pH regulation of sterigmatocystin and aflatoxin biosynthesis in Aspergillus spp.

Aflatoxin (AF) and sterigmatocystin (ST) are toxic secondary metabolites produced by the same biochemical pathway found in several Aspergillus spp. The expression of the homologous ST/AF structural gene, stcU in A. nidulans and ver-1 in A. parasiticus, was affected by external pH of liquid growth media. Both stcU and ver-1 mRNAs appeared earlier and were expressed at higher levels in cultures grown in acidic media (pH 4 to 6) versus neutral (pH 7) and alkali (pH 8) media. Transcript levels correlated with ST/AF production. Visual and spectrophotometric analysis of production of the orange ST/AF intermediate, norsolorinic acid (NOR), also paralleled transcript patterns and indicated that the pH effects were operative in different nitrogen- and carbon-based solid growth media. Five- to 10-fold increases in ST, AF, and NOR were measured in cultures grown in pH 4 or 5 versus pH 8 media. An A. nidulans strain carrying a mutation resulting in constitutive activity of the pH regulatory factor, PacC, produced 10-fold less ST than did wild type. The stcU transcript was not noticeably affected by pH in this strain. The results suggest a general pattern of pH regulation of ST/AF biosynthesis that may override previously noted carbon and nitrogen effects.