Chemical repertoire and biosynthetic machinery of the <i>Aspergillus flavus</i> secondary metabolome: A review

Uka, Valdet; Cary, Jeffrey W.; Lebar, Matthew D.; Puel, Olivier; Saeger, Sarah De; Mavungu, José Diana Di

doi:10.1111/1541-4337.12638

Cited by 32 publications

(15 citation statements)

References 313 publications

(528 reference statements)

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“…33 AFB1 is known for its toxigenic effects on the immune system because it could compromise human macrophages and dendritic cells through activating Toll-like receptors, thereby inducing immune-dysregulation. 34,35 Although the association of other fungus from the genus Aspergillus, especially A flavus with cancer, has been frequently reported, 36 here for the first time, we reveal that A rambellii crucially promotes CRC progression. To date, there are very few studies on the association of AFB1 with CRC; hence, further mechanistic investigation is needed to evaluate whether A rambellii produces AFB1 or other aflatoxins to contribute colorectal tumorigenesis.…”

Section: Discussionmentioning

confidence: 48%

Altered Mycobiota Signatures and Enriched Pathogenic Aspergillus rambellii Are Associated With Colorectal Cancer Based on Multicohort Fecal Metagenomic Analyses

et al. 2022

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Section: Discussionmentioning

confidence: 48%

Altered Mycobiota Signatures and Enriched Pathogenic Aspergillus rambellii Are Associated With Colorectal Cancer Based on Multicohort Fecal Metagenomic Analyses

et al. 2022

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“…The annotation of secondary metabolites clusters of A. flavus was obtained from a consolidation between two sources: (1) the SMURF-predicted gene clusters from Giorgianna et al [40] and Ehrlich and Mack [41] and (2) gene clusters which have been experimentally characterized, such as kojic acid, ustiloxin B, asperipin 2a or aspergillic acid [42][43][44][45][46][47] and summarized by Uka et al [48].…”

Section: Expression Analysis Of Secondary Metabolites Clustersmentioning

confidence: 99%

The Solvent Dimethyl Sulfoxide Affects Physiology, Transcriptome and Secondary Metabolism of Aspergillus flavus

Costes

Lippi

Naylies

et al. 2021

JoF

Self Cite

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Dimethyl sulfoxide (DSMO) is a simple molecule widely used because of its great solvating ability, but this solvent also has little-known biological effects, especially on fungi. Aspergillus flavus is a notorious pathogenic fungus which may contaminate a large variety of crops worldwide by producing aflatoxins, endangering at the same time food safety and international trade. The aim of this study was to characterize the effect of DMSO on A. flavus including developmental parameters such as germination and sporulation, as well as its transcriptome profile using high-throughput RNA-sequencing assay and its impact on secondary metabolism (SM). After DMSO exposure, A. flavus displayed depigmented conidia in a dose-dependent manner. The four-day exposition of cultures to two doses of DMSO, chosen on the basis of depigmentation intensity (35 mM “low” and 282 mM “high”), led to no significant impact on fungal growth, germination or sporulation. However, transcriptomic data analysis showed that 4891 genes were differentially regulated in response to DMSO (46% of studied transcripts). A total of 4650 genes were specifically regulated in response to the highest dose of DMSO, while only 19 genes were modulated upon exposure to the lowest dose. Secondary metabolites clusters genes were widely affected by the DMSO, with 91% of clusters impacted at the highest dose. Among these, aflatoxins, cyclopiazonic acid and ustiloxin B clusters were totally under-expressed. The genes belonging to the AFB1 cluster were the most negatively modulated ones, the two doses leading to 63% and 100% inhibition of the AFB1 production, respectively. The SM analysis also showed the disappearance of ustiloxin B and a 10-fold reduction of cyclopiazonic acid level when A. flavus was treated by the higher DMSO dose. In conclusion, the present study showed that DMSO impacted widely A. flavus’ transcriptome, including secondary metabolism gene clusters with the aflatoxins at the head of down-regulated ones. The solvent also inhibits conidial pigmentation, which could illustrate common regulatory mechanisms between aflatoxins and fungal pigment pathways. Because of its effect on major metabolites synthesis, DMSO should not be used as solvent especially in studies testing anti-aflatoxinogenic compounds.

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“…4 C,D). There are 55 predicted (by SMURF software 41 ) SM gene clusters in A. flavus 42 , and at least one non-gene-cluster SM pathway that produces Kojic acid 43 . To decipher how individual SM pathways were affected, we analyzed the expression patterns of key “backbone” enzymes for each SM gene cluster as described in Ref.…”

Section: Resultsmentioning

confidence: 99%

A methanolic extract of Zanthoxylum bungeanum modulates secondary metabolism regulator genes in Aspergillus flavus and shuts down aflatoxin production

Abbas

Wright

El-Sawi

et al. 2022

Sci Rep

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Aflatoxin B1 (AFB1) is a food-borne toxin produced by Aspergillus flavus and a few similar fungi. Natural anti-aflatoxigenic compounds are used as alternatives to chemical fungicides to prevent AFB1 accumulation. We found that a methanolic extract of the food additive Zanthoxylum bungeanum shuts down AFB1 production in A. flavus. A methanol sub-fraction (M20) showed the highest total phenolic/flavonoid content and the most potent antioxidant activity. Mass spectrometry analyses identified four flavonoids in M20: quercetin, epicatechin, kaempferol-3-O-rhamnoside, and hyperoside. The anti-aflatoxigenic potency of M20 (IC50: 2–4 µg/mL) was significantly higher than its anti-proliferation potency (IC50: 1800–1900 µg/mL). RNA-seq data indicated that M20 triggers significant transcriptional changes in 18 of 56 secondary metabolite pathways in A. flavus, including repression of the AFB1 biosynthesis pathway. Expression of aflR, the specific activator of the AFB1 pathway, was not changed by M20 treatment, suggesting that repression of the pathway is mediated by global regulators. Consistent with this, the Velvet complex, a prominent regulator of secondary metabolism and fungal development, was downregulated. Decreased expression of the conidial development regulators brlA and Medusa, genes that orchestrate redox responses, and GPCR/oxylipin-based signal transduction further suggests a broad cellular response to M20. Z. bungeanum extracts may facilitate the development of safe AFB1 control strategies.

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Chemical repertoire and biosynthetic machinery of the Aspergillus flavus secondary metabolome: A review

Cited by 32 publications

References 313 publications

Altered Mycobiota Signatures and Enriched Pathogenic Aspergillus rambellii Are Associated With Colorectal Cancer Based on Multicohort Fecal Metagenomic Analyses

Altered Mycobiota Signatures and Enriched Pathogenic Aspergillus rambellii Are Associated With Colorectal Cancer Based on Multicohort Fecal Metagenomic Analyses

The Solvent Dimethyl Sulfoxide Affects Physiology, Transcriptome and Secondary Metabolism of Aspergillus flavus

A methanolic extract of Zanthoxylum bungeanum modulates secondary metabolism regulator genes in Aspergillus flavus and shuts down aflatoxin production

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