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AaLaeA targets AaFla1 to mediate the production of antitumor compound in Alternaria alstroemeria
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  • Can Feng,
  • Wen Zheng,
  • Long Han,
  • Jian Wang,
  • Xing Zha,
  • Qing Xiao,
  • zhangjiang He,
  • Jichuan Kang
Can Feng
Guizhou University
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Wen Zheng
Guizhou University
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Long Han
Guizhou University
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Jian Wang
Guizhou University
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Xing Zha
Guizhou University
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Qing Xiao
Guizhou University
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zhangjiang He
Guizhou University
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Jichuan Kang
Guizhou University

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Abstract

Endophytic fungi are an important source of novel antitumour substances. Previously, we isolated an endophytic fungus, Alternaria alstroemeria, from the medicinal plant Artemisia artemisia, whose crude extracts strongly inhibited A549 tumour cells. We obtained a transformant, namely AaLaeAOE26, which completely loses its antitumour activity due to overexpression of the global regulator AaLaeA. Re-sequencing analysis of the genome revealed that the insertion site was in the non-coding region and did not destroy any other genes. Metabolomics analysis revealed that the level of secondary antitumour metabolic substances was significantly lower in AaLaeAOE26 compared to the wild strain, in particular flavonoids were more downregulated according to the metabolomics analysis. A further comparative transcriptome analysis revealed that a gene encoding FAD -binding domain protein (Fla1) was significantly downregulated. On the other hand, overexpression of AaFla1 led to significant enhancement of antitumor activity against A549 with a 7-fold higher inhibition ratio than the wild strain. At the same time, we also found a significant increase in the accumulation of antitumour metabolites including quercetin, gitogenin, rhodioloside, liensinin, ginsenoside Rg2 and cinobufagin. Our data suggest that the global regulator AaLaeA negatively affects the production of antitumour compounds via controlling the transcription of AaFla1 in endophytic Alternaria alstroemeria.
05 Jun 2023Submitted to Journal of Basic Microbiology
09 Jun 2023Review(s) Completed, Editorial Evaluation Pending
09 Jun 2023Submission Checks Completed
09 Jun 2023Assigned to Editor
11 Jun 2023Reviewer(s) Assigned
13 Jul 2023Editorial Decision: Revise Minor
21 Jul 20231st Revision Received
21 Jul 2023Assigned to Editor
21 Jul 2023Submission Checks Completed
21 Jul 2023Review(s) Completed, Editorial Evaluation Pending
22 Jul 2023Reviewer(s) Assigned
13 Aug 2023Editorial Decision: Revise Minor
26 Aug 20232nd Revision Received
26 Aug 2023Assigned to Editor
26 Aug 2023Submission Checks Completed
26 Aug 2023Review(s) Completed, Editorial Evaluation Pending
27 Aug 2023Reviewer(s) Assigned
06 Sep 2023Editorial Decision: Accept