Submitted to: Book Chapter
Publication Type: Book / Chapter
Publication Acceptance Date: March 17, 2011
Publication Date: September 9, 2011
Citation: Ehrlich, K., Chang, P.-K., Yu, J., Cary, J.W., Bhatnagar, D. 2011. Control of aflatoxin biosynthesis in Aspergilli. In: Guevara-Gonzalez, R.G., editor. Aflatoxins - Biochemistry and Molecular Biology. Rijeka, Croatia: Intech Open Access Publishers. pp 21-40. Interpretive Summary: Aflatoxin in a toxin and carcinogenic fungal metabolite that can be a food contaminant. In this review we provide the current knowledge about how aflatoxin production is controlled by different processes in the fungal cell. In order to make aflatoxin the fungus has to turn-on the genes that are necessary for making the proteins required for synthesizing the molecule. There are many steps required for the process of turning on the genes. The DNA has to be made active. This is a process requiring several types of proteins called, pathway-specific transcription factors, global transcription factors, and transcriptional co-activators. Once transcription is turned on, the process is still not finished, but requires helper proteins to activate the proteins need for the toxin synthesis, and additional proteins to guide the toxin synthesis proteins to the right places in the cell. For all this to happen there are initiating factors and messengers, usually on the fungal cell surface that receive the signal that says: “start aflatoxin synthesis”. This review gives a summary of these processes.
Technical Abstract: Expression of the genes in the AF biosynthesis cluster is mainly controlled by the pathway specific Cys6Zn2 DNA binding protein, AflR. While AflR appears to be necessary for the activation, a number of coactivators are important for fine-tuning of the timing of AflR’s activity. These proteins, AflJ, LaeA, VeA, VelB and VosA, may form a complex in the nucleus to not only position AflR at the AF cluster genes but also alter the chromatin conformation in this locus in order to allow AflR and global transcriptional regulatory proteins to make contact with the basal transcription machinery. They may do this concomitantly with AflR binding or act to recruit AflR to the cluster. AflR expression is induced by simple sugars and inhibited by certain organic acids and aldehydes. Globally acting DNA-binding proteins are involved in transmitting the nutritional or environmental signal to the activation of the AF gene cluster. A signaling cascade involving cAMP-dependent protein kinase A plays a role in the activation. The regulatory models shown in Figures 1 and 6 resemble that for expression of developmentally regulated genes in yeast and other fungi.