University of Southern California Dissertations and Theses

Secondary metabolites biosynthesis in Aspergillus species revealed by fungal genome mining

(USC Thesis Other)

Secondary metabolites biosynthesis in Aspergillus species revealed by fungal genome mining

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Abstract (if available)

Abstract Filamentous fungi, such as species found within the genus Aspergillus, are known to produce a wide variety of secondary metabolites. Genome sequencing of members of the genus Aspergillus revealed that there are far more secondary metabolite gene clusters than known secondary metabolites. This suggests that many more secondary metabolites could be discovered from these organisms. Development of an efficient gene targeting system in A. nidulans greatly facilitated the genome mining studies of this species. Application of this system allowed us to identify two separate clusters that are responsible for the biosynthesis of one type of meroterpenoids austinol and dehydroaustinol. Further characterization of a homologous cluster for terretonin biosynthesis in A. terreus reveals that this cluster shares high homology with the two austinol clusters, suggesting they may share the same ancestral gene cluster. ❧ To further explore the secondary metabolites of this lovastatin-producing A. terreus strain, we individually developed an efficient gene targeting system in this fungus. Using this tool we could efficiently link four major types of secondary metabolites in A. terreus with their core synthesis genes. Since fungal secondary metabolite genes are clustered, we also efficiently characterized two clusters, one for terreic acid biosynthesis and one for acetylaranotin biosynthesis. ❧ Furthermore, our studies demonstrate the added complexity of fungal secondary metabolite biosynthesis. Regarding the cluster hypothesis, there are exceptions when the clusters for two unrelated natural products, fumagilin and pseurotin A, are physically intertwined with each other and coregulated by the same regulatory gene resided in this “super cluster”. Besides, we found that in a single organism, two different genes could synthesize the same compound Aspulvinone E in different fungal tissues. And this site-directed biosynthesis is probably regulated by the promoters of these two genes, rather than the genes themselves or their encoding proteins.

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Asset Metadata

Creator Guo, Chun-Jun (author)

Core Title Secondary metabolites biosynthesis in Aspergillus species revealed by fungal genome mining

School School of Pharmacy

Degree Doctor of Philosophy

Degree Program Pharmaceutical Sciences

Publication Date 03/31/2015

Defense Date 10/14/2014

Publisher University of Southern California (original), University of Southern California. Libraries (digital)

Tag fungal secondary metabolites,genome mining,natural product chemistry,OAI-PMH Harvest

Format application/pdf (imt)

Language English

Contributor Electronically uploaded by the author (provenance)

Advisor Wang, Clay C.C. (committee chair), Olenyuk, Bogdan (committee member), Williams, Travis J. (committee member)

Creator Email chunjung@usc.edu,chunjung19@gmail.com

Permanent Link (DOI) https://doi.org/10.25549/usctheses-c3-542638

Unique identifier UC11297284

Identifier etd-GuoChunJun-3243.pdf (filename),usctheses-c3-542638 (legacy record id)

Legacy Identifier etd-GuoChunJun-3243.pdf

Dmrecord 542638

Document Type Dissertation

Format application/pdf (imt)

Rights Guo, Chun-Jun

Type texts

Source University of Southern California (contributing entity), University of Southern California Dissertations and Theses (collection)

Access Conditions 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 a...

Repository Name University of Southern California Digital Library

Repository Location USC Digital Library, University of Southern California, University Park Campus MC 2810, 3434 South Grand Avenue, 2nd Floor, Los Angeles, California 90089-2810, USA