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http://hdl.handle.net/11375/19015
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DC Field | Value | Language |
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dc.contributor.advisor | Nathan, Magarvey | - |
dc.contributor.author | Johnston, Chad William | - |
dc.date.accessioned | 2016-04-01T20:23:54Z | - |
dc.date.available | 2016-04-01T20:23:54Z | - |
dc.date.issued | 2016 | - |
dc.identifier.uri | http://hdl.handle.net/11375/19015 | - |
dc.description.abstract | Microbial natural products have been one of the most important sources of drugs for the last century. However, as increasing numbers of natural products were discovered, researchers increasingly found previously described compounds, leading to a decline in efficiency and perceived future prospects for natural products discovery. Now, we know from genome sequencing that massive numbers of natural products remain to be discovered, indicating that new strategies and techniques may be required to leverage new bio- and chemo-informatic data to reveal these previously undiscovered small molecules. First, I developed an automated database search strategy that could reveal natural products in liquid chromatography coupled mass spectrometry (LCMS) data based on the in silico fragmentation of automated structure predictions based on genome sequence inputs. This Genomes-to-Natural Products pipeline (GNP) was used as an automated approach for uncovering new modular microbial natural products, identifying structures from cryptic biosynthetic gene clusters as well as from organisms which had not been known to produce natural products previously. Next, I generated a comprehensive library of microbial antibacterial natural products and used a retrobiosynthetic algorithm to identify chemical families with conserved mechanisms of action. This approach led to investigations of the telomycin family of antibiotics, revealing that this old molecule has a novel target. Finally, I led two targeted investigations of organisms that had been identified as potential natural product producers via bioinformatic analysis, revealing new chemical compounds from Legionella and Delftia. Throughout this thesis, bio- and chemo-informatics have been used to illustrate new approaches to natural products research, generating novel platform technologies and investigating untouched organisms as a means of rediscovering the potential of microbial natural products. | en_US |
dc.language.iso | en | en_US |
dc.title | New Techniques Facilitate the Discovery and Study of Modular Microbial Natural Products | en_US |
dc.type | Thesis | en_US |
dc.contributor.department | Biochemistry and Biomedical Sciences | en_US |
dc.description.degreetype | Thesis | en_US |
dc.description.degree | Doctor of Philosophy (PhD) | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Johnston_Chad_W_201603_PhD.pdf | Thesis manuscript | 12.9 MB | Adobe PDF | View/Open |
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