Biosynthesis of Ochratoxin A in Aspergillus westerdijkiae

Orchratoxins are some of the most abundant mycotoxins known to contaminate cereals and are hazards to public health. Details are still missing about the exact biosynthetic and regulatory mechanism for this potent carcinogen. Fungi belonging to the genera Aspergillus and Penicillium are the major producers of Ochratoxins in the natural environment. Advances in genome sequencing and bioinformatic tools have made the genome based approach of secondary metabolism (SM) gene cluster discovery a method of choice. We sequenced the whole genome of Aspergillus westerdijkiae CBS112803 which is known to produce a variety of interesting secondary metabolites including Ochratoxin A (OTA). The genome data revealed the presence of a putative OTA synthesis cluster and we further validated the function of this putative  cluster with a series of gene knockout experiments.

     Regulation of secondary metabolism is another aspect that is complex and less understood. A number of SM gene clusters remain cryptic under laboratory conditions. While, few of these clusters involve one or more transcription factors and other regulatory genes, some function under the influence of a universal regulator. Here, we report the role of a bZIP transcription factor associated to the OTA cluster, acting as an activator of OTA synthesis in Aspergillus westerdijkiae CBS112803. Our   studies  have  confirmed   that the deletion of this gene not only eliminates OTA synthesis but is also found to affect other phenotypes such as pigmentation and spore formation, which may provide insight for rational drug / inhibitor design.