Graduation Year

2015

Document Type

Dissertation

Degree

Ph.D.

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Chemistry

Degree Granting Department

Chemistry

Major Professor

Bill J. Baker, Ph.D.

Co-Major Professor

Edward Turos, Ph.D.

Committee Member

Edward Turos, Ph.D.

Committee Member

James W. Leahy, Ph.D.

Committee Member

Dennis E. Kyle, Ph.D.

Keywords

Antarctica, co-culture, ecology, fungus, sponge

Abstract

Natural products continue to be a valuable source of compounds in research involving chemical ecology and drug discovery. Secondary metabolites are biosynthesized to benefit the host organism in its environment (feeding deterrence from predators, antibiotic properties to avoid infection, etc.) but these compounds also serve as useful scaffolds in drug discovery applications. The research herein describes both aspects of these two branches of natural products chemistry. The Antarctic sponge Dendrilla membranosa produces diterpenes, of which membranolide A, deters feeding of the predatory amphipod Gondogenia antarctica. A metabolomic study of several sponges was undertaken to determine environmental factors that govern the metabolism of D. membranosa. Habitat specificity, above or below the algal canopy, was a significant factor for the chemical clustering of sponges as well as the abundance of potential amphipod predators that are prevalent within the canopy. Another D. membranosa diterpene, aplysulphurin, undergoes degradation upon methanolic treatment to form the methoxy membranolides B-H. An investigation of these artifacts reveals potent activity against the leishmaniasis-causing parasite Leishmania donovani. Microorganisms also generate a significant number of bioactive natural products. Biotic and abiotic culture stressors such as co-culturing and epigenetic modification, respectively, will be explored to turn on cryptic biosynthetic pathways. These techniques are shown to produce unique secondary metabolites from cultures and further reinforce the one strain many compounds approach to the versatile and formidable microbial domain.

Included in

Chemistry Commons

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