Date of Award

Spring 2023

Document Type

Open Access Dissertation

Department

Chemistry and Biochemistry

First Advisor

Jei Li

Abstract

Bacterially derived secondary metabolites have repeatedly proved to be a valuable source of unique and biologically active compounds with applications far exceeding their well-known success as antimicrobials. The study of these molecules has led to a deeper understanding of the role of bacteria in the human body and how bacteria influence the development and progression of specific diseases. This dissertation covers two research projects that each detail investigations into the bioactivity of specific bacterial metabolites. In Chapter 2, bacteria isolated from pseudomyxoma peritonei (PMP) cancer tissues are studied to ascertain their effect on PMP cancer cells. This research led to the discovery of a species of Streptomyces designated PMP498-3 that is capable of invading PMP cancer cells. Additionally, analysis of its bacterial extracts identified a unique cyclic lipopeptide metabolite named myxomapeptin that was later found to be biologically active, with effects on PMP cell viability and energy metabolism. Interestingly, myxomapeptins showed a high degree of selectivity for PMP cancer cells, as their associated bioactivity was not reproducible in the non-PMP cell lines tested.

In Chapter 3, the bioactivity of two unusual small molecule metabolites called sulfonolipids were investigated. Findings indicate that these sulfonolipids are capable of manipulating inflammation response through interactions with the TLR4/MD-2 receptor complex, and can prevent the pro-inflammatory M1 polarization of macrophagic immune cells. The work presented here establishes clear evidence for a complex and nuanced relationship between bacterial secondary metabolites and disease.

Rights

© 2023, Zachary Evanoff Ferris

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