Quantitative Characterization of Gene Regulatory Circuits Associated With Fungal Secondary Metabolism to Discover Novel Natural Products
Abstract Microbial genetic circuits are vital for regulating gene expression and synthesizing bioactive compounds. However, assessing their strength and timing, especially in multicellular fungi, remains challenging. Here, an advanced microfluidic platform is combined with a mathematical model enabl...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-12-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202407195 |
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| author | Xinran Xu Yanhong Sun Anxin Zhang Sijia Li Shu Zhang Sijing Chen Chunbo Lou Lei Cai Yihua Chen Chunxiong Luo Wen‐Bing Yin |
| author_facet | Xinran Xu Yanhong Sun Anxin Zhang Sijia Li Shu Zhang Sijing Chen Chunbo Lou Lei Cai Yihua Chen Chunxiong Luo Wen‐Bing Yin |
| author_sort | Xinran Xu |
| collection | DOAJ |
| description | Abstract Microbial genetic circuits are vital for regulating gene expression and synthesizing bioactive compounds. However, assessing their strength and timing, especially in multicellular fungi, remains challenging. Here, an advanced microfluidic platform is combined with a mathematical model enabling precise characterization of fungal gene regulatory circuits (GRCs) at the single‐cell level. Utilizing this platform, the expression intensity and timing of 30 transcription factor‐promoter combinations derived from two representative fungal GRCs, using the model fungus Aspergillus nidulans are determined. As a proof of concept, the selected GRC combination is utilized to successfully refactor the biosynthetic pathways of bioactive molecules, precisely control their production, and activate the expression of the silenced biosynthetic gene clusters (BGCs). This study provides insights into microbial gene regulation and highlights the potential of platform in fungal synthetic biology applications and the discovery of novel natural products. |
| format | Article |
| id | doaj-art-355fe391d1504a5fb2fcda41f8f2601a |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-355fe391d1504a5fb2fcda41f8f2601a2024-12-18T14:18:10ZengWileyAdvanced Science2198-38442024-12-011147n/an/a10.1002/advs.202407195Quantitative Characterization of Gene Regulatory Circuits Associated With Fungal Secondary Metabolism to Discover Novel Natural ProductsXinran Xu0Yanhong Sun1Anxin Zhang2Sijia Li3Shu Zhang4Sijing Chen5Chunbo Lou6Lei Cai7Yihua Chen8Chunxiong Luo9Wen‐Bing Yin10State Key Laboratory of Mycology Institute of Microbiology Chinese Academy of Sciences Beijing 100101 P. R. ChinaCenter for Quantitative Biology Academy for Advanced Interdisciplinary Studies Peking University Beijing 100871 P. R. ChinaState Key Laboratory of Mycology Institute of Microbiology Chinese Academy of Sciences Beijing 100101 P. R. ChinaState Key Laboratory of Mycology Institute of Microbiology Chinese Academy of Sciences Beijing 100101 P. R. ChinaState Key Laboratory of Mycology Institute of Microbiology Chinese Academy of Sciences Beijing 100101 P. R. ChinaThe State Key Laboratory for Artificial Microstructures and Mesoscopic Physics School of Physics Peking University Beijing 100871 P. R. ChinaCAS Key Laboratory of Quantitative Engineering Biology Shenzhen Institute of Synthetic Biology Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences Shenzhen 518055 P. R. ChinaState Key Laboratory of Mycology Institute of Microbiology Chinese Academy of Sciences Beijing 100101 P. R. ChinaMedical School University of Chinese Academy of Sciences Beijing 100049 P. R. ChinaCenter for Quantitative Biology Academy for Advanced Interdisciplinary Studies Peking University Beijing 100871 P. R. ChinaState Key Laboratory of Mycology Institute of Microbiology Chinese Academy of Sciences Beijing 100101 P. R. ChinaAbstract Microbial genetic circuits are vital for regulating gene expression and synthesizing bioactive compounds. However, assessing their strength and timing, especially in multicellular fungi, remains challenging. Here, an advanced microfluidic platform is combined with a mathematical model enabling precise characterization of fungal gene regulatory circuits (GRCs) at the single‐cell level. Utilizing this platform, the expression intensity and timing of 30 transcription factor‐promoter combinations derived from two representative fungal GRCs, using the model fungus Aspergillus nidulans are determined. As a proof of concept, the selected GRC combination is utilized to successfully refactor the biosynthetic pathways of bioactive molecules, precisely control their production, and activate the expression of the silenced biosynthetic gene clusters (BGCs). This study provides insights into microbial gene regulation and highlights the potential of platform in fungal synthetic biology applications and the discovery of novel natural products.https://doi.org/10.1002/advs.202407195filamentous fungigene regulatory circuitsmicrofluidicsquantificationsecondary metabolism |
| spellingShingle | Xinran Xu Yanhong Sun Anxin Zhang Sijia Li Shu Zhang Sijing Chen Chunbo Lou Lei Cai Yihua Chen Chunxiong Luo Wen‐Bing Yin Quantitative Characterization of Gene Regulatory Circuits Associated With Fungal Secondary Metabolism to Discover Novel Natural Products Advanced Science filamentous fungi gene regulatory circuits microfluidics quantification secondary metabolism |
| title | Quantitative Characterization of Gene Regulatory Circuits Associated With Fungal Secondary Metabolism to Discover Novel Natural Products |
| title_full | Quantitative Characterization of Gene Regulatory Circuits Associated With Fungal Secondary Metabolism to Discover Novel Natural Products |
| title_fullStr | Quantitative Characterization of Gene Regulatory Circuits Associated With Fungal Secondary Metabolism to Discover Novel Natural Products |
| title_full_unstemmed | Quantitative Characterization of Gene Regulatory Circuits Associated With Fungal Secondary Metabolism to Discover Novel Natural Products |
| title_short | Quantitative Characterization of Gene Regulatory Circuits Associated With Fungal Secondary Metabolism to Discover Novel Natural Products |
| title_sort | quantitative characterization of gene regulatory circuits associated with fungal secondary metabolism to discover novel natural products |
| topic | filamentous fungi gene regulatory circuits microfluidics quantification secondary metabolism |
| url | https://doi.org/10.1002/advs.202407195 |
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