Date of Award
Winter 3-22-2025
Document Type
Dissertation
Degree Name
Ph.D.
Organizational Unit
College of Natural Science and Mathematics, Chemistry and Biochemistry
First Advisor
Allegra T. Aron
Second Advisor
Todd Wells
Third Advisor
Scott Horowitz
Fourth Advisor
Schuyler Van Engelenburg
Copyright Statement / License for Reuse
All Rights Reserved.
Keywords
Iron, Biosynthesis, Secondary metabolites, Mass spectrometry
Abstract
Iron is an essential element for nearly all living organisms, playing a central role in a wide range of biochemical processes. It is crucial for DNA synthesis, immune defense, oxygen transport, energy metabolism, and mitochondrial respiration. As a critical component of enzymes and proteins, iron facilitates its diverse functions through electron exchange, underscoring its indispensable role in sustaining life and promoting overall health at the molecular level. The role of iron in the biosynthesis of secondary metabolites forms the central focus of my PhD thesis. To investigate this broad research area, I conducted three distinct projects, each exploring a specific aspect of iron’s role in bacterial natural products. Throughout my research, I utilized mass spectrometry as the primary tool to address these diverse topics. In the first project, I investigated radical Sadenosylmethionine (rSAM) enzymes, which require iron-sulfur (Fe-S) clusters for activity. I discovered and characterized a novel class of rSAM enzymes, termed cyclopropyl synthases, that catalyze unprecedented chemical transformations on peptide substrates. In the second project, I combined advanced mass spectrometry techniques with extensive statistical analysis and novel computational tools to identify a previously unknown metal-binding molecule. Produced by the well-studied uropathogen Proteus mirabilis, this molecule significantly enhances bacterial fitness. Finally, in the third project, I examined metabolic changes in fecal samples from mice subjected to differential iron diets over a 14-week period. These findings underscore the critical role of iron not only in bacterial biochemical processes but also in host physiology, providing insights into diseases associated with nutrient availability.
Overall, my research highlights the versatility of iron in supporting a multitude of biological functions essential for health and viability. Furthermore, this work demonstrates that integrating mass spectrometry with cutting-edge computational approaches offers a robust and adaptable framework for studying natural products, even in the absence of prior knowledge of their identities.
Copyright Date
3-2025
Publication Statement
Copyright is held by the author. User is responsible for all copyright compliance.
Rights Holder
Anastasiia Kostenko
Provenance
Received from author
File Format
application/pdf
Language
English (eng)
Extent
223 pgs
File Size
19.3 MB
Recommended Citation
Kostenko, Anastasiia, "Exploring Microbial Utilization of Iron via Mass Spectrometry" (2025). Electronic Theses and Dissertations. 2522.
https://digitalcommons.du.edu/etd/2522