Program Project on Mining the Aspergillus nidulans Secondary Metabolome
Infectious disease is the second leading cause of death worldwide. The increasing number of drug resistant microbes exacerbates this health problem. Antimicrobial discovery began with the fortuitous discovery of penicillin production by the fungus Penicillium and, soon after, many more natural products, most often bacterially derived, were identified and implemented in disease treatment.
The primary goal of this Program Project was to identify and purify potentially useful secondary metabolites of the filamentous fungus Aspergillus nidulans.
The project was taking advantage of recent progress in gene targeting in A. nidulans to create a set of molecular genetic tools and strains that would allow the efficient exploitation of the A. nidulans secondary metabolome. This project had three Aims:
- to create a set of transformants that will allow the products of all A. nidulans secondary metabolism gene clusters to be identified.
- to delete genes of selected secondary metabolism pathways to allow the steps of the pathways to be clarified and shunt products isolated.
- to develop promoter replacement strains that will allow increased expression of secondary metabolism pathways.
Dr. Berl Oakley, KU
Using the sequenced model ascomycete Aspergillus nidulans, the project had three aims:
1. To activate global secondary metabolite regulators able to genetically manipulate the fungus into prime metabolite production.
2. To develop genetic tools for increased secondary metabolite production in fungi.
3. To transition the newly identified compounds in aims 1 and 2 to bioassays of major groups of fungal and bacterial pathogens.
Dr. Nancy Keller, University of Wisconsin
The goal of this Project was to chemically identify each of the 40+ secondary metabolites and their corresponding biosynthetic gene clusters that the fungus Aspergillus nidulans is capable of producing.
Dr. Clay Wang, University of Southern California
- Dr. Berl Oakley, Irving S. Johnson Distinguished Professor of Molecular Biology, Department of Molecular Biosciences, University of Kansas: Project Leader
- Christine Oakley: Assistant Researcher
- Dr. Ruth Entwistle: Assistant Researcher
- Dr. Nancy Keller Professor, Department of Medical Microbiology & Immunology, University of Wisconsin, Madison: Project Leader
- Dr. Jin Woo Bok, U of Wisconsin, Madison: Postdoc
- Dr. Clay Wang, Assistant Professor, Department of Pharmacology and Pharmaceutical Sciences, University of Southern California: Project Leader
- Dr. Yi Ming Chiang, University of Southern California: Postdoc