Evidence that a transcription factor regulatory network coordinates oxidative stress response and secondary metabolism in aspergilli
Article first published online: 1 JAN 2013
© 2012 The Authors. MicrobiologyOpen published by Blackwell Publishing Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Volume 2, Issue 1, pages 144–160, February 2013
How to Cite
MicrobiologyOpen 2013; 2(1): 144–160
- Issue published online: 13 FEB 2013
- Article first published online: 1 JAN 2013
- Manuscript Accepted: 22 NOV 2012
- Manuscript Revised: 13 NOV 2012
- Manuscript Received: 23 OCT 2012
- National Institutes of Health. Grant Number: RO1 CA52003-21
- Michigan AgBio Research
- Internal Research Grants Program
- Aspergillus parasiticus ;
- oxidative stress;
- reactive oxygen species;
- secondary metabolism
The mycotoxin aflatoxin is a secondary metabolite and potent human carcinogen. We investigated one mechanism that links stress response with coordinate activation of genes involved in aflatoxin biosynthesis in Aspergillus parasiticus. Electrophoretic mobility shift assays demonstrated that AtfB, a basic leucine zipper (bZIP) transcription factor, is a master co-regulator that binds promoters of early (fas-1), middle (ver-1), and late (omtA) aflatoxin biosynthetic genes as well as stress-response genes (mycelia-specific cat1 and mitochondria-specific Mn sod) at cAMP response element motifs. A novel conserved motif 5′-T/GNT/CAAG CCNNG/AA/GC/ANT/C-3′ was identified in promoters of the aflatoxin biosynthetic and stress-response genes. A search for transcription factors identified SrrA as a transcription factor that could bind to the motif. Moreover, we also identified a STRE motif (5′-CCCCT-3′) in promoters of aflatoxin biosynthetic and stress-response genes, and competition EMSA suggested that MsnA binds to this motif. Our study for the first time provides strong evidence to suggest that at least four transcription factors (AtfB, SrrA, AP-1, and MsnA) participate in a regulatory network that induces aflatoxin biosynthesis as part of the cellular response to oxidative stress in A. parasiticus.