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Title: Deciphering the Small Molecule Language of Algal-Bacterial Symbioses
Authors: Wang, Rurun
Advisors: Seyedsayamdost, Mohammad
Contributors: Chemistry Department
Keywords: biosynthesis
interspecies interaction
natural product
tropodithietic acid
Subjects: Chemistry
Issue Date: 2017
Publisher: Princeton, NJ : Princeton University
Abstract: Bacterial secondary metabolites provide a major source of therapeutic molecules and play critical roles in microbial symbioses. Deciphering the small molecule language that underlies such symbiotic associations not only leads to discovery of new natural products, but also furthers our understanding of the principles that govern interspecies interactions. In a biogeochemically significant symbiosis between the Roseobacter species Phaeobacter inhibens and the microalga Emiliania huxleyi, a biphasic interaction model has been proposed. Each phase of the symbiosis is characterized by a set of molecules: beneficial metabolites are exchanged in the mutualistic phase, including the broad-spectrum antibiotic tropodithietic acid (TDA), which protects the algal-bacterial microassembly. The interaction switches to the alternative parasitic phase, possibly triggered by algal senescence. Under these conditions, the algae release lignin breakdown products, such as the p-coumaric acid (pCA), which induce bacterial production of a family of potent algaecides, the roseobacticides, to kill the algae. Herein we investigate the molecular mechanisms that potentiate each phase of the interaction. We first examine the mode of action of the antibiotic TDA. Using bacterial cytological profiling, primary metabolite analysis, and gene deletion studies, we find that TDA dissipates the proton motive force via an electroneutral proton-antiport mechanism and propose a new role for glutathione in providing immunity to TDA. Next, we investigate the biosynthesis and regulation of roseobacticides by P. inhibens and find a unique case of metabolite economy, where molecules from the two symbionts are pieced together to generate the algaecides. Roseobacticides and TDA are largely produced from the same biosynthetic pathway; the implications for this unusual phenomenon are discussed. We also expand the small molecule vocabulary of the algal-bacterial symbiosis by describing a new family of cryptic secondary metabolites, the roseochelins, produced in the parasitic phase of the association. One variant, roseochelin B, chelates iron and kills E. huxleyi with moderate potency. Lastly, we employ whole-cell transcriptomics to investigate the effects of algal pCA on P. inhibens. These studies further expand the small molecule repertoire of this interaction by revealing the cryptic siderophore, roseobactin, which is produced in response to pCA. A comprehensive model for roseobacter-microalgal symbioses is proposed.
Alternate format: The Mudd Manuscript Library retains one bound copy of each dissertation. Search for these copies in the library's main catalog:
Type of Material: Academic dissertations (Ph.D.)
Language: en
Appears in Collections:Chemistry

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