title: Inhibition of aflatoxin metabolism and growth of Aspergillus flavus in liquid culture by a DNA methylation inhibitor.
abstract: Aflatoxins (AFs) are a group of highly oxygenated polyketidese-derived toxins mainly produced by Aspergillus flavus and A. parasiticus, whose biosynthesis mechanisms are extremely sophisticated. Methylation is known as the major form of epigenetic regulation, which is correlated with gene expression. As the DNA methylation inhibitor 5-azacytidine (5-AC) blocks AF production, we studied AFB1 metabolism and morphological changes of A. flavus by treatment with 5-AC in liquid culture. The results show that 5-AC caused a decrease in AF production and concurrent changes in morphology. In addition, we isolated a non-aflatoxigenic mutant of A. flavus, showing a significant reduction in pigment production, after 5-AC treatment. This mutant showed significant reduction in the expression of genes in the AF biosynthesis pathway, and conidia formation. Furthermore, as AF biosynthesis and oxidative stress are intimately related events, we assessed the viability of A. flavus to oxidative stress after treatment with 5-AC, which showed that the mutant was more sensitive to the strong oxidant hydrogen peroxide. We found that the non-aflatoxigenic mutant showed a decrease in reactive oxygen species (ROS) and metabolites indicative of oxidative stress, which may be caused by the disruption of the defence system against excessive ROS formation after 5-AC treatment. These data indicate that 5-AC, as an inactivator of DNA methyltransferase, plays a very important role in AFB1 metabolism and the development of A. flavus, which might provide an effective strategy to pre- or post-harvest control of AFs.
authors.affiliation: a Key Laboratory of Pathogenic Fungi and Mycotoxins of Fujian Province, The Ministry of Education Key Laboratory of Biopesticide and Chemical Biology , School of Life Sciences, Fujian Agriculture and Forestry University , Fuzhou , China.
authors.forename: Kunlong
authors.initials: K
authors.lastname: Yang
authors.forename: Zhenhong
authors.initials: Z
authors.lastname: Zhuang
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Fengqin
authors.initials: F
authors.lastname: Song
authors.forename: Hong
authors.initials: H
authors.lastname: Zhong
authors.forename: Fanlei
authors.initials: F
authors.lastname: Ran
authors.forename: Song
authors.initials: S
authors.lastname: Yu
authors.forename: Gaopo
authors.initials: G
authors.lastname: Xu
authors.forename: Faxiu
authors.initials: F
authors.lastname: Lan
authors.forename: Shihua
authors.initials: S
authors.lastname: Wang
mesh_terms: D000348:Aflatoxins / Q000096:biosynthesis*; D001231:Aspergillus flavus / Q000187:drug effects / Q000378:metabolism*; D001374:Azacitidine / Q000494:pharmacology*; D019175:DNA Methylation / Q000187:drug effects*; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D004271:DNA, Fungal / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044127:Epigenesis, Genetic; D015966:Gene Expression Regulation, Fungal; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000348:Aflatoxins; D004271:DNA, Fungal; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D015254:DNA Modification Methylases; D001374:Azacitidine
keywords: 5-azacytidine; DNA methylation inhibitor; aflatoxin