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MICROBIAL GENOME MINING IN UNDERSTANDING HUMAN BACTERIAL PATHOGENESIS AND CYANOBACTERIAL NATURAL PRODUCTS BIOSYNTHESIS

Kwak, Daniel H (2016) MICROBIAL GENOME MINING IN UNDERSTANDING HUMAN BACTERIAL PATHOGENESIS AND CYANOBACTERIAL NATURAL PRODUCTS BIOSYNTHESIS. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Recent accessibility of microbial genome sequencing data has enabled broad investigations into the nature of microbial physiology and their consequences on humans and their environment. Through an approach known as genome mining, an in silico technique that enables the identification of uncharacterized gene clusters based on sequence homology, the investigations described herein provide new insight into two important groups of microbes, namely human bacterial pathogens and cyanobacteria. In Part I of this dissertation, genome mining techniques have identified two evolutionarily-conserved cryptic biosynthetic operons in the human pathogens Acinetobacter baumannii and Pseudomonas aeruginosa. Interestingly, the findings demonstrate the significance of these gene clusters and their small molecule products to be important contributors to the pathogenesis of these organisms. As a result, the proteins encoded by these gene clusters are expected to be important targets in the development of next-generation antibiotics. In Part II, a novel platform for the investigation of natural products biosynthesis from cyanobacteria is described. Cyanobacteria have proven to be important yet relatively unexplored sources of bioactive compounds. Recent genome sequencing has indicated the substantial potential of these microbes to synthesize compounds that can be developed into new medicines. The collective findings in this dissertation demonstrate the considerable utility of emerging microbial genome sequencing information and its future impact on human health and disease.


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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Status: Unpublished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 MemberShanks, Robert M. Q.shanksrm@upmc.eduRMS68
Committee MemberDeiters, Alexanderdeiters@pitt.eduDEITERS
Committee MemberWeber, Stephen Gsweber@pitt.eduSWEBER
Date: 21 January 2016
Date Type: Publication
Defense Date: 20 November 2015
Approval Date: 21 January 2016
Submission Date: 3 December 2015
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Number of Pages: 275
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Cyanobacteria, Genome mining, Microbial Secondary Metabolites, Human bacterial pathogens, Natural products biosynthesis, Heterologous expression
Date Deposited: 21 Jan 2017 06:00
Last Modified: 21 Jan 2017 06:00
URI: http://d-scholarship.pitt.edu/id/eprint/26557

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