The diversity, distribution, and biological activity of brominated natural products in the genus Pseudoalteromonas

Secondary metabolite production plays an important role in the interaction of bacteria and their environments. While many marine microbes have been found to produce bioactive molecules, relatively little is known about the diversity and distribution of biosynthetic gene clusters with known products. This dissertation includes five chapters that explore these topics in the genus Pseudoalteromonas. The first chapter introduces marine natural products and the group of bacteria, followed by three research chapters and a summary chapter. Chapter 2 explores the evolution of the bmp gene cluster in the genus Pseudoalteromonas. A well-supported species phylogeny was generated and the distribution and diversity of the biosynthetic gene cluster was mapped onto the tree. Four distinct versions of the bmp cluster were found in the genus, with evidence supporting gene loss in certain cases. It is uncertain how many times the gene cluster was acquired within Pseudoalteromonas, but the conservation of the biosynthetic genes within some lineages suggests that the metabolites produced are relevant to the ecology of these bacteria. Chapter 3 presents the results from the bacterial cytological profiling of pentabromopseudilin in an E. coli strain. The primary phenotype observed in treated cells was membrane permeability, which increases over time and concentration. Despite its apparent ability to disrupt the cell membrane of Gram-negative bacteria and increase the potency of two tested antibiotics, pentabromopseudilin is not likely a good candidate for therapeutic uses due its cytotoxicity. The final research chapter investigates the bioactivity and biosynthetic potential of five Pseudoalteromonas species. The crude extracts and fractions of some of the strains included in the study were bioactive against Gram-positive and Gram-negative test strains. Preliminary genome mining results reveal that Pseudoalteromonas are rich in biosynthetic gene clusters, most of which do not have known products or similar clusters.