Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Chemistry

Supervisor

Mark Sumarah

Affiliation

Agriculture and Agri-Food Canada

2nd Supervisor

Ken Yeung

Co-Supervisor

Abstract

This thesis focuses on the application of fungal natural product chemistry for the use of agriculture fungal pathogenesis research. The research in this work uses many analytical chemistry techniques and instruments such as HPLC, LC-MS/MS and NMR. In Chapter 2, a diagnostic fragmentation module was developed for the identification of compound classes in crude fungal extracts. This module identified the classes cytochalasins and chaetoglobosins from extracts of Penicillium, Chaetomium, and Xylaria. From these extracts a new chaetoglobosin was discovered and the module was implemented into the open-source software package MZmine 2.0. Chapter 3 discusses analytical chemistry techniques with the quantification of mycotoxin exposure in an at-risk population of Rwandan women through biofluid screening. The quantitated mycotoxins include deoxynivalenol, aflatoxin, zearalenone, fumonisin, and ochratoxin in addition to their derivatives. In total, 11 mycotoxins were quantified using isotopically labelled internal standards, with this chapter also overviewing their simplified synthesis. This study revealed the importance of mycotoxin screening and control in these at-risk populations. Chapters 4 – 6 of this thesis is focused on Ilyonectria mors-panacis and its pathogenicity as root rot on American ginseng. In Canada it is expected at time of harvest to lose about 20-30% of total crop yield to root rot with extreme cases experiencing severe loss of 80-100%. Ilyonectria root rot is also a major factor in the longer-term issue of replant disease, preventing subsequent plantings of ginseng in the same field for decades after initial planting. The work included in these chapters focuses on discovering new natural products from Ilyonectria mors-panacis and identifying virulence factors. Overall this pathogen produced a large number of resorcylic acid lactones, of which nine were isolated and identified, including a new natural product, Radicicol E. Additionally, an iron-chelating siderophore – N,N’,N”-Triacetylfusarinine C – was identified as a virulence factor and was pursued as a potential treatment method for root rot using enzymatic degradation. This treatment showed promising results for targeted treatment of ginseng root rot, however, application methods would need to be improved for practical use. Overall, this thesis explores a variety of disciplines which are required of a natural product chemist and demonstrates applications of natural product discovery.

Summary for Lay Audience

The origins of medical drugs such as Aspirin often have long histories of use, not as the pure drug that is used today, but as herbal remedies. The molecule responsible for the medicinal activity is known as a natural product; the people that study these molecules are natural product chemists. This thesis displays the variety among natural products and describes how natural product chemists study these molecules. It began by reviewing software that can be used by natural product chemists to quickly determine what molecules may be produced by an organism without needing to perform the complex steps required to obtain a purified compound. However, not all natural products are beneficial or act as drugs, many of these molecules can be harmful to human health. The work presented, focuses on assessing exposures to fungal toxins called mycotoxins in at-risk populations. Using a sample of women from Rwanda, 11 different toxins were detected, and it was found that many of these women were experiencing exposures above safe levels, suggesting that more regulation is required. The final chapters of this thesis cover plant diseases, specifically ginseng root rot. Ginseng is an important cash crop in Canada, which is the third largest producer of ginseng in the world. Root rot is a fungal disease which destroys the crop. It is expected for a farmer to lose between 20-30% of their crop at time of harvest and even more in severe cases. This thesis searches for natural product indicators of the disease and determines if there is a natural product factor in its severity. It was found that a group of molecules called resorcylic acid lactones play a major role in the disease and new member belonging to this group was discovered. Additionally, an iron-binding molecule was found to contribute to disease severity as well. This work went further to break down this iron binding molecule to control the disease and found promising results, leading to potential treatment methods which will be explored in the future.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Download

Share

COinS