Genetic safeguard against mycotoxin production and cyclopiazonic acid biosynthesis in Aspergillus oryzae

. Aspergillus oryzae is a fungus widely used in traditional Japanese fermentation industries. Its inability to produce mycotoxins, due to mutation or transcriptional repression of genes responsible for their biosynthesis, is consistent with the hypothesis that A . oryzae is a domesticated species derived from A . flavus , a wild species that is a well-known producer of aflatoxin. This review highlights genetic bases for a difference in secondary metabolite production in two closely related species, some of which serve as safeguards against mycotoxin production in A . oryzae . In the course of the analysis of the cyclopiazonic acid biosynthetic gene cluster in A . oryzae , we found another genetic safeguard to ensure the safety of A . oryzae . The cpa cluster in A . oryzae contains genes that have been lost in A . flavus , one of which, cpaH , mediates the conversion of cyclopiazonic acid into the less toxic 2 -oxo-cyclopiazonic acid. The detoxi-fying property of cpaH reflects the relationship of the two species.