Dereplication of the Actinomycete Metabolome as a Source of Bioactive Secondary Metabolites
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Natural products (NPs) and their derivatives have historically played a vital role in drug discovery by serving as an invaluable source of therapeutic agents and potential drug leads. Among the established sources of NPs, microorganisms have proven to be promising candidates for the production of novel scaffolds as well as marketable drugs. They have yielded some of the most economically relevant leads for the pharmaceutical industry, including penicillin G, cephalosporin C, tetracycline, mevastatin and rapamycin. At present, approximately 32,000-34,000 bioactive microbial metabolites have been isolated and even though it has been estimated that this amount represent less than 10% of the total number of small molecules that these microorganisms can biosynthesise. Declining in productivity and discovery of novel molecules over the past two decades has been one the reasons because large pharmaceutical companies have closed their microbial drug discovery programs. New approaches have been developed to address the problem of rediscovery of microbial natural products. One of these strategies involves the isolation, characterisation and screening of novel/rare actinomycete taxa sourced from unique and underexplored environments. Hence, this investigations aims to access to the unique components of the drug-like natural product metabolome of termite gut-associated actinomycetes using a new NMR-based methodology. This approach was used to accelerate the identification of all the constituents with unique spectral patterns comprising the lead-like enhanced fractions.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Natural Sciences
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Bioactive secondary metabolites