The Cryptic Genome, NMR Fingerprinting and Chemoinformatics Towards Anti-mycobacterial Discovery

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Quinn, Ronald

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Grkovic, Tanja

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2016
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Abstract

Secondary metabolites and their derivatives from microorganisms are a source of many important drugs. Indeed almost half of the antibiotics in the market are actinomycetes sourced natural products. However, advances in genome sequencing have revealed that actinomycetes are capable of producing still a far greater number of metabolites and potential drugs. The machinery for making the majority of secondary metabolites is silent when actinomycetes are grown under standard culture conditions. Chapters 2 and 3 of this thesis focused on two different approaches to de- silence bacterial cryptic genes. A method involving 1H NMR fingerprinting was used to compare and investigate the metabolic profile of bacteria. This method is more comprehensive than the traditional analytical techniques such as LC-PDA and LC- MS. Metabolite profiling by LC-PDA and LC-MS is dependent either on the existence of a chromophore (PDA detection) or the ability of a compound to be ionised (MS detection) and might not detect all of the changes of the secondary metabolome. However, all organic compounds containing a proton are easily detected by NMR. Naturally microbes are in contact with different organisms. They produce secondary metabolites to communicate within or between species and also to defend themselves. One strategy to de-silent the cryptic genes is to mimic the environment and co-culture the microbes.

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Thesis (PhD Doctorate)

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Doctor of Philosophy (PhD)

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School of Natural Sciences

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The author owns the copyright in this thesis, unless stated otherwise.

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Subject

Chemoinformatics

Anti-mycobacterial discovery

Cryptic genome

NMR fingerprinting

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