Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 3/15/2004
Publication Date: 5/12/2004
Citation: Yu, J., Cleveland, T.E., Bhatnagar, D. 2004. Genetic and biochemical studies on the mechanisms of aflatoxin biosynthesis [abstract]. 7th European Conference on Fungal Genetics and 1st Aspergillus Workshop, April 17-21, 2004, Copenhagen, Denmark. Interpretive Summary:
Technical Abstract: Aflatoxins B1, B2, G1, and G2 are secondary metabolites produced primarily by the filamentous fungi, Aspergillus flavus and A. parasiticus. These toxins are the most carcinogenic and toxic natural compounds that contaminate foods and feed. Due to the health risk of aflatoxins posed on human and livestock, research on the genetics and biochemistry of aflatoxin biosynthesis has been carried out in great detail. The biosynthesis of aflatoxins is a multi-enzymatic process consisting of at least 16 structurally defined intermediates. Studies on the molecular mechanism of aflatoxin biosynthesis in this laboratory have identified an aflatoxin pathway gene cluster of 70 kilobase pairs in length consisting of at least 25 identified genes including a positive regulatory gene as transcription activator. In addition, a sugar utilization gene cluster consisting of four genes and a nitrogen utilization gene cluster consisting of two genes have also been cloned. The completed DNA sequence of the aflatoxin gene cluster has been determined and the genes involved in aflatoxin formation have been systematically renamed from aflA to aflY according to the gene convention in Aspergillus. They are: aflA (fas-2), aflB (fas-1), aflC (pksA), aflD (nor-1), aflE (norA), aflF (norB), aflG (avnA), aflH (adhA), aflI (avfA), aflJ (estA), aflK (vbs), aflL (verB), aflM (ver-1), aflN (verA), aflO (omtB), aflP (omtA), aflQ (ordA), aflR (aflR), aflS (aflJ), aflT (aflT), aflU (cypA), aflV (cypX), aflW (moxY), aflX, aflY. Gene profiling studies in A. flavus by Expressed Sequenced Tag (EST) and microarray have identified many genes that are potentially involved in aflatoxin formation among over 7,000 unique ESTs sequenced. These include genes directly involved in aflatoxin biosynthesis; regulation and signal transduction; genes that have the potential to contribute to fungal virulence or pathogeneicity; and genes involved in fungal development. Functional genomics studies using microarray under different conditions are underway. The goal of this research is aimed at providing information for developing new strategies for control of aflatoxin contamination of agricultural commodities. The functions of these pathway genes, their expressional regulation and cluster organization in comparison with the sterigmatocystin pathway gene cluster in A. nidulans will be presented.