1Universití La Sapienza, Roma, Italy, 2North Carolina State University, Raleigh, United States, 3CNR, Roma, Italy Oxidative stress represents a trigger for different metabolic events in all organisms and occurs during oxidative processes in the cell such as glucose oxidation and 61538;-oxidation of fatty acids. In aflatoxigenic fungi these processes are able to supply the aflatoxin building blocks i.e. the acetyl-CoA and an oxidative cell environment, which is necessary for the formation of precursors of aflatoxins. In fact among the several enzyme-catalysed reactions in aflatoxin biosynthesis, at least 6 are represented by oxidative transformations. In order to demonstrate a correlation between cell redox balance, lipid metabolism and aflatoxin synthesis we used WT and mutant strains of Aspergillus parasiticus (NRRL 2999) and of A. flavus (NRRL 3357), aflatoxin producers. A null mutant approach was used for studying the involvement of the oxidative stress related transcription factor ApyapA (Yap1 ortholog) in toxin biosynthesis in A. parasiticus. To study how lipid metabolism is related to aflatoxin formation, a gene (controlled by the Cu,Zn sod promoter of A. flavus) encoding for a viral (Cymbidium Ringspot Virus) protein, P33, which is able to induce peroxisome proliferation, was inserted in A. flavus. Further, in order to find a more direct link among oxidative stress perception, lipid metabolism and aflatoxin biosynthesis, an in silico analysis of the promoter of the aflatoxin gene regulator AflR using the N_SITE tool of softberry software (www.softberry.com) was carried out. In A. parasiticus, oxidative stress, via the activation of the oxidative stress related transcription factor ApyapA, regulates conidiogenesis and aflatoxin synthesis whereas an up-regulation of the lipid metabolism (FFA 61538;-oxidation and TG accumulation) induces a hyperoxidant status and aflatoxin biosynthesis enhancement in A. flavus. In silico N_SITE analysis indicates the presence of regulatory elements (RE) responsive to CREB (cAMP), SREBP-ADD1 (lipid and glucose metabolism), AP1 (human ortholog of Yap1 and ApyapA), PPAR61537; (lipid metabolism) binding factors. It emerges a scenario in which carbon source availability, the turnover of lipids and the cell redox balance can modulate aflatoxin synthesis by affecting aflR transcription, furnishing acetate blocks and creating an oxidative cell environment.
Full conference title:
9th EUROPEAN CONFERENCE ON FUNGAL GENETICS
- ECFG 9th (2008)