Abstract
Aflastatin A (AsA) is an inhibitor of aflatoxin production by Aspergillus parasiticus and it also inhibits production of other polyketide metabolites by fungi such as melanin produced by Colletotrichum lagenarium. To elucidate the mode of action of AsA, the effect of AsA on the biosynthetic pathway of each aflatoxin and melanin was examined. AsA inhibited production of norsolorinic acid, an early biosynthetic intermediate of aflatoxin. The transcription of genes encoding some aflatoxin biosynthetic enzymes and a gene encoding a regulatory protein for expression of the biosynthetic enzymes (aflR) were significantly reduced by the addition of AsA. These results suggest that AsA inhibits a very early step in aflatoxin biosynthesis prior to the transcription of aflR. On the other hand, AsA inhibited the production of scytalone, an intermediate of melanin biosynthesis, and it severely impaired the expression of PKS1 encoding a melanin biosynthetic enzyme. This suggests that AsA inhibits an early step in melanin production similarly to the case in aflatoxin production. We also found that AsA elevated the glucose consumption and ethanol accumulation by A. parasiticus, which suggested that AsA can influence glucose metabolism in the fungus.
