IDENTIFICATION OF SMALL MOLECULES THAT REGULATE NEMATODE – ENVIRONMENT INTERACTIONS
Kariya, Maro J
One of the central channels of nematode-environment interactions is through small molecules (non-polymeric chemical entities with a molecular mass <1000 Daltons). Nematodes release an abundance of small molecules which affect their environment, such as the ascarosides, di-deoxy sugar lipids which control the development and behavior of nematodes and other members of their environment. Through the advancement of high-resolution mass spectrometry and analysis software, we now find a wealth of other small molecules produced by nematodes which play key roles in their environmental interactions. Herein the author describes the integrated use of 2D NMR and high-resolution UHPLC-MS/MS to aid metabolomics of complex natural samples to characterize small molecules that regulate interactions between nematodes and their environment. Combining these analytical techniques with biological assay data, the author has characterized small molecules from nematodes which elicit defensive responses in other nematodes and affect microbial and nematode growth. The library of small molecules presented in this dissertation provide a new layer of structural diversity in nematodes and define a path forward in discovering other molecules of their kind. The novel small molecules shown in this thesis include - Branched chain sulfolipids (sufal/ac), molecules that cause defensive behavior in prey nematodes that appear to be linked to the development of the predator nematode’s mouth dimorphism. Cyclic sulfates (cysul), a class of metabolites unprecedented in nature, with possible epoxide precursors that suggest a straightforward biosynthetic pathway. The cyclic sulfates, unlike the branched chain sulfolipids, do not affect defensive behaviors in other nematodes, but may play a yet undiscovered role in a nematode’s interactions with its environment. Cyclopropyl lipids (cpfa), nematode derivatives of bacteriogenic metabolites which inhibit microbial growth in several species. The activity of these lipids was found to be stereochemically specific, suggesting that the effect on microbial growth may be through a signaling mechanism. Through these studies the author hopes to convey connections between small molecules created by nematodes with their environment and draw parallels with their potential effect on other organisms.
173 pagesSupplemental file(s) description: Supplementary File 1.
Antibiotic; Avoidance; Cyclic; Predator; Sulfate; Sulfolipid
Baskin, Jeremy M.; Crane, Brian
Chemistry and Chemical Biology
Ph. D., Chemistry and Chemical Biology
Doctor of Philosophy
dissertation or thesis