The Molecular Mechanism of Perillaldehyde Inducing Cell Death in Aspergillus flavus by Inhibiting Energy Metabolism Revealed by Transcriptome Sequencing

Int J Mol Sci. 2020 Feb 23;21(4):1518. doi: 10.3390/ijms21041518.


Perillaldehyde (PAE), an essential oil in Perilla plants, serves as a safe flavor ingredient in foods, and shows an effectively antifungal activity. Reactive oxygen species (ROS) accumulation in Aspergillus flavus plays a critical role in initiating a metacaspase-dependent apoptosis. However, the reason for ROS accumulation in A. flavus is not yet clear. Using transcriptome sequencing of A. flavus treated with different concentrations of PAE, our data showed that the ROS accumulation might have been as a result of an inhibition of energy metabolism with less production of reducing power. By means of GO and KEGG enrichment analysis, we screened four key pathways, which were divided into two distinct groups: a downregulated group that was made up of the glycolysis and pentose phosphate pathway, and an upregulated group that consisted of MAPK signaling pathway and GSH metabolism pathway. The inhibition of dehydrogenase gene expression in two glycometabolism pathways might play a crucial role in antifungal mechanism of PAE. Also, in our present study, we systematically showed a gene interaction network of how genes of four subsets are effected by PAE stress on glycometabolism, oxidant damage repair, and cell cycle control. This research may contribute to explaining an intrinsic antifungal mechanism of PAE against A. flavus.

Keywords: Aspergillus flavus; Perilla; antifungal mechanism; energy metabolism; oxidative stress.

MeSH terms

  • Antifungal Agents / pharmacology*
  • Apoptosis / drug effects
  • Aspergillus flavus / drug effects*
  • Aspergillus flavus / genetics
  • Aspergillus flavus / metabolism
  • Cell Death / drug effects*
  • Energy Metabolism / drug effects*
  • Gene Expression Regulation, Fungal / drug effects
  • Glycolysis / drug effects
  • Monoterpenes / metabolism
  • Monoterpenes / pharmacology*
  • Oils, Volatile / pharmacology
  • Oxidative Stress / drug effects
  • Pentose Phosphate Pathway / drug effects
  • Protein Interaction Maps
  • Reactive Oxygen Species / metabolism
  • Transcriptome / drug effects*


  • Antifungal Agents
  • Monoterpenes
  • Oils, Volatile
  • Reactive Oxygen Species
  • perillaldehyde