Sterigmatocystin (SI) is a carcinogenic polyketide mycotoxin produced by members of the Aspergillus genus. The elucidation of the regulatory pathways that govern mycotoxin synthesis may lead to applications that prevent food crop contamination. This study addresses how carbon from primary metabolism, specifically the acetyl-CoA pool, in Aspergillus nidulans is coordinated and directed into ST biosynthesis. The production of ST appears to be sensitive to alterations in peroxisome function and gluconeogensis, but it is not clear how these effects are being exerted. The impacts of peroxisome proliferation and gluconeogenesis defects on the flow of carbon through the known primary and secondary metabolic pathways of this organism will be assessed at the level of gene expression. A microarray system that represents a subset of A. nidulans genes that serve as metabolic markers will be developed. Additionally, the contribution of peroxisomal Beta-oxidation (Beta-ox) to the acetyl-CoA pool available to ST biosynthesis will be assessed through the construction of Beta-ox mutants, by correlating the induction of Beta-ox with the onset of ST synthesis, and with labeling studies. Besides identifying possible control points for mycotoxin production in the field, these studies should offer an unprecedented view of how primary and secondary metabolic pathways are coordinated.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI052654-03
Application #
6751493
Study Section
Special Emphasis Panel (ZRG1-F08 (20))
Program Officer
Duncan, Rory A
Project Start
2002-07-01
Project End
2005-03-31
Budget Start
2004-07-01
Budget End
2005-03-31
Support Year
3
Fiscal Year
2004
Total Cost
$38,071
Indirect Cost
Name
University of Wisconsin Madison
Department
Other Basic Sciences
Type
Schools of Earth Sciences/Natur
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Maggio-Hall, Lori A; Lyne, Paul; Wolff, Jon A et al. (2008) A single acyl-CoA dehydrogenase is required for catabolism of isoleucine, valine and short-chain fatty acids in Aspergillus nidulans. Fungal Genet Biol 45:180-9
Maggio-Hall, Lori A; Wilson, Richard A; Keller, Nancy P (2005) Fundamental contribution of beta-oxidation to polyketide mycotoxin production in planta. Mol Plant Microbe Interact 18:783-93
Maggio-Hall, Lori A; Keller, Nancy P (2004) Mitochondrial beta-oxidation in Aspergillus nidulans. Mol Microbiol 54:1173-85