4-Hydroxy-7-methyl-3-phenylcoumarin Suppresses Aflatoxin Biosynthesis via Downregulation of aflK Expressing Versicolorin B Synthase in Aspergillus flavus

Abstract

Naturally occurring coumarins possess antibacterial and antifungal properties. In this study, these natural and synthetic coumarins were used to evaluate their antifungal activities against Aspergillus flavus, which produces aflatoxins. In addition to control antifungal activities, antiaflatoxigenic properties were also determined using a high-performance liquid chromatography in conjunction with fluorescence detection. In this study, 38 compounds tested and 4-hydroxy-7-methyl-3-phenyl coumarin showed potent antifungal and antiaflatoxigenic activities against A. flavus. Inhibitory mode of antiaflatoxigenic action by 4-hydroxy-7-methyl-3-phenyl coumarin was based on the downregulation of aflD, aflK, aflQ, and aflR in aflatoxin biosynthesis. In the cases of coumarins, antifungal and aflatoxigenic activities are highly related to the lack of diene moieties in the structures. In structurally related compounds, 2,3-dihydrobenzofuran exhibited antifungal and antiaflatoxigenic activities against A. flavus. The inhibitory mode of antiaflatoxigenic action by 2,3-dihydrobenzofuran was based on the inhibition of the transcription factor (aflS) in the aflatoxin biosynthesis pathway. These potent inhibitions of 2,3-dihydrobenzofuran and 4-hydroxy-7-methyl-3-phenyl coumarin on the Aspergillus growth and production of aflatoxins contribute to the development of new controlling agents to mitigate aflatoxin contamination.

Docking analysis of hexanoic acid and quercetin with seven domains of polyketide synthase A provided insight into quercetin-mediated aflatoxin biosynthesis inhibition in Aspergillus flavus

“…Kim et al showed the inhibition of aflR by gallic acid in A. flavus (Kim et al 2006). Additionally, 4-hydroxy-7-methyl-3-phenyl coumarin and 2,3-dihydrobenzofuran resulted in downregulation of aflR and aflS in A. flavus, respectively (Moon et al 2017). aflD and aflP are the clustral genes which encode ketoreductase and methyltransferase activities, respectively (Yu 2012).…”

Antifungal and Antiaflatoxigenic Activities of 1,8-Cineole and t-Cinnamaldehyde on Aspergillus flavus

“…Additionally, effective control strategies for fungal infection and toxin production should be organized for the right place and time [19]. Chemical treatment has been seriously considered as an effective method to reduce fungal infection and toxin production in agricultural foods and feedstuffs [9,15,20].…”

Structure, Chemical Analysis, Biosynthesis, Metabolism, Molecular Engineering, and Biological Functions of Phytoalexins

“…These compounds have been the subject of numerous studies over the last two decades. Thirteen research and review articles have been published in this special issue: four articles concern the biosynthesis of phytoalexins as a response to biotic and/or abiotic elicitors capable of inducing their production in plants [ 1 , 2 , 3 , 4 ], two articles describe methods for phytoalexin analysis in complex matrices [ 5 , 6 ], one article reports on phytoalexin metabolism by fungi [ 7 ], and six articles focus on the biological activity of phytoalexins [ 8 , 9 , 10 , 11 , 12 , 13 ].…”

“…Beside their antifungal properties in plants, phytoalexins show preventing activities against human diseases as antioxidant, anticancer, cardioprotective, antibacterial, and antifungal agents. Six articles report here on the biological implication of phytoalexins in human diseases [ 8 , 9 , 10 , 11 , 12 , 13 ].…”

“…In the work of Moon et al [ 8 ], the antifungal activity of natural and synthetic coumarins, which are phenylpropanoid-derivated phytoalexins, was evaluated against Aspergillus flavus . This mold is responsible for the production of various aflatoxins, considered to be the most important carcinogenetic agents of natural origin.…”