Abstract

Suppressor Mutagenesis Identifies a Velvet Complex Remediator of Aspergillus nidulans Secondary Metabolism ▿ † Mona I. Shaaban 1 , 2 , Jin Woo Bok 1 , Carrie Lauer 1 and Nancy P. Keller 1 , 3 , * 1 Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, Wisconsin 2 Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Egypt 3 Department of Bacteriology, University of Wisconsin-Madison, Madison, Wisconsin ABSTRACT Fungal secondary metabolites (SM) are bioactive compounds that are important in fungal ecology and, moreover, both harmful and useful in human endeavors (e.g., as toxins and pharmaceuticals). Recently a nuclear heterocomplex termed the Velvet complex, characterized in the model ascomycete Aspergillus nidulans , was found to be critical for SM production. Deletion of two members of the Velvet complex, laeA and veA , results in near loss of SM and defective sexual spore production in A. nidulans and other species. Using a multicopy-suppressor genetics approach, we have isolated an Aspergillus nidulans gene named rsm A (remediation of secondary metabolism) based upon its ability to remediate secondary metabolism in Δ laeA and Δ veA backgrounds. Overexpression of rsmA (OE:: rsmA ) restores production of sterigmatocystin (ST) (a carcinogenic SM) via transcriptional activation of ST biosynthetic genes. However, defects in sexual reproduction in either Δ laeA or Δ veA strains cannot be overcome by OE:: rsmA . An intact Velvet complex coupled with an OE:: rsmA allele increases SM many fold over the wild-type level, but loss of rsmA does not decrease SM. RsmA encodes a putative bZIP basic leucine zipper-type transcription factor.