Systematic over-expression of secondary metabolism transcription factors to reveal the pharmaceutical potential of Aspergillus nidulans
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.
Authors
- Kaeling Tan (ORCID: https://orcid.org/0000-0002-3347-7628)
- Longguang Qin (ORCID: https://orcid.org/0000-0001-7110-5457)
- Koon Ho Wong (ORCID: https://orcid.org/0000-0002-9264-5118)
- Chi Chiu Mok (ORCID: https://orcid.org/0000-0003-3696-1228)
- Chirag Parsania (ORCID: https://orcid.org/0000-0003-4873-2385)
- Ben C.B. Ko (ORCID: https://orcid.org/0000-0003-2027-5899)
- Shuhui Guo (ORCID: https://orcid.org/0000-0002-3217-5871)
- Chris Cheung (ORCID: https://orcid.org/0000-0003-0840-4117)
- Lakhansing Pardeshi (ORCID: https://orcid.org/0000-0003-0702-5465)
- Fan Lü (ORCID: https://orcid.org/0000-0003-0846-147X)
- Zhiqiang Dong (ORCID: https://orcid.org/0000-0002-3435-0522)
- Xiaofeng Liu
Institutions
- Hong Kong Polytechnic University (HK)
- University of Macau (MO)
- Wuxi Taihu Hospital (CN)
Publication Details
- Journal
- Communications Biology
- Published
- 2025-10-09
- DOI
- https://doi.org/10.1038/s42003-025-08840-z
- Citations
- 1
- Primary Topic
- Microbial Natural Products and Biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 1.39
Funders
- United Mitochondrial Disease Foundation
- Universidade de Macau
- Fundo para o Desenvolvimento das Ciências e da Tecnologia
- Faculdade de Ciências da Saúde, Universidade de Macau