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

Toxins (Basel). 2020 Oct 29;12(11):683. 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.

Keywords: Aspergillus flavus; aflatoxins; amino acid biosynthesis; dimethylformamide; glucose metabolism; mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aflatoxin B1 / biosynthesis*
  • Amino Acids / biosynthesis
  • Aspergillus flavus / drug effects*
  • Aspergillus flavus / genetics
  • Aspergillus flavus / growth & development
  • Aspergillus flavus / metabolism
  • Dimethylformamide / pharmacology*
  • Down-Regulation
  • Gene Expression Regulation, Fungal / drug effects
  • Glucose / metabolism
  • Oxidative Phosphorylation / drug effects
  • RNA-Seq
  • Solvents / pharmacology*

Substances

  • Amino Acids
  • Solvents
  • Dimethylformamide
  • Aflatoxin B1
  • Glucose