CELL REDOX BALANCE, LIPID METABOLISM AND AFLATOXIN BIOSYNTHESIS IN ASPERGILLUS SECT. FLAVI

In Aspergillus parasiticus, oxidative stress produced during conidia germination and fungal growth, regulate aflatoxin synthesis via the expression of the oxidative stress-related transcription factor Apyap1 which promotes the antioxidant defence response of the fungal cell. In A. flavus and A. parasiticus a gene cluster for sugar utilisation (SU) has been found which is co-regulated together with the aflatoxin gene cluster. Many fungal toxins, among which aflatoxins, are members of a large, diversified class of compounds known collectively as polyketides. Acetyl-CoA, both as polyketide starter unit and extender unit via malonyl-CoA formation, is the fundamental building block of most fungal polyketides. The nadA gene, present in the SU cluster, encodes NADH oxidase, an enzyme involved in the conversion of pyruvate to Acetyl-CoA and controlling the NAD+/NADH ratio through the utilisation of O2 present in the cell. Since A. flavus infects primarily the embryo and aleurone layer of maize seeds, which are known to house the majority of seed lipids in this plant, it can be argued that the b-oxidation of seed fatty acids, activated during the infection processes, can supply the aflatoxin building blocks, i.e. the Acetyl-CoA. Further, during maize infection, ROS seems to drive aflatoxin synthesis in A. parasiticus, generating an endogenous hyperoxidant state. A scenario emerges that leads us to hypothesise that the Acetyl- CoA present in the cell, controlled also by NADH oxidase, supplies the building blocks necessary for toxin synthesis that occurs only in the presence of a hyperoxidant state of the cell.