Characterization of structures and biosyntheses of ecologically important secondary metabolites in Escherichia coli and Xenorhabdus species

Gut microbes both compete for shared resources among neighboring species as well as promote synergistic interactions with the host in order to thrive in their extraordinarily complex environment. Bacterial secondary metabolites mediate these different types of interactions between the producer and its environment. Small molecule therapeutics, such as antibiotics, can elicit production of different secondary metabolites and may contribute to a dysregulated microbiota. In identifying novel bacterial-derived metabolites, we aim to understand the molecular mechanisms by which bacteria interact with the environment, which may serve as future biomarkers or therapeutics for microbiome-targeted intervention. To this end, my work is concerned with three key questions: first, what are the molecules that are important within an ecological niche; second, what interactions do they mediate; and third, how are these molecules biosynthesized. The work within this thesis addresses the above questions in two types of Enterobacteriaceae bacteria, Escherichia coli and the genus Xenorhabdus, combining metabolomics, genetics, and synthetic biology in order to better understand the chemical biology within the gut