ArticleACS chemical biology2018
Hybrid Transcription Factor Engineering Activates the Silent Secondary Metabolite Gene Cluster for (+)-Asperlin in Aspergillus nidulans.
Article in ACS chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 51 citations in OpenAlex.
- Discovery of a dimeric isopimarane derivative by reexploring a labdane-related diterpenoid biosynthetic gene cluster in Aspergillus nidulans.Microbial cell factories · 2026Article
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- Composite Recycling with Biocatalytic Thermoset Reforming.Journal of the American Chemical Society · 2024Article
- Transcription Factor Engineering inJournal of natural products · 2024Article
- The Tet-on system for controllable gene expression in the rock-inhabiting black fungus Knufia petricola.Extremophiles : life under extreme conditions · 2024Article
- Genome comparisons reveal accessory genes crucial for the evolution of apple Glomerella leaf spot pathogenicity in Colletotrichum fungi.Molecular plant pathology · 2024Article
- A heterologous expression platform inChemical science · 2023Article
- Molecular regulation of fungal secondary metabolism.World journal of microbiology & biotechnology · 2023Review
- Computer-aided, resistance gene-guided genome mining for proteasome and HMG-CoA reductase inhibitors.Journal of industrial microbiology & biotechnology · 2023Article
- Polyketides as Secondary Metabolites from the GenusJournal of fungi (Basel, Switzerland) · 2023Review
- Maleidride biosynthesis - construction of dimeric anhydrides - more than just heads or tails.Natural product reports · 2023Review
- Genomic Analysis of theMycobiology · 2023Article
- Activation of cryptic biosynthetic gene clusters by fungal artificial chromosomes to produce novel secondary metabolites.AIMS microbiology · 2023Article
- How to Completely Squeeze a Fungus-Advanced Genome Mining Tools for Novel Bioactive Substances.Pharmaceutics · 2022Review
- Characterization of a silent azaphilone biosynthesis gene cluster in Aspergillus terreus NIH 2624.Fungal genetics and biology : FG & B · 2022Article
- In silico analyses of maleidride biosynthetic gene clusters.Fungal biology and biotechnology · 2022Article
- Transcriptional Activation of Biosynthetic Gene Clusters in Filamentous Fungi.Frontiers in bioengineering and biotechnology · 2022Review
- Modular Synthetic Biology Toolkit for Filamentous Fungi.ACS synthetic biology · 2021Article
- Presence, Mode of Action, and Application of Pathway Specific Transcription Factors inInternational journal of molecular sciences · 2021Review
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Fungi are a major source of valuable bioactive secondary metabolites (SMs). These compounds are synthesized by enzymes encoded by genes that are clustered in the genome. The vast majority of SM biosynthetic gene clusters are not expressed under normal growth conditions, and their products are unknown. Developing methods for activation of these silent gene clusters offers the potential for discovering many valuable new fungal SMs. While a number of useful approaches have been developed, they each have limitations, and additional tools are needed. One approach, upregulation of SM gene cluster-specific transcription factors that are associated with many SM gene clusters, has worked extremely well in some cases, but it has failed more often than it has succeeded. Taking advantage of transcription factor domain modularity, we developed a new approach. We fused the DNA-binding domain of a transcription factor associated with a silent SM gene cluster with the activation domain of a robust SM transcription factor, AfoA. Expression of this hybrid transcription factor activated transcription of the genes in the target cluster and production of the antibiotic (+)-asperlin. Deletion of cluster genes confirmed that the cluster is responsible for (+)-asperlin production, and we designate it the aln cluster. Separately, coinduction of expression of two aln cluster genes revealed the pathway intermediate (2 Z,4 Z,6 E)-octa-2,4,6-trienoic acid, a compound with photoprotectant properties. Our findings demonstrate the potential of our novel synthetic hybrid transcription factor strategy to discover the products of other silent fungal SM gene clusters.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.