Aspergillus sporulation and mycotoxin production both require inactivation of the FadA G alpha protein-dependent signaling pathway

EMBO J. 1997 Aug 15;16(16):4916-23. doi: 10.1093/emboj/16.16.4916.


The filamentous fungus Aspergillus nidulans contains a cluster of 25 genes that encode enzymes required to synthesize a toxic and carcinogenic secondary metabolite called sterigmatocystin (ST), a precursor of the better known fungal toxin aflatoxin (AF). One ST Cluster (stc) gene, aflR, functions as a pathway-specific transcriptional regulator for activation of other genes in the ST pathway. However, the mechanisms controlling activation of aflR and synthesis of ST and AF are not understood. Here we show that one important level for control of stc gene expression requires genes that were first identified as early acting regulators of asexual sporulation. Specifically, we found that loss-of-function mutations in flbA, which encodes a RGS domain protein, or dominant activating mutations in fadA, which encodes the alpha subunit of a heterotrimeric G protein, block both ST production and asexual sporulation. Moreover, overexpression of flbA or dominant interfering fadA mutations cause precocious stc gene expression and ST accumulation, as well as unscheduled sporulation. The requirement for flbA in sporulation and ST production could be suppressed by loss-of-function fadA mutations. The ability of flbA to activate stc gene expression was dependent upon another early acting developmental regulator, fluG, and AflR, the stc gene-specific transcription factor. These results are consistent with a model in which both asexual sporulation and ST production require inactivation of proliferative growth through inhibition of FadA-dependent signaling. This regulatory mechanism is conserved in AF-producing fungi and could therefore provide a means of controlling AF contamination.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aflatoxins / biosynthesis
  • Aflatoxins / toxicity
  • Aspergillus / genetics
  • Aspergillus / physiology
  • Aspergillus nidulans / genetics
  • Aspergillus nidulans / metabolism
  • Aspergillus nidulans / physiology*
  • Chromatography, Thin Layer
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • GTP-Binding Proteins / metabolism*
  • GTPase-Activating Proteins
  • Gene Expression Regulation, Fungal
  • Genes, Fungal / genetics
  • Mutation
  • Proteins / genetics
  • RNA, Messenger / analysis
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Spores, Fungal / physiology
  • Sterigmatocystin / biosynthesis*
  • Sterigmatocystin / toxicity
  • Transcription, Genetic


  • Aflatoxins
  • FADA protein, Emericella nidulans
  • FLUG protein, Emericella nidulans
  • Fungal Proteins
  • GTPase-Activating Proteins
  • Proteins
  • RNA, Messenger
  • flbA protein, Aspergillus nidulans
  • Sterigmatocystin
  • GTP-Binding Proteins