bZIP transcription factors affecting secondary metabolism, sexual development and stress responses in Aspergillus nidulans

The eukaryotic basic leucine zipper (bZIP) transcription factors play critical roles in the organismal response to the environment. Recently, a novel YAP-like bZIP, restorer of secondary metabolism A (RsmA), was found in a suppressor screen of an Aspergillus nidulans secondary metabolism (SM) mutant in which overexpression of rsmA was found to partially remediate loss of SM in Velvet Complex mutants. The Velvet Complex is a conserved fungal transcriptional heteromer that couples SM with sexual development in fungi. Here we characterized and contrasted SM in mutants of RsmA and four other A. nidulans bZIP proteins (NapA, ZipA, ZipB and ZipC) with predicted DNA binding motifs similar to RsmA. Only two overexpression mutants exhibited both SM and sexual abnormalities that were noteworthy: OE: : rsmA resulted in a 100-fold increase in sterigmatocystin and a near loss of meiotic spore production. OE: : napA displayed decreased production of sterigmatocystin, emericellin, asperthecin, shamixanthone and epishamixanthone, coupled with a shift from sexual to asexual development. Quantification of bZIP homodimer and heterodimer formation using fluorescence resonance energy transfer (FRET) suggested that these proteins preferentially self-associate.