Submitted to: Applied Microbiology and Biotechnology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/15/2006
Publication Date: 1/14/2007
Citation: Duran, R.M., Cary, J.W., Calvo, A.M. 2007. Production of cyclopiazonic acid, aflatrem and aflatoxin by Aspergillus flavus is regulated by veA, a gene necessary for sclerotial formation. Applied Microbiology and Biotechnology. 73(5):1158-1168. Interpretive Summary: This work describes experiments that have been conducted in an effort to better understand the genetic mechanisms that control aflatoxin production and growth and development in Aspergillus flavus. Aflatoxins are toxic and carcinogenic compounds often produced by the fungi, Aspergillus flavus, during growth on crops such as corn, peanuts, cottonseed, and treenuts. Because of the potential health risks, aflatoxin contamination of food and feed crops is also of great economic importance to farmers who cannot sell their crops due to strict domestic and international regulatory guidelines with regards to aflatoxin contamination. We have succeeded identifying a gene, designated veA, from A. flavus, that when inactivated, stops the fungus from producing aflatoxin and also structures known as sclerotia that help the fungus to survive in the field under adverse conditions. In addition, this study showed that veA also controls the production of two other known toxins in A. flavus, cyclopiazonic acid and aflatrem. We can now use what we have learned from these studies to try and identify other A. flavus genes that are part of the veA control circuit and use this knowledge to aid in unraveling the mechanisms responsible for production of aflatoxin and other A. flavus toxins. This in turn will help in devising strategies for eliminating fungal toxin contamination of food and feed crops.
Technical Abstract: The plant pathogenic fungus, Aspergillus flavus, produces several types of mycotoxins. The most well known are the carcinogenic compounds called aflatoxins. In addition, A. flavus produces cyclopiazonic acid and aflatrem mycotoxins, contributing to the toxicity of A. flavus infected crops. Cyclopiazonic acid is a specific inhibitor of calcium-dependent ATPase in the sarcoplasmic reticulum that results in altered cellular Ca++ levels. Aflatrem is a potent tremogenic mycotoxin known to lead to neurological disorders. Previously, we showed that a gene called veA controls aflatoxin and sclerotial production in Aspergillus parasiticus. In this study in A. flavus, we show that the veA homolog in A. flavus not only is necessary for the production of aflatoxins B1 and B2 and sclerotia, but also regulates the synthesis the mycotoxins cyclopiazonic acid and aflatrem. The Aspergillus flavus veA mutant was completely blocked in the production of aflatrem and showed greater than 2-fold decrease in cyclopiazonic acid production. The genes involved in the synthesis of cyclopiazonic acid are unknown, however the aflatrem gene cluster has been characterized. Northern hybridization analysis showed that veA is required for expression of the A. flavus aflatrem genes, atmC, atmG, and atmM. This is the first report of a regulatory gene governing the production of cyclopiazonic acid and aflatrem mycotoxins.