Dimethylformamide Inhibits Fungal Growth and Aflatoxin B1 Biosynthesis in Aspergillus flavus by Down-Regulating Glucose Metabolism and Amino Acid Biosynthesis.

Lin Pan,Fuguo Xing,Jing Jin,Qingli Yang,Peng Chang

doi:10.3390/toxins12110683

Abstract

Aflatoxins (AFs) are secondary metabolites produced by plant fungal pathogens infecting crops with strong carcinogenic and mutagenic properties. Dimethylformamide (DMF) is an excellent solvent widely used in biology, medicine and other fields. However, the effect and mechanism of DMF as a common organic solvent against fungal growth and AFs production are not clear. Here, we discovered that DMF had obvious inhibitory effect against A. flavus, as well as displayed complete strong capacity to combat AFs production. Hereafter, the inhibition mechanism of DMF act on AFs production was revealed by the transcriptional expression analysis of genes referred to AFs biosynthesis. With 1% DMF treatment, two positive regulatory genes of AFs biosynthetic pathway aflS and aflR were down-regulated, leading to the suppression of the structural genes in AFs cluster like aflW, aflP. These changes may be due to the suppression of VeA and the subsequent up-regulation of FluG. Exposure to DMF caused the damage of cell wall and the dysfunction of mitochondria. In particular, it is worth noting that most amino acid biosynthesis and glucose metabolism pathway were down-regulated by 1% DMF using Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Taken together, these RNA-Seq data strongly suggest that DMF inhibits fungal growth and aflatoxin B1 (AFB1) production by A. flavus via the synergistic interference of glucose metabolism, amino acid biosynthesis and oxidative phosphorylation.

Highlights

Aspergillus flavus as plant-invasive fungal pathogens cause enormous losses in the yield and quality of field crops worldwide [1]
In 1993, AFs were classified as a Class I carcinogens by the International Agency for Research on Cancer (IARC) [5,6]
The objective of this study is to investigate the effect of DMF on A. flavus growth and AFs production, and to determine transcriptomic changes in A. flavus treated with DMF

Summary

Introduction

Aspergillus flavus as plant-invasive fungal pathogens cause enormous losses in the yield and quality of field crops worldwide [1]. Under the suitable environmental conditions, A. flavus is prone to produce a series of strong carcinogenic and mutagenic secondary metabolites aflatoxins (AFs) during the process of infecting food and feed [2]. Among AFs, aflatoxin B1 (AFB1 ) is the most toxic and carcinogenic compound known. In the United States, the Food and Drug Administration (FDA) has set the limiting value at 20 μg/kg for total AFs (B1 , B2 , G1 , G2 ) for all foods, and 100 μg/kg for peanut and corn feed products [9,10]. In the European Union, the European Commission (EC) set the upper limit at 2 μg/kg for AFB1 and 4 μg/kg for total AFs [11]. The appearance of antifungal resistance of chemical fungicides and the safety requirements of practical application in crops globally have incurred the discovery of novel antifungal agents and other antifungal substances [12]

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