Transcription Factor Repurposing Offers Insights into Evolution of Biosynthetic Gene Cluster Regulation

Wang, Wenjie; Drott, Milton T.; Greco, Claudio; Luciano-Rosario, Dianiris; Wang, Pin-Mei; Keller, Nancy P.

doi:10.1128/mbio.01399-21

Cited by 18 publications

(20 citation statements)

References 78 publications

(110 reference statements)

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“…The PSTF HmgR is a transcriptional activator for the genes of the tyrosine degradation cluster, which is a different pathway from DHN-melanin and produces an alternative melanin, pyomelanin [93]. 6 in reference [95]. PSTF = pathway specific transcription factor, BGC = biosynthetic gene cluster.…”

Section: Role and Evolution Of Pathway Specific Transcription Factor (Pstf)mentioning

confidence: 99%

“…A highly conserved xan cluster with a xanC homolog (PexanC) was identified in Penicillium expansum. Surprisingly, instead of regulating the Pexan BGC (with the exception of one gene, PexanG), PeXanC activates the citrinin PSTF gene ctnA and increases the production of citrinin [95] (Figure 1e). This divergence is partially explained by the finding that AfXanC and PeXanC recognize different DNA binding sites [95].…”

Section: Pstf With Function Change: Xancmentioning

confidence: 99%

“…Surprisingly, instead of regulating the Pexan BGC (with the exception of one gene, PexanG), PeXanC activates the citrinin PSTF gene ctnA and increases the production of citrinin [95] (Figure 1e). This divergence is partially explained by the finding that AfXanC and PeXanC recognize different DNA binding sites [95]. This gives an example of evolutionary variance and functional change of PSTF homologs.…”

Section: Pstf With Function Change: Xancmentioning

confidence: 99%

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Presence, Mode of Action, and Application of Pathway Specific Transcription Factors in Aspergillus Biosynthetic Gene Clusters

Wang

Keller

et al. 2021

IJMS

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Fungal secondary metabolites are renowned toxins as well as valuable sources of antibiotics, cholesterol-lowering drugs, and immunosuppressants; hence, great efforts were levied to understand how these compounds are genetically regulated. The genes encoding for the enzymes required for synthesizing secondary metabolites are arranged in biosynthetic gene clusters (BGCs). Often, BGCs contain a pathway specific transcription factor (PSTF), a valuable tool in shutting down or turning up production of the BGC product. In this review, we present an in-depth view of PSTFs by examining over 40 characterized BGCs in the well-studied fungal species Aspergillus nidulans and Aspergillus fumigatus. Herein, we find BGC size is a predictor for presence of PSTFs, consider the number and the relative location of PSTF in regard to the cluster(s) regulated, discuss the function and the evolution of PSTFs, and present application strategies for pathway specific activation of cryptic BGCs.

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Section: Role and Evolution Of Pathway Specific Transcription Factor (Pstf)mentioning

confidence: 99%

Section: Pstf With Function Change: Xancmentioning

confidence: 99%

Section: Pstf With Function Change: Xancmentioning

confidence: 99%

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Presence, Mode of Action, and Application of Pathway Specific Transcription Factors in Aspergillus Biosynthetic Gene Clusters

Wang

Keller

et al. 2021

IJMS

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“…After transformation, DNA must be extracted from all transformants for confirmation of successful DNA construct insertion (Basic Protocol 4). Verification of the transformation typically involves PCR screening, Southern blot analysis, or sequencing (Stroe et al, 2020;Southern, 2006;Wang, Drott, et al, 2021).…”

Section: Transformation Of Aspergillus Sppmentioning

confidence: 99%

“…Months can be spent trying various media, temperatures, plating methods, and so on. When trying to genetically activate BGC expression, internal transcription factors may not always regulate the BGC adjacent to it (Wang, Drott, et al., 2021). Additionally, attempts to heterologously express entire clusters in model organisms are not always fruitful.…”

Section: Commentarymentioning

confidence: 99%

Comprehensive Guide to Extracting and Expressing Fungal Secondary Metabolites with Aspergillus fumigatus as a Case Study

et al. 2021

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Fungal secondary metabolites (SMs) have captured the interest of natural products researchers in academia and industry for decades. In recent years, the high rediscovery rate of previously characterized metabolites is making it increasingly difficult to uncover novel compounds. Additionally, the vast majority of fungal SMs reside in genetically intractable fungi or are silent under normal laboratory conditions in genetically tractable fungi. The fungal natural products community has broadly overcome these barriers by altering the physical growth conditions of the fungus and heterologous/homologous expression of biosynthetic gene cluster regulators or proteins. The protocols described here summarize vital methodologies needed when researching SM production in fungi. We also summarize the growth conditions, genetic backgrounds, and extraction protocols for every published SM in Aspergillus fumigatus, enabling readers to easily replicate the production of previously characterized SMs. Readers will also be equipped with the tools for developing their own strategy for expressing and extracting SMs from their given fungus or a suitable heterologous model system.

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Biosynthetic gene cluster synteny: Orthologous polyketide synthases in Hypogymnia physodes, Hypogymnia tubulosa, and Parmelia sulcata

Ahmad,

Ritz,

Calchera

et al. 2023

MicrobiologyOpen

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Lichens are symbiotic associations consisting of a photobiont (algae or cyanobacteria) and a mycobiont (fungus), which together generate a variety of unique secondary metabolites. To access this biosynthetic potential for biotechnological applications, deeper insights into the biosynthetic pathways and corresponding gene clusters are necessary. Here, we provide a comparative view of the biosynthetic gene clusters of three lichen mycobionts derived from Hypogymnia physodes, Hypogymnia tubulosa, and Parmelia sulcata. In addition, we present a high‐quality PacBio metagenome of Parmelia sulcata, from which we extracted the mycobiont bin containing 214 biosynthetic gene clusters. Most biosynthetic gene clusters in these genomes were associated with T1PKSs, followed by NRPSs and terpenes. This study focused on biosynthetic gene clusters related to polyketide synthesis. Based on ketosynthase homology, we identified nine highly syntenic clusters present in all three species. Among the four clusters belonging to nonreducing PKSs, two are putatively linked to lichen substances derived from orsellinic acid (orcinol depsides and depsidones, e.g., lecanoric acid, physodic acid, lobaric acid), one to compounds derived from methylated forms of orsellinic acid (beta orcinol depsides, e.g., atranorin), and one to melanins. Five clusters with orthologs in all three species are linked to reducing PKSs. Our study contributes to sorting and dereplicating the vast PKS diversity found in lichenized fungi. High‐quality sequences of biosynthetic gene clusters of these three common species provide a foundation for further exploration into biotechnological applications and the molecular evolution of lichen substances.

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Transcription Factor Repurposing Offers Insights into Evolution of Biosynthetic Gene Cluster Regulation

Cited by 18 publications

References 78 publications

Presence, Mode of Action, and Application of Pathway Specific Transcription Factors in Aspergillus Biosynthetic Gene Clusters

Presence, Mode of Action, and Application of Pathway Specific Transcription Factors in Aspergillus Biosynthetic Gene Clusters

Comprehensive Guide to Extracting and Expressing Fungal Secondary Metabolites with Aspergillus fumigatus as a Case Study

Biosynthetic gene cluster synteny: Orthologous polyketide synthases in Hypogymnia physodes, Hypogymnia tubulosa, and Parmelia sulcata

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