Quantitative Characterization of Gene Regulatory Circuits Associated With Fungal Secondary Metabolism to Discover Novel Natural Products.

Publisher: WILEY-VCH Country of Publication: Germany NLM ID: 101664569 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2198-3844 (Electronic) Linking ISSN: 21983844 NLM ISO Abbreviation: Adv Sci (Weinh) Subsets: MEDLINE

Original Publication: Weinheim : WILEY-VCH, [2014]-

Aspergillus nidulans*/genetics ; Aspergillus nidulans*/metabolism ; Gene Regulatory Networks*/genetics ; Secondary Metabolism*/genetics ; Biological Products*/metabolism ; Gene Expression Regulation, Fungal*/genetics; Synthetic Biology/methods ; Transcription Factors/metabolism ; Transcription Factors/genetics ; Biosynthetic Pathways/genetics ; Models, Theoretical ; Multigene Family

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.
(© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

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32170066 National Natural Science Foundation of China; 32201197 National Natural Science Foundation of China; 12374203 National Natural Science Foundation of China; KFJ-BRP-009-005 Biological Resources Program and Strategic Priority Research Program, Chinese Academy of Sciences; XDB0830000 Biological Resources Program and Strategic Priority Research Program, Chinese Academy of Sciences; YSBR-111 Chinese Academy of Sciences Project for Young Scientists in Basic Research; ZDBS-LY-SM016 Key Research Program of Frontier Science, Chinese Academy of Sciences

Keywords: filamentous fungi; gene regulatory circuits; microfluidics; quantification; secondary metabolism

0 (Biological Products)
0 (Transcription Factors)

Date Created: 20241028 Date Completed: 20241218 Latest Revision: 20250104

20250114

PMC11653720

10.1002/advs.202407195

39467708