Work Package 4
Small Molecules-Generation of Chemical Diversity
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.