Analysis of a mycotoxin gene cluster in Aspergillus nidulans

Abstract

Aspergillus nidulans has functioned as a model system for the study of fungal genetics since the 1950s. Application of methodologies ranging from Mendelian genetics to the most sophisticated molecular biological techniques have resulted in a detailed understanding of genes and pathways involved in primary metabolism, secondary metabolism and development in A. nidulans. We have taken advantage of this background in developing A. nidulans as a genetic system to study the molecular mechanisms regulating aflatoxin biosynthesis. Aflatoxin, a carcinogenic polyketide, is the product of a lengthy biochemical pathway found in the asexual spp., A. flavus and A. parasiticus. A. nidulans possesses most if not all of this pathway and produces sterigmatocystin, the penultimate precursor of the aflatoxin pathway. We have identified a approximately 60 kb cluster of genes in A. nidulans whose products are involved in sterigmatocystin biosynthesis. This cluster contains at least 20 genes proposed to encode both enzymatic activities and regulatory proteins. Our results have shown that at least some of these genes are functionally conserved between A. nidulans, A. flavus and A. parasiticus, and that they are regulated in similar ways. Further studies of sterigmatocystin regulation in A. nidulans should yield information transferable to studies of (i) secondary metabolism in other filamentous fungi and (ii) aflatoxin regulation in A. flavus and A. parasiticus in particular.