiosis030220 oncology & carcinogenesisGene clustermedicineHistone deacetylase030304 developmental biology

description

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.

https://doi.org/10.1039/d1ra00997d