Dissertation
Exploration of natural sources in search of novel bioactive molecules
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Autumn 2021
DOI: 10.17077/etd.006301
Abstract
In recent years the number of fungal infections caused by Candida, Cryptococcus, and Aspergillus species has increased. Groups of immunocompromised individuals comprise the populations most at risk from these fungal infections. In order to fight these pathogens, new treatments are needed, as current methods are not adequately effective due to drug resistance and toxicity. Fungi have proven to be excellent sources of bioactive secondary metabolites, including antifungal compounds. Our group’s approach to selecting fungal species for chemical investigation is based on targeting of specific ecological niche groups. The fungal cultures investigated in this thesis belong to two such groups: mycoparasitic/fungicolous and coprophilous fungi. Mycoparasitic and fungicolous fungi are species that colonize other fungi and sometimes cause damage to the host. This damage, when it occurs, is often caused by antifungal secondary metabolites. Investigation of 10 isolates of such fungi described in this thesis produced five known compounds and six new compounds. Although the culture extracts from which they were isolated showed antifungal activity, only one of the known compounds displayed antifungal properties.
Coprophilous fungi are species that grow on herbivore dung -- a nutrient-rich environment inhabited by many competing microorganisms. In order to succeed in this environment, some fungi may produce metabolites that inhibit competitors. Twenty-nine coprophilous fungal isolates were analyzed, ultimately yielding one new compound and 17 known compounds. Ten of these compounds display antifungal activity.
Although soil samples are not typically investigated by our group, there are a few investigations of cultures collected from soil samples reported in this thesis. Two cultures produced only known chemistry while four strains of Penicillium arenicola produced two new compounds. One of the known compounds displays antifungal activity while the other displays herbicidal activity. One of the new compounds displayed cytotoxicity against three human cancer cell lines.
Along with the fungal metabolite studies reported in this thesis, investigation of a new stilbenoid phytoalexin obtained from Aspergillus spp.-challenged peanut plants (Arachis hypogaea) is also described. This stilbenoid proved to be an interesting challenge due to its instability. Studies into these phytoalexins could provide a better understanding of how to combat Aspergillus species of fungi and the aflatoxins that they produce in agriculture and stored product settings.
The natural products encountered in this work belong to a range of compound classes, including terpenoids, meroterpenoids, polyketides, and peptides. Several different separation techniques were used to purify these compounds. Structure elucidation of these metabolites primarily employed various 1D and 2D NMR experiments in conjunction with mass spectrometry. Stereochemical features were assigned by analysis of coupling constants, NOE correlations, and/or ECD spectroscopy.
Details
- Title: Subtitle
- Exploration of natural sources in search of novel bioactive molecules
- Creators
- Cody Edward Earp
- Contributors
- James B Gloer (Advisor)Ned B Bowden (Committee Member)Edward G Gillan (Committee Member)Elizabeth A Stone (Committee Member)David F Wiemer (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Chemistry
- Date degree season
- Autumn 2021
- DOI
- 10.17077/etd.006301
- Publisher
- University of Iowa
- Number of pages
- xxviii, 238 pages
- Copyright
- Copyright 2021 Cody Edward Earp
- Language
- English
- Description illustrations
- illustrations (some color)
- Description bibliographic
- Includes bibliographical references (pages 228-238).
- Public Abstract (ETD)
Over the years, fungal infections have become more widespread. These infections are particularly dangerous to those with compromised immune systems. Since current methods of fighting fungal pathogens are not very effective due to growing resistance and toxicity of available drugs, new methods are needed. Fungi are prolific producers of bioactive metabolites, including antifungal compounds. Laboratory investigations of fungi described in this thesis were conducted by targeting ecological niche groups that are hypothesized to be productive sources of antifungal metabolites, such as mycoparasitic/fungicolous and coprophilous fungi. Mycoparasitic and fungicolous fungi colonize other fungi sometimes causing damage to the host, while coprophilous fungi colonize herbivore dung and have many fungal competitors. Along with the fungal natural products encountered in these studies, a natural product produced from Arachis hypogaea (the peanut plant) is also described. The peanut plant produced this natural product after it was challenged by an Aspergillus spp. This method of challenging the peanut plant may produce compounds that are effective at fighting fungi in agricultural settings.
The compounds described in this thesis were isolated by various separation techniques and characterized by mass spectrometry and a variety of NMR experiments. Many of these compounds display some level of bioactivity. The work conducted shows that fungi are good sources of natural products that have antifungal activity and other types of effects that could be useful in combating pathogenic organisms.
- Academic Unit
- Chemistry
- Record Identifier
- 9984210944102771
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