WP4 focuses on compound characterization and compound modification. Known compounds will be dereplicated (MS-MS networking, metabolomics, in silico dereplication based on biosynthetic genes), compounds isolated, and the chemical structures of novel compounds elucidated.

  • Fractionation of extracts using chromatographic methods and dereplication using LC-MS/MS and chemoinformatic tools.

  • Prioritisation of extracts based on chemical dereplication (WP4), bioassay data (WP5) and genome mining (WP2).

  • Isolation of pure compounds from prioritised extracts (WP5) using chromatographic methods followed by structural characterisation using spectroscopic methods. Compounds delivered to WP5 for screening and prioritisation.

  • Larger amounts of prioritised compounds isolated from extracts provided by WP5 for proof of concept and validation studies (mechanism of action, ADMET etc).

  • Generation of analogues of active compounds identified using biosynthetic engineering of pathways and chemoenzymatic synthesis.

  • Developing a pipeline to connect biosynthetic gene clusters through predicted structures to mass spectrometric fragmentation networks to speed up future dereplication.

  • Developing protocols compatible with extracts and natural products to maintain such libraries in the longer term for future screening efforts.