The chemical profile of activated secondary metabolites by overexpressing LaeA in Aspergillus niger

Bin Wang, Xuejie Li, Jioji Tabudravu, Shan Wang, Hai Deng* (Corresponding Author), Li Pan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Although the mechanisms of regulating secondary metabolism by LaeA remains unclear, the synthesis of many secondary metabolites (SMs) in Aspergilli could be activated by LaeA mutation. In our previous sutdy, RNA-seq data has showed that the transcriptional level of many SM backbone genes could be upregulated by overexpressing LaeA. Herein, we analyzed the chemical profile of activated secondary metabolites in the variant of A. niger FGSC A1279 by overexpressing LaeA (OElaeA). 14 compounds were activated in A. niger FGSC A1279 OElaeA variant in the WATM medium. Chemical workup of organic extracts of the culture broth from the A. niger OElaeA mutant identified three pure compounds, flaviolin, orlandin and kotanin. The structures of these compounds were confirmed by HR-ESIMS, 1D/2D NMR, and computer assisted structure elucidation (CASE). Based on homologous alignment and comparison of literatures, the biosynthetic gene cluster (fla) of flaviolin was identified. The in vivo function of the backbone gene, flaA, encoding a multidomain non-reducing polyketide synthase (SAT-KS-AT-PT-ACP), was verified via gene knockout and chemical analysis. Finally, a biosynthetic model for fungal flaviolin was proposed.

Original languageEnglish
Article number126735
Number of pages6
JournalMicrobiological Research
Volume248
Early online date3 Mar 2021
DOIs
Publication statusPublished - 1 Jul 2021

Keywords

  • LaeA factor
  • Secondary metabolites
  • A. niger
  • Flaviolin biosynthetic pathway

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