DEREPLICATION


The demands of high throughput bioassays place emphasis not only on the search for biological activity, but also on the recognition and elimination of known active metabolites, potential artefacts and non-specific actives early in the discovery process. With over 25,000 microbial natural products now known, the ability to quickly recognise and dereplicate known actives is the key to ensuring that the focus is always on novel chemistry. While many laboratories recognise the need, few can provide more than a rudimentary dereplication service.

Microbial Screening has developed COMET, a metabolite recognition software that compiles and analyses co-metabolite patterns in natural product mixtures. The metabolite patterns of an organism are not random. For virtually all macro- and microorganisms the types of metabolites produced are highly diagnostic for any given species. Our approach is different from those driving other recognition software, because we consider an active as part of the co-metabolite pattern in which it occurs.

COMET takes the data generated by DAD-HPLC and creates compact databases of the chromatograms and UV spectra. These databases can then be interrogated with flexible analytical tools, which enable rapid understanding of complex natural product extracts. With over 1,000,000 UV spectra COMET represents the state of the art in rapid metabolite analysis.

With COMET we can recognise novelty in co-metabolite patterns and eliminate known metabolites producers and replicates early.


A screen shot of COMET in Browse mode demonstrates the co-metabolite pattern of MST MF2825, the number of peaks, production level and the UV spectra of each of the peaks in detail.
While COMET provides the technology for dereplication, it is the standards (reference compounds) that provide the power and quality of the approach. Microbial Screening's Chemical Library has been constructed to provide a broad view of natural products, together with a range of specific and non-specific chemicals relevant to drug discovery. More importantly, our Type Species Library is drawn from most genera of microorganisms. Extracts from the Type Species Library provide the in situ metabolite patterns for virtually all important microbial metabolite classes.

Chemical Library - over 5,000 compounds
  • Known micro- and macro-organism metabolite standards
  • Pharmacological standards that act on a range of receptor and enzyme targets
  • Endogenous metabolites such as fatty acids, amino acids and carbohydrates
  • Interfering materials like polyamines, polyacids, tannins, low molecular amines and acids that are often responsible for high false positives in some screens
  • Unusual chromophores
Type Species Library - over 5,000 species
  • >2,500 fungi encompassing species from over 250 genera
  • >2,500 actinobacteria including species from 100 genera comprising this class
  • >1,000 bacteria derived from a broad cross section of terrestrial and marine environments

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