25 COREGULATED TRANSCRIPTS DEFINE A STERIGMATOCYSTIN GENE-CLUSTER IN ASPERGILLUS-NIDULANS

Sterigmatocystin (ST) and the aflatoxins (AFs), related fungal seconda ry metabolites, are among the most toxic, mutagenic, and carcinogenic natural products known. The ST biosynthetic pathway in Aspergillus nid ulans is estimated to involve at least 15 enzymatic activities, while certain Aspergillus parasiticus, Aspergillus flavus, and Aspergillus n omius strains contain additional activities that convert ST to AF. We have characterized a 60-kb region in the A. nidulans genome and find i t contains many, if not all, of the genes needed for ST biosynthesis. This region includes verA, a structural gene previously shown to be re quired for ST biosynthesis, and 24 additional closely spaced transcrip ts ranging in size from 0.6 to 7.2 kb that are coordinately induced on ly under ST-producing conditions. Each end of this gene cluster is dem arcated by transcripts that are expressed under both ST-inducing and n on-ST-inducing conditions. Deduced polypeptide sequences of regions wi thin this cluster had a high percentage of identity with enzymes that have activities predicted for ST/AF biosynthesis, including a polyketi de synthase, a fatty acid synthase (alpha and beta subunits), five mon ooxygenases, four dehydrogenases, an esterase, an O-methyltransferase, a reductase, an oxidase, and a zinc cluster DNA binding protein. A re vised system for naming the genes of the ST pathway is presented.