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MOLECULAR GENETIC MINING OF THE SECONDARY METABOLOME IN
ASPERGILLUS NIDULANS
by
Hsien-Chun Lo
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(PHARMACEUTICAL SCIENCES)
August 2012
Copyright 2012 Hsien-Chun Lo
Object Description
| Title | Molecular genetic mining of the secondary metabolome in Aspergillus nidulans |
| Author | Lo, Hsien-Chun |
| Author email | hsienchl@usc.edu;usckenlo@gmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Pharmaceutical Sciences |
| School | School of Pharmacy |
| Date defended/completed | 2012-05-29 |
| Date submitted | 2012-07-25 |
| Date approved | 2012-07-25 |
| Restricted until | 2012-07-25 |
| Date published | 2012-07-25 |
| Advisor (committee chair) | Wang, Clay C.C. |
| Advisor (committee member) |
Roberts, Richard W. Olenyuk, Bogdan |
| Abstract | Natural products (secondary metabolites) are an abundant source of bioactive compounds. These small molecules play substantial roles in modern drug development. Aspergillus, a member of filamentous fungi, can produce a range of natural products. This genus has been known for a long time for its medical and commercial importance. In recent years, the genomes of several species of the genus Aspergillus have been fully sequenced. Surprisingly, the genome sequence data reveal that the number of putative secondary metabolite pathways largely overtake the number of natural products that have been isolated and identified from Aspergillus. This discrepancy is a result of the fact that most biosynthetic genes remain silent under standard laboratory culture conditions. The sequence data of A. nidulans along with the development of efficient gene targeting approaches in this specie greatly facilitate the investigation of secondary metabolite biosynthesis. The work presented herein demonstrates the power of a combination of bioinformatics, molecular gene targeting and natural product chemistry approaches in secondary metabolite biosynthesis research. The study subjects include the biosynthesis of emericellamides and austionl/dehydroaustionl in A. nidulans. In addition, epigenetic regulation in activating silent secondary metabolites was also described herein, as deletion of cclA which encodes a crucial component of the COMPASS protein complex, a chromatin modifier, in A. nidulans, led to the discovery of several secondary metabolites. |
| Keyword | Secondary metabolites; Natural product |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m |
| Contributing entity | University of Southern California |
| Rights | Lo, Hsien-Chun |
| Physical access | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@dots.usc.edu |
| Archival file | uscthesesreloadpub_Volume4/etd-LoHsienChu-987.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@dots.usc.edu |
| Full text | MOLECULAR GENETIC MINING OF THE SECONDARY METABOLOME IN ASPERGILLUS NIDULANS by Hsien-Chun Lo A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (PHARMACEUTICAL SCIENCES) August 2012 Copyright 2012 Hsien-Chun Lo |
