Date

June 2010

Document Type

Thesis

Degree Name

M.S.

Department

Dept. of Science & Engineering

Institution

Oregon Health & Science University

Abstract

Natural products are the most valuable source for the discovery and development of new drugs, and have played a pivotal role throughout the history of medicine. The emergence of new diseases and evolution of pathogens has created a dire need for the discovery of new drug classes. Teredinibacter turnerae strain T7901, a bacterial symbiont of shipworms, devotes a significant proportion of its genome to the biosynthesis of complex secondary metabolites, and holds the promise of finding novel bioactive metabolites within its genetic potential. These secondary metabolites could function as a chemical defense mechanism in the context of the symbiosis, and their biological activities are likely to be of pharmaceutical relevance as well. This symbiont also has an important nutritional role, by providing its host with the enzymes that facilitate complex polysaccharide degradation. These enzymes are highly tuned to specifically degrade the primary constituents of woody plant cell walls, and are of interest for the development of biofuel applications. The present study used microarray and quantitative reverse transcription PCR expression analyses to characterize regulation systems of the secondary metabolite and carbohydrate-active genes in the T. turnerae genome. Bioassays were used to characterize the properties of some of the antimicrobial secondary metabolites, as well as the organisms that show susceptibility to them. Collectively, these analyses show that the biosynthesis of an antibacterial molecule and catecholate-like siderophore are regulated by phosphate and iron availability, respectively, and provide evidence for which gene clusters are responsible for their biosyntheses. Outer membrane protein analysis provides additional evidence of the proteins responsible for ferric-siderophore uptake in T. turnerae. Microarray expression analysis of the bohydrate-active genes shows that many are highly expressed, even in the absence of substrate. The results from this study support the notion that the symbiont plays a crucial nutritional role in the symbiosis, and suggest a novel role in chemical defense against competing microbes. Furthermore, this study has optimized conditions for production of secondary metabolites and cellulolytic enzymes to facilitate future discovery and development of biotechnological applications.

Identifier

doi:10.6083/M4K35RM6

Division

Div. of Environmental & Biomolecular Systems

School

School of Medicine

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