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.

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

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

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    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.

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

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

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

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