Mining for a new class of fungal natural products: the evolution, diversity, and distribution of isocyanide synthase biosynthetic gene clusters

Nucleic Acids Research, Journal Year: 2023, Volume and Issue: 51(14), P. 7220 - 7235

Published: July 7, 2023

The products of non-canonical isocyanide synthase (ICS) biosynthetic gene clusters (BGCs) mediate pathogenesis, microbial competition, and metal-homeostasis through metal-associated chemistry. We sought to enable research into this class compounds by characterizing the potential evolutionary history these BGCs across Fungal Kingdom. amalgamated a pipeline tools predict based on shared promoter motifs located 3800 ICS in 3300 genomes, making fifth largest specialized metabolites compared canonical classes found antiSMASH. are not evenly distributed fungi, with evidence gene-family expansions several Ascomycete families. show that dit1/2 cluster family (GCF), which was prior only studied yeast, is present ∼30% all Ascomycetes. dit variety exhibits greater similarity bacterial than other fungal ICS, suggesting convergence backbone domain. origins GCF Ascomycota ancient genes diversifying some lineages. Our results create roadmap for future BGCs. developed website (https://isocyanides.fungi.wisc.edu/) facilitates exploration downloading identified GCFs.

Language: Английский

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Aspergillus flavus pangenome (AflaPan) uncovers novel aflatoxin and secondary metabolite associated gene clusters

BMC Plant Biology, Journal Year: 2024, Volume and Issue: 24(1)

Published: May 1, 2024

Abstract Background Aspergillus flavus is an important agricultural and food safety threat due to its production of carcinogenic aflatoxins. It has high level genetic diversity that adapted various environments. Recently, we reported two reference genomes A. isolates, AF13 ( MAT1-2 highly aflatoxigenic isolate) NRRL3357 MAT1-1 moderate aflatoxin producer). Where, insertion 310 kb in included producing gene bZIP transcription factor, named atfC . Observations significant genomic variants between these isolates contrasting phenotypes prompted investigation into variation among other with the goal discovering novel genes potentially associated regulation. Present study was designed three main objectives: (1) collection large number from diverse sources including maize plants field soils; (2) whole genome sequencing collected development a pangenome; (3) pangenome-wide association (Pan-GWAS) identify secondary metabolite cluster genes. Results Pangenome analysis 346 identified total 17,855 unique orthologous clusters, mere 41% (7,315) core 59% (10,540) accessory indicating accumulation during domestication. 5,994 clusters not annotated either or genomes. Pan-genome wide variations 391 pan-genes production. Interestingly, most significantly (94%; 369 associations) belonged expansion resulted incorporation new metabolites. Conclusion In summary, this provides complete pangenome framework for species along pathogen survival The indicated , however AflaPan closed represents optimum Most importantly, newly will be source seeking mitigation strategies needs attention research.

Language: Английский

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A Timeline of Biosynthetic Gene Cluster Discovery in Aspergillus fumigatus: From Characterization to Future Perspectives

Journal of Fungi, Journal Year: 2024, Volume and Issue: 10(4), P. 266 - 266

Published: April 2, 2024

In 1999, the first biosynthetic gene cluster (BGC), synthesizing virulence factor DHN melanin, was characterized in Aspergillus fumigatus. Since then, 19 additional BGCs have been linked to specific secondary metabolites (SMs) this species. Here, we provide a comprehensive timeline of A. fumigatus BGC discovery and find that initial advances centered around commonly expressed SMs where chemical structure informed rationale identification producing (e.g., gliotoxin, fumigaclavine, fumitremorgin, pseurotin A, helvolic acid, fumiquinazoline). Further followed transcriptional profiling ΔlaeA mutant, which aided endocrocin, fumagillin, hexadehydroastechrome, trypacidin, fumisoquin BGCs. These their precursors are produced most studies. Characterization other BGC/SM pairs required efforts, such as induction treatments, including co-culture with bacteria (fumicycline/neosartoricin, fumigermin) or growth under copper starvation (fumivaline, fumicicolin). Finally, four were discovered via overexpression technologies, use heterologous hosts fumihopaside, sphingofungin, sartorypyrone). Initial analysis two studied isolates, Af293 A1160, suggested both harbored ca. 34–36 However, an examination 264 available genomes shows up 20 BGCs, some strains showing considerable variations number composition. new present frontier future metabolism characterization important

Language: Английский

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Biosynthesis of selenium nanoparticles by Aspergillus flavus and Candida albicans for antifungal applications

Micro & Nano Letters, Journal Year: 2021, Volume and Issue: 16(14), P. 656 - 669

Published: Nov. 19, 2021

Abstract Biosynthesis of nanoparticles can replace the available chemical and physical methods by offering new procedures as green syntheses that have proved to be simple, biocompatible, safe, cost‐effective. Recently, antifungal resistance has been reported against different species Aspergillus Candida opportunistic fungi. Selenium (Se‐NPs) were biosynthesized using standard strains A. flavus C. albicans . The presence NPs was confirmed UV‐Vis, FT‐IR, FESEM, EDX, XRD, Zeta potential. Common fungal cultured in Sabouraud dextrose agar medium perform sensitivity test based on minimum inhibitory concentration (MIC) method duplicate. utilization Se‐NPs at concentrations 1, 0.5, 0.25 μg/mL or some even more minor than 0.125 resulted zero growth agents. However, drugs inhibited their 2, 4, 8, 16, 64 itraconazole (ITC). Also, MIC breakpoints for amphotericin B (AMB) anidulafungin (AFG) 2 defining isolates. Based obtained results, biological produced exhibited favourable effects strains.

Language: Английский

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Chromosome assembled and annotated genome sequence of Aspergillus flavus NRRL 3357

G3 Genes Genomes Genetics, Journal Year: 2021, Volume and Issue: 11(8)

Published: June 26, 2021

Aspergillus flavus is an opportunistic pathogen of crops, including peanuts and maize, the second leading cause aspergillosis in immunocompromised patients. A. also a major producer mycotoxin, aflatoxin, potent carcinogen, which results significant crop losses annually. The isolate NRRL 3357 was originally isolated from peanut has been used as model organism for understanding regulation production secondary metabolites, such aflatoxin. A draft genome previously constructed, enabling development molecular tools population biology this particular species. Here, we describe updated, near complete, telomere-to-telomere assembly re-annotation eight chromosomes genome, accomplished via long-read PacBio Oxford Nanopore technologies combined with Illumina short-read sequencing. total 13,715 protein-coding genes were predicted. Using RNA-seq data, improvement achieved predicted 5' 3' untranslated regions, incorporated into new gene models.

Language: Английский

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Genomic and Phenotypic Trait Variation of the Opportunistic Human Pathogen Aspergillus flavus and Its Close Relatives

Microbiology Spectrum, Journal Year: 2022, Volume and Issue: 10(6)

Published: Nov. 1, 2022

Fungal diseases affect millions of humans annually, yet fungal pathogens remain understudied. The mold Aspergillus flavus can cause both aspergillosis and keratitis infections, but closely related species are not considered clinically relevant. To study the evolution A. pathogenicity, we examined genomic phenotypic traits two strains three species, arachidicola (two strains), parasiticus nomiae (one strain). We identified >3,000 orthologous proteins unique to flavus, including seven biosynthetic gene clusters present in absent nonpathogens. characterized secondary metabolite production for all under relevant conditions, temperature salt concentration. Temperature impacted whereas salinity did any species. Strains same produced different metabolites. Growth stress conditions revealed additional heterogeneity within Using invertebrate disease model Galleria mellonella, found virulence varied widely; were more virulent than In a murine keratitis, observed significantly lower severity corneal thickness compared other at 48 h postinfection, 72 h. Our work identifies variations key phenotypic, chemical, attributes between its nonpathogenic relatives reveals extensive strain that does correspond currently established clinical relevance these

Language: Английский

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Insight into the role of niche concept in deciphering the ecological drivers of MPs-associated bacterial communities in mangrove forest

Water Research, Journal Year: 2023, Volume and Issue: 249, P. 120995 - 120995

Published: Dec. 8, 2023

Language: Английский

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The Development of Aspergillus flavus and Biosynthesis of Aflatoxin B1 are Regulated by the Golgi-Localized Mn²⁺ Transporter Pmr1

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(2), P. 1276 - 1291

Published: Jan. 5, 2024

Microorganisms rely on diverse ion transport and trace elements to sustain growth, development, secondary metabolism. Manganese (Mn2+) is essential for various biological processes plays a crucial role in the metabolism of human cells, plants, yeast. In Aspergillus flavus, we confirmed that Pmr1 localized cis- medial-Golgi compartments was critical facilitating Mn2+ transport, fungal metabolism, glycosylation. comparison wild type, Δpmr1 mutant displayed heightened sensitivity environmental stress, accompanied by inhibited synthesis aflatoxin B1, kojic acid, substantial reduction pathogenicity toward peanuts maize. Interestingly, addition exogenous effectively rectified developmental metabolic defects mutant. However, supplement failed restore growth development Δpmr1Δgdt1 double mutant, which indicated Gdt1 compensated functional deficiency pmr1. addition, our results showed pmr1 knockout leads an upregulation O-glycosyl-N-acetylglucose (O-GlcNAc) O-GlcNAc transferase (OGT), while supplementation can glycosylation A. flavus. Collectively, this study indicates regulates via Golgi maintains functions flavus through regulation

Language: Английский

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An environmental isolate of Pseudomonas, 20EI1, reduces Aspergillus flavus growth in an iron-dependent manner and alters secondary metabolism

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 20, 2025

Introduction Aspergillus flavus is an opportunistic pathogenic fungus that infects oilseed crops worldwide. When colonizing plants, it produces mycotoxins, including carcinogenic compounds such as aflatoxins. Mycotoxin contamination results in important economic and health impact. The design of new strategies to control A. colonization mycotoxin paramount. Methods biocontrol potential a promising isolate Pseudomonas spp., 20EI1 against was assessed using bioassays microscopy. To further elucidate the nature this bacterial-fungal interaction, we also performed chemical transcriptomics analyses. Results In present study, able reduce growth . Furthermore, determined inhibition iron-dependent. addition, reduced or blocked production aflatoxin, well cyclopiazonic acid kojic acid. Expression iron-related genes altered presence bacteria involved aflatoxin were down-regulated. Iron supplementation partially reestablished their expression. other secondary metabolite (SM) by bacteria, clusters acid, imizoquin biosynthesis, while cluster corresponding aspergillicin, siderophore, upregulated. Interestingly, global SM regulatory gene mtfA significantly upregulated 20EI1, which could have contributed observed alterations SM. Discussion Our suggest , provide insight into iron-dependent interaction affecting expression numerous genes, among them those

Language: Английский

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Comparative Genomics of Aspergillus Oryzae and Aspergillus Flavus Originated from a Korean Fermentation Starter, Nuruk

Published: Jan. 1, 2025

Language: Английский

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