%A Daniel H Kwak
%T MS Thesis (ETD) Dan Kwak
%X Microbial secondary metabolites are physiologically significant, exhibiting auxiliary functions for the producer and as scaffolds in the developments of new medicines. Advancements in genome sequencing technologies have enabled researchers to access unprecedented amounts of genomic data that can be used to discover the enzymatic machinery necessary to discover novel and biologically-active molecules. This approach has been termed ?genome mining.? In both of the investigations presented herein, genome mining was utilized to discover and characterize biosynthetic pathways of novel molecules. The findings in one study utilize this approach to discover a small molecule virulence factor from the opportunistic human pathogen Acinetobacter baumannii. This virulence factor has been found to be associated with a number of clinically significant phenotypes, and these findings suggest that this can be a target in the developments of next generation antibiotics. In another study, this approach was implemented to discover and characterize the biosynthetic pathway of anticancer compound hapalosin from the cyanobacterial species Hapalosiphon welwitschii. Cloning and expression of this biosynthetic pathway in the surrogate host Escherichia coli enabled its genetic characterization as well as the generation of a small combinatorial library consisting of analogs incorporating natural and unnatural substrates. Collectively, these investigations demonstrate the utility of genome mining to characterize novel molecules important in pathogenesis or in the biosynthesis of clinically-significant compounds.
%D 2015
%K Discovery of microbial chemicals of clinical significance
%I University of Pittsburgh
%L pittir24587