Date of Award
1-1-2024
Document Type
Thesis
Degree Name
M.S. in Pharmaceutical Science
First Advisor
Cole Stevens
Second Advisor
Paul Boudreau
Third Advisor
Marc Slattery
Relational Format
dissertation/thesis
Abstract
Myxobacteria are distinguished by their ability to produce a spectrum of natural products,positioning them as an active resource for therapeutic discovery. These products include metabolites with significant antibacterial, antifungal, cytotoxic, antiviral, and immunosuppressive properties. Current synthetic biology tools for the exploration of myxobacteria are not as advanced as those for the well-studied Streptomyces. This thesis presents an evolution of synthetic biology techniques specifically designed for the exploitation of myxobacteria in the realm of natural product discovery. Chapter One investigates the potential of myxobacteria to act as heterologous hosts due to their large genomes and their capacity for diverse biosynthetic processes. The chapter delves into the examination of horizontally acquired biosynthetic gene clusters (BGCs), notably the indigoidine BGC from Melittangium primigenium, which is postulated to be derived from Streptomyces. This chapter is divided into two pivotal phases: the first validates the functionality of such horizontally acquired BGCs and understanding their genetic evolution post-acquisition. The subsequent phase introduces an innovative visual reporter platform engineered from the myxobacterial indigoidine BGC, facilitating the effective visual screening of myxobacteria for hosting BGCs. Chapter Two schemes into the unexplored genetic territories of environmental myxobacterial isolates. It spotlights a natural plasmid within Cystobacter ferrugineus that harbors a BGC responsible for producing the metabolite tubulysin, signifying the first instance of a myxobacterial plasmid intrinsically expressing a therapeutically significant metabolite without genetic manipulation. This discovery offers a robust framework for utilizing natural plasmids in drug development. By broadening the synthetic biology toolkit for myxobacteria, this thesis promises to unlock the potential of myxobacteria as a source of novel bioactive compounds.
Recommended Citation
Shehata, Nawal Mohamed Hamed Elsayed, "Heterologous Expression, Isolation, and Metabolomic Profiling of Myxobacteria to Explore Their Potential in Natural Product Biosynthesis" (2024). Electronic Theses and Dissertations. 2874.
https://egrove.olemiss.edu/etd/2874