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<p>Many life-saving drugs are derived from fungal secondary metabolites, and the rich diversity of these metabolites is a gold mine of bioactive compounds for drug discovery. However, the biosynthetic genes for most secondary metabolites remain transcriptionally silent in fungi, posing a significant bottleneck in their discovery. Here, we apply a systematic approach to separately over-express 51 secondary metabolism-related transcription factors using the strong inducible promoter of the <i>xylP</i> gene from <i>Penicillium chrysogenum</i>. Growing the individual secondary metabolism transcription factor over-expression strains under inducible conditions leads to the production of a collection of diverse metabolites with anti-bacterial, anti-fungal and anti-cancer activities. The overall approach and the over-expression system established in this study are broadly-applicable, providing a valuable means to revealing the pharmaceutical potentials of fungi.</p>

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Systematic over-expression of secondary metabolism transcription factors to reveal the pharmaceutical potential of Aspergillus nidulans

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月9日

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  • Shuhui Guo,
  • Lakhansing Pardeshi,
  • Longguang Qin,
  • Chris Y. Cheung,
  • Xiaofeng Liu,
  • Lu Fan,
  • Chi Cheng Mok,
  • Chirag Parsania,
  • Zhiqiang Dong,
  • Ben C. B. Ko,
  • Kaeling Tan,
  • Koon Ho Wong

摘要

Many life-saving drugs are derived from fungal secondary metabolites, and the rich diversity of these metabolites is a gold mine of bioactive compounds for drug discovery. However, the biosynthetic genes for most secondary metabolites remain transcriptionally silent in fungi, posing a significant bottleneck in their discovery. Here, we apply a systematic approach to separately over-express 51 secondary metabolism-related transcription factors using the strong inducible promoter of the xylP gene from Penicillium chrysogenum. Growing the individual secondary metabolism transcription factor over-expression strains under inducible conditions leads to the production of a collection of diverse metabolites with anti-bacterial, anti-fungal and anti-cancer activities. The overall approach and the over-expression system established in this study are broadly-applicable, providing a valuable means to revealing the pharmaceutical potentials of fungi.