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Title: Clustered Genes Involved in Cyclopiazonic Acid Production are Next to the Aflatoxin Biosynthesis Gene Cluster in Aspergillus flavus

item Chang, Perng Kuang

Submitted to: Fungal Genetics and Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/7/2008
Publication Date: 11/14/2008
Citation: Chang, P.-K., Horn, B.W., Dorner, J.W. 2009. Clustered Genes Involved in Cyclopiazonic Acid Production are Next to the Aflatoxin Biosynthesis Gene Cluster in Aspergillus flavus. Fungal Genetics and Biology. 46:176-182.

Interpretive Summary: Aspergillus flavus populations are diverse. Some isolates of A. flavus produce the carcinogenic aflatoxins and another toxin called cyclopiazonic acid. These two mycotoxins have been reported to co-contaminate agriculture and food commodities. Genes involved in aflatoxin biosynthesis have been well-characterized. However, the study on cyclopiazonic acid biosynthesis is scarce. In the analysis of genome regions adjoining the aflatoxin gene cluster, putative genes associated with cyclopiazonic acid production were identified. Functional studies using a gene knock-out approach confirmed that three genes are involved in cyclopiazonic acid biosynthesis. A. flavus isolates that do not produce cyclopiazonic acid have deletion in one or more of these genes. The nonaflatoxigenic A. flavus NRRL 21882, the active ingredient of the Afla-Guard' biopesticide, was found to have lost the three genes, which further ensures its safe application in peanut fields.

Technical Abstract: Cyclopiazonic acid (CPA), an indole-tetramic acid toxin, is produced by many species of Aspergillus and Penicillium. In addition to CPA Aspergillus flavus produces polyketide-derived carcinogenic aflatoxins (AFs). AF biosynthesis genes form a gene cluster in a subtelomeric region. Isolates of A. flavus lacking AF production due to the loss of the entire AF gene cluster and portions of the subtelomeric region are often unable to produce CPA, which suggests a physical link of genes involved in CPA biosynthesis to the AF gene cluster. Examining the subtelomeric region in A. flavus isolates of different chemotypes revealed a region possibly associated with CPA production. Disruption of three of the four genes present in this region predicted to encode a monoamine oxidase, a dimethylallyl tryptophan synthase, and a hybrid polyketide non-ribosomal peptide synthase abolished CPA production in an aflatoxigenic A. flavus strain. Therefore, some of the CPA biosynthesis genes are organized in a mini-gene cluster that is next to the AF gene cluster in A. flavus that produces AFs and CPA.