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Title page for ETD etd-08152018-020250


Type of Document Dissertation
Author Covington, Brett Casey
Author's Email Address bcovington15@gmail.com
URN etd-08152018-020250
Title Expediting Natural Product Discovery with Mass-Spectrometry based Metabolomic Analyses
Degree PhD
Department Chemistry
Advisory Committee
Advisor Name Title
Brian O. Bachmann Committee Chair
David W. Wright Committee Member
Eric P. Skaar Committee Member
John A. McLean Committee Member
Keywords
  • secondary metabolites
  • mass spectrometry
  • metabolomics
  • Natural products
  • actinomycetes
Date of Defense 2018-07-20
Availability unrestricted
Abstract
Natural products remain valuable sources for modern drug discovery, yet natural product discovery is hindered by poor production in lab cultivated organisms and/or poor observability from complex microbial extracts. We hypothesized that producing organisms use their natural products to respond to environmental cues from competing organisms, to nutrients and other physical factors, and when grown in isolation in the lab the organisms no longer receive these cues and subsequently do not produce their compounds of interest. Herein we describe the applications of environmental stimuli to boost natural product production in cave-derived actinomycetes in combination with comparative metabolomics analyses to prioritize natural products from whole culture extracts. In addition to prioritization with principal component analyses, we demonstrate for the first time the utility of self-organizing map analytics to prioritize natural products from large numbers of stimuli conditions within a single analysis. Many of the metabolites prioritized by comparative metabolomics were isolated and identified as natural products some of which, the ciromicins and funisamine, were identified as entirely novel natural products.
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