PEROXISOME FUNCTIONALITY, LIPID METABOLISM AND OXIDATIVE STRESS AFFECT AFLATOXIN BIOSYNTHESIS AND DEVELOPMENT IN ASPERGILLUS FLAVUS

Oxidative stress occurs in all the organisms during metabolic pathways such as β-oxidation of fatty acids. In aflatoxigenic fungi, this process is able to create the two main pre-requisites for aflatoxin synthesis, i.e. acetyl-CoA and an hyper oxidant status of the cell. The β-oxidation of long chain fatty acids in fungi occurs in peroxisomes, which also have a role in the scavenging abilities of the fungal cell. In order to demonstrate a correlation between peroxisome functionality, lipid metabolism, cell redox balance and aflatoxin synthesis, a gene of Cymbidium ringspot virus encoding a protein, p33, able to induce peroxisome proliferation, was inserted in A. flavus NRRL 3357. Afp33GFPdsRED presents an up-regulation of the lipid metabolism and of the TCA cycle which probably leads to a hyper oxidant status (higher ROS and 9-oxylipins formation) in the cell. These events trigger aflatoxin biosynthesis both in vitro and also when Afp33GFPdsRED was inoculated on its natural host, i.e. in maize seeds. How peroxisome proliferation, lipid oxidation and oxidative stress, are able to modulate aflatoxin biosynthesis? In silico N_SITE software analysis of the promoter region of the aflatoxin regulator aflR indicates the presence of regulatory elements (RE) responsive to SREBP-ADD1, AP1, and PPARα binding factors which are involved in the modulation of lipid metabolism, oxidative stress and peroxisome proliferation in animals. A scenario emerges in which the creation of an oxidative cell environment and the generation of signal molecules (e.g. oxylipins), related to peroxisomes activity, are able to modulate aflatoxin synthesis by affecting aflR transcription.