Submitted to: Toxins
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/23/2009
Publication Date: 9/25/2009
Citation: Ehrlich, K. 2009. Predicted roles of the uncharacterized clustered genes in aflatoxin biosynthesis. Toxins. 1:37-58
Interpretive Summary: Aflatoxin (AF) is a very toxic and carcinogenic fungal compound that is found as a contaminant of corn, cottonseed, peanuts and tree nuts. Our goal is to find key target genes that may allow simple strategies to prevent preharvest AF contamination. If we can interrupt the function of one of the genes unique to fungi, the proteins required for aflatoxin production will not be made, and we will avoid serious complications of toxicity to humans by the intervention strategy. We now report the identification of genes in AF biosynthesis that were not previously characterized. Our results indicate that some of these proteins, in particular the ones made by the genes hypD and avfA could make suitable targets because these proteins are only found in fungi and inhibition of protein function causes a complete loss in the ability of the fungi to make AF.
Technical Abstract: This review discusses the probable roles of hypB, hypC, hypD, hypE, avfA (aflI), aflE, aflF, and aflJ (aflS) in aflatoxin biosynthesis. Based on knockout mutants and E. coli expressing some of the genes, we demonstrate that hypC catalyzes the oxidation of norsolorinic acid anthrone, hypB, the second oxidation step in conversion of O-methylsterigmatocystin to aflatoxin, and hypE, and aflE, the final two steps in AFB1 formation from the HypB precursor. The enzyme encoded by avfA catalyzes the ring-closure step in formation of hydroxyversicolorone that follows CypX oxidation of averufin. We deduce a novel regulatory role for the protein encoded by aflJ, previously shown to bind to AflR, based on its having a partial methyltransferase domain.