Effects of nitrogen metabolism on growth and aflatoxin biosynthesis in Aspergillus flavus

J Hazard Mater. 2017 Feb 15;324(Pt B):691-700. doi: 10.1016/j.jhazmat.2016.11.043. Epub 2016 Nov 21.

Abstract

Aflatoxins (AFs), produced mainly by Aspergillus flavus and Aspergillus parasiticus, are strongly toxic and carcinogenic. Here, we showed that glutamine is the optimal nitrogen source for AF-production in A. flavus grown in Czapek Dox medium. Additionally, 4mM glutamine was the threshold for high production of aflatoxin B1. However, no significant impact of glutamine synthetase inhibitor was detected for on AF biosynthesis. In contrast, rapamycin could significantly suppress the glutamine inducing effect on AFs production, simultaneously inhibiting the fungal growth and conidiation. To identify the genes and regulatory networks involved in AFs biosynthesis, especially concerning the nitrogen source metabolism pathway and the target of rapamycin (TOR) signaling pathway, we obtained transcriptomes for A. flavus under treatment of three nitrogen sources by RNA-sequencing. We identified 1429 differentially expressed genes. Through GO and KEGG pathway analyses, the relationship between nitrogen metabolism and AFs biosynthesis was revealed, and the effects of TOR inhibitor were confirmed. Additionally, the quantitative real-time PCR results verified the credibility and reliability of the RNA-seq data, and were consistent with the other experimental results. Our research laid the foundation for a primary study on the involvement of the nitrogen regulatory network and TOR signaling pathway in AF biosynthesis.

Keywords: Aflatoxins; Aspergillus flavus; Glutamine; Nitrogen sources; RNA-seq.

MeSH terms

  • Aflatoxin B1 / biosynthesis*
  • Aspergillus flavus / drug effects
  • Aspergillus flavus / genetics
  • Aspergillus flavus / growth & development*
  • Aspergillus flavus / metabolism
  • Gene Expression Profiling
  • Gene Regulatory Networks / drug effects
  • Glutamate-Ammonia Ligase / antagonists & inhibitors
  • Glutamate-Ammonia Ligase / genetics
  • Glutamine / metabolism*
  • Nitrogen / metabolism*
  • Signal Transduction
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases / metabolism
  • Transcriptome / drug effects

Substances

  • Glutamine
  • Aflatoxin B1
  • TOR Serine-Threonine Kinases
  • Glutamate-Ammonia Ligase
  • Nitrogen
  • Sirolimus