Work Package 4: Isolation and Structure Analysis

The main target of this work package is to isolate and to elucidate the structures of compounds responsible for the biological activity of extracts and organisms pinpointed in WP1, WP2 and WP3. Besides this, one major aspect will be the identification of known natural products as early on as possible, ideally already at the level of the extract, to avoid the time-consuming and costly re-isolation of compounds previously described in the literature. This approach is commonly known as “dereplication”, and employs mainly mass spectrometric (MS) techniques.

For full structural characterisation of a new natural product, in most cases its isolation and purification to the level of a single pure compound is required. Isolation protocols generally use a suite of established chromatographic techniques (that need to be adopted on a case by case basis), but we will also make use of and further develop advanced methods such as “explorative solid phase extraction (E-SPE)”, the advantage of which is a reduction in the amount of solvents required.

The important process of dereplication (to avoid re-isolating already known compounds) currently is very labour intensive, and one of the topics in this work package will be to develop techniques for it to become more automated. To achieve this aim, software tools will be developed that process the output of various mass spectrometers (MS) and compare it to databases of known natural products (some commercially available, but some also specifically developed for this project), while at the same time involving advanced statistical data treatment (multivariate statistical techniques). One of the outcomes of this project will be an integrated database platform containing for instance information on the source organism, the chemical composition of its extract, bioassay data, and the chemical structures including experimental as well as predicted properties of its compounds.

Structure elucidation of new natural products heavily relies on nuclear magnetic resonance (NMR) spectroscopy, which is very powerful and provides a wealth of information, but on the other hand requires a substantial amount of training, experience and manpower, and thus very often can become a bottleneck in the biodiscovery process. For this reason, one of the objectives in this work package is to adopt and further develop computer-aided structure elucidation tools, and wherever possible, to integrate this information into the dereplication process.

WP leader: University of Aberdeen, Rainer Ebel