Engineering of Global Transcriptional Regulators (GTRs) in <i>Aspergillus</i> for Natural Product Discovery

The <i>Aspergillus</i> genus is an important group of filamentous fungi, and the various biological activities of its secondary metabolites (SMs) have great biosynthetic potential. Despite over 4200 SMs having been isolated from <i>Aspergillus</i> spp., their metabolic potent...

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Main Authors: Yujie Zhao, Qing Gong, Huawei Zhang
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Journal of Fungi
Subjects:
Online Access:https://www.mdpi.com/2309-608X/11/6/449
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author Yujie Zhao
Qing Gong
Huawei Zhang
author_facet Yujie Zhao
Qing Gong
Huawei Zhang
author_sort Yujie Zhao
collection DOAJ
description The <i>Aspergillus</i> genus is an important group of filamentous fungi, and the various biological activities of its secondary metabolites (SMs) have great biosynthetic potential. Despite over 4200 SMs having been isolated from <i>Aspergillus</i> spp., their metabolic potential remains unexplored due to the presence of numerous silent biosynthetic gene clusters (BGCs) in their genomes. Fortunately, over the last two decades, the global transcriptional regulator (GTR) engineering strategy has emerged as a powerful tool for activating these cryptic BGCs in order to synthesize previously undiscovered SMs from <i>Aspergillus</i> spp. This review highlights recent advances in fungal GTR engineering techniques, the regulatory mechanisms of GTRs, and current challenges and future perspectives for their application in natural product discovery in the genus <i>Aspergillus</i>.
format Article
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issn 2309-608X
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publisher MDPI AG
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series Journal of Fungi
spelling doaj-art-909cd60b128c4dada750f9adca574c4e2025-08-20T02:21:03ZengMDPI AGJournal of Fungi2309-608X2025-06-0111644910.3390/jof11060449Engineering of Global Transcriptional Regulators (GTRs) in <i>Aspergillus</i> for Natural Product DiscoveryYujie Zhao0Qing Gong1Huawei Zhang2School of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, ChinaSchool of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, ChinaSchool of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, ChinaThe <i>Aspergillus</i> genus is an important group of filamentous fungi, and the various biological activities of its secondary metabolites (SMs) have great biosynthetic potential. Despite over 4200 SMs having been isolated from <i>Aspergillus</i> spp., their metabolic potential remains unexplored due to the presence of numerous silent biosynthetic gene clusters (BGCs) in their genomes. Fortunately, over the last two decades, the global transcriptional regulator (GTR) engineering strategy has emerged as a powerful tool for activating these cryptic BGCs in order to synthesize previously undiscovered SMs from <i>Aspergillus</i> spp. This review highlights recent advances in fungal GTR engineering techniques, the regulatory mechanisms of GTRs, and current challenges and future perspectives for their application in natural product discovery in the genus <i>Aspergillus</i>.https://www.mdpi.com/2309-608X/11/6/449global transcriptional regulatorssecondary metabolitesregulatory mechanismsCRISPR/Cas9homologous recombination
spellingShingle Yujie Zhao
Qing Gong
Huawei Zhang
Engineering of Global Transcriptional Regulators (GTRs) in <i>Aspergillus</i> for Natural Product Discovery
Journal of Fungi
global transcriptional regulators
secondary metabolites
regulatory mechanisms
CRISPR/Cas9
homologous recombination
title Engineering of Global Transcriptional Regulators (GTRs) in <i>Aspergillus</i> for Natural Product Discovery
title_full Engineering of Global Transcriptional Regulators (GTRs) in <i>Aspergillus</i> for Natural Product Discovery
title_fullStr Engineering of Global Transcriptional Regulators (GTRs) in <i>Aspergillus</i> for Natural Product Discovery
title_full_unstemmed Engineering of Global Transcriptional Regulators (GTRs) in <i>Aspergillus</i> for Natural Product Discovery
title_short Engineering of Global Transcriptional Regulators (GTRs) in <i>Aspergillus</i> for Natural Product Discovery
title_sort engineering of global transcriptional regulators gtrs in i aspergillus i for natural product discovery
topic global transcriptional regulators
secondary metabolites
regulatory mechanisms
CRISPR/Cas9
homologous recombination
url https://www.mdpi.com/2309-608X/11/6/449
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AT qinggong engineeringofglobaltranscriptionalregulatorsgtrsiniaspergillusifornaturalproductdiscovery
AT huaweizhang engineeringofglobaltranscriptionalregulatorsgtrsiniaspergillusifornaturalproductdiscovery