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MS Thesis (ETD) Dan Kwak

Kwak, Daniel H (2015) MS Thesis (ETD) Dan Kwak. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

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.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Kwak, Daniel Hdhk19@pitt.eduDHK19
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairLiu, Xinyuxinyuliu@pitt.eduXINYULIU
Committee MemberDeiters, Alexanderdeiters@pitt.eduDEITERS
Committee MemberWeber, Stephen Gsweber@pitt.eduSWEBER
Date: 8 June 2015
Date Type: Publication
Defense Date: 25 April 2015
Approval Date: 8 June 2015
Submission Date: 7 April 2015
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Number of Pages: 85
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Discovery of microbial chemicals of clinical significance
Date Deposited: 08 Jun 2015 20:32
Last Modified: 15 Nov 2016 14:27
URI: http://d-scholarship.pitt.edu/id/eprint/24587

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