Lysine Succinylation of VBS Contributes to Sclerotia Development and Aflatoxin Biosynthesis in Aspergillus flavus DOI Creative Commons
Yu Wang, Mingkun Yang, Feng Ge

et al.

Molecular & Cellular Proteomics, Journal Year: 2022, Volume and Issue: 22(2), P. 100490 - 100490

Published: Dec. 22, 2022

Aspergillus flavus is a common saprophytic and pathogenic fungus, its secondary metabolic pathways are one of the most highly characterized owing to aflatoxin (AF) metabolite affecting global economic crops human health. Different natural environments can cause significant variations in AF synthesis. Succinylation was recently identified as critical regulatory post-translational modifications pathways. It primarily reported cells bacteria with few studies on fungi. Proteomic quantification lysine succinylation (Ksuc) exploring potential involvement metabolism regulation (including production) has not been performed under conditions A. flavus. In this study, method based tandem mass tag labeling antibody-based affinity enrichment succinylated peptides via high accuracy nano-liquid chromatography spectrometry explore mechanism pathogenicity naturally isolated strains varying toxin production. Altogether, 1240 Ksuc sites 768 proteins were 1103 685 quantified. Comparing protein levels between low AF-producing strains, bioinformatics analysis indicated that located biosynthetic pathway downregulated, which directly affected Versicolorin B synthase key catalytic enzyme for heterochrome synthesis during Site-directed mutagenesis biochemical revealed versicolorin an important sclerotia development biosynthesis summary, our quantitative study succinylome high/low role regulating biosynthesis. We novel insights into using rich source metabolism-related enzymes regulated by succinylation.

Language: Английский

zol and fai: large-scale targeted detection and evolutionary investigation of gene clusters DOI Creative Commons
Rauf Salamzade, Patricia Q. Tran, Cody Martin

et al.

Nucleic Acids Research, Journal Year: 2025, Volume and Issue: 53(3)

Published: Jan. 24, 2025

Abstract Many universally and conditionally important genes are genomically aggregated within clusters. Here, we introduce fai zol, which together enable large-scale comparative analysis of different types gene clusters mobile-genetic elements, such as biosynthetic (BGCs) or viruses. Fundamentally, they overcome a current bottleneck to reliably perform comprehensive orthology inference at large scale across broad taxonomic contexts thousands genomes. First, allows the identification orthologous instances query cluster interest amongst database target Subsequently, zol enables reliable, context-specific ortholog groups for individual protein-encoding instances. In addition, performs functional annotation computes variety evolutionary statistics each inferred group. Importantly, in comparison tools visual exploration homologous relationships between clusters, can handle produce detailed reports that easy digest. To showcase apply them for: (i) longitudinal tracking virus metagenomes, (ii) performing population genetic investigations BGCs fungal species, (iii) uncovering trends virulence-associated genomes from diverse bacterial genus.

Language: Английский

Citations

2
Developing fungal heterologous expression platforms to explore and improve the production of natural products from fungal biodiversity DOI Creative Commons
Xiangfeng Meng, Yu Fang,

Mingyang Ding

et al.

Biotechnology Advances, Journal Year: 2021, Volume and Issue: 54, P. 107866 - 107866

Published: Nov. 12, 2021

Natural products from fungi represent an important source of biologically active metabolites notably for therapeutic agent development. Genome sequencing revealed that the number biosynthetic gene clusters (BGCs) in is much larger than expected. Unfortunately, most them are silent or barely expressed under laboratory culture conditions. Moreover, many nature uncultivable cannot be genetically manipulated, restricting extraction and identification bioactive these species. Rapid exploration tremendous cryptic fungal BGCs necessitates development heterologous expression platforms, which will facilitate efficient production natural cell factories. Host selection, BGC assembly methods, promoters used expression, metabolic engineering strategies compartmentalization pathways key aspects consideration to develop such a microbial platform. In present review, we summarize current progress on above challenges promote research effort relevant fields.

Language: Английский

Citations

58
Correlative metabologenomics of 110 fungi reveals metabolite–gene cluster pairs DOI
Lindsay K. Caesar,

Fatma Ayaloglu Butun,

Matthew T. Robey

et al.

Nature Chemical Biology, Journal Year: 2023, Volume and Issue: 19(7), P. 846 - 854

Published: March 6, 2023

Language: Английский

Citations

30
Evolutionary investigations of the biosynthetic diversity in the skin microbiome using lsaBGC DOI Creative Commons
Rauf Salamzade, Jonathan Cheong, Shelby Sandstrom

et al.

Microbial Genomics, Journal Year: 2023, Volume and Issue: 9(4)

Published: April 28, 2023

Bacterial secondary metabolites, synthesized by enzymes encoded in biosynthetic gene clusters (BGCs), can underlie microbiome homeostasis and serve as commercialized products, which have historically been mined from a select group of taxa. While evolutionary approaches proven beneficial for prioritizing BGCs experimental characterization efforts to uncover new natural dedicated bioinformatics tools designed comparative analysis within focal taxa are limited. We thus developed l ineage s pecific nalysis ( lsa BGC; https://github.com/Kalan-Lab/lsaBGC ) aid exploration microdiversity trends across homologous groupings BGCs, cluster families (GCFs), any bacterial interest. BGC enables rapid direct identification GCFs genomes, calculates statistics conservation genes, builds framework allow base resolution mining novel variants through metagenomic exploration. Through application the suite four genera commonly found skin microbiomes, we insights into evolution diversity their BGCs. show that virulence-associated carotenoid staphyloxanthin Staphylococcus aureus is ubiquitous genus . one GCF encoding biosynthesis showcases evidence plasmid-mediated horizontal transfer (HGT) between species, another appears be transmitted vertically amongst sub-clade skin-associated Further, latter GCF, well conserved S. , has lost most epidermidis common species on human also regarded commensal. identify thousands single-nucleotide (SNVs) Corynebacterium tuberculostearicum sp. complex, narrow, multi-species clade features prevalent healthy microbiomes. Although SNVs were approximately 10 times likely correspond synonymous changes when located top five percentile sites, identified defied this trend predicted amino acid functionally key enzymatic domains. Ultimately, beyond supporting investigations provides important functionalities discovery or directed modification products.

Language: Английский

Citations

27
Microevolution in the pansecondary metabolome of Aspergillus flavus and its potential macroevolutionary implications for filamentous fungi DOI Open Access
Milton T. Drott, Tomás A. Rush,

Tatum R. Satterlee

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(21)

Published: May 20, 2021

Fungi produce a wealth of pharmacologically bioactive secondary metabolites (SMs) from biosynthetic gene clusters (BGCs). It is common practice for drug discovery efforts to treat species' metabolomes as being well represented by single or small number representative genomes. However, this approach misses the possibility that intraspecific population dynamics, such adaptation environmental conditions local microbiomes, may harbor novel BGCs contribute overall niche breadth species. Using 94 isolates Aspergillus flavus, cosmopolitan model fungus, sampled seven states in United States, we dereplicate 7,821 into 92 unique BGCs. We find more than 25% pangenomic show population-specific patterns presence/absence protein divergence. Population-specific make up most accessory-genome BGCs, suggesting different ecological forces maintain accessory genomes be partially mediated differences metabolism. use ultra-high-performance high-resolution mass spectrometry confirm these genetic also result chemotypic SM production populations, which could mediate interactions and acted on selection. Thus, our results suggest paradigm shift previously unrealized population-level reservoirs diversity significant evolutionary, ecological, pharmacological importance. Last, several A. flavus are present parasiticus minisclerotigenes discuss how microevolutionary uncover inform macroevolutionary inferences help align fungal metabolism with existing evolutionary theory.

Language: Английский

Citations

49
The confluence of big data and evolutionary genome mining for the discovery of natural products DOI
Marc G. Chevrette,

Athina Gavrilidou,

Shrikant Mantri

et al.

Natural Product Reports, Journal Year: 2021, Volume and Issue: 38(11), P. 2024 - 2040

Published: Jan. 1, 2021

The development and application of evolutionary genome mining tools databases has propelled natural products research into the modern age Big Data.

Language: Английский

Citations

43
Post‐translational modifications drive secondary metabolite biosynthesis in Aspergillus: a review DOI
Kunlong Yang, Jun Tian, Nancy P. Keller

et al.

Environmental Microbiology, Journal Year: 2022, Volume and Issue: 24(7), P. 2857 - 2881

Published: May 30, 2022

Summary Post‐translational modifications (PTMs) are important for protein function and regulate multiple cellular processes secondary metabolites (SMs) in fungi. Aspergillus species belong to a genus renown an abundance of bioactive metabolites, many as toxins, pharmaceuticals industrial production. The genes required typically co‐localized biosynthetic gene clusters (BGCs), which often localize heterochromatic regions genome ‘turned off’ under laboratory condition. Efforts have been made ‘turn on’ these BGCs by genetic manipulation histone modifications, could convert the structure euchromatin. Additionally, non‐histone PTMs also play critical roles regulation metabolism. In this review, we collate known epigenetic on SM We summarize proteomics approaches bioinformatics tools PTM identification prediction provide future perspectives emerging biosynthesis other

Language: Английский

Citations

36
Triumphs and Challenges of Natural Product Discovery in the Postgenomic Era DOI
Carolina Cano‐Prieto, Agustina Undabarrena, Ana Calheiros de Carvalho

et al.

Annual Review of Biochemistry, Journal Year: 2024, Volume and Issue: 93(1), P. 411 - 445

Published: Aug. 2, 2024

Natural products have played significant roles as medicine and food throughout human history. Here, we first provide a brief historical overview of natural products, their classification biosynthetic origins, the microbiological genetic methods used for discovery. We also describe discuss technologies that revolutionized field, which transitioned from classic genetics to genome-centric discovery approximately two decades ago. then highlight most recent advancements approaches in current postgenomic era, genome mining is standard operation high-throughput analytical allow parallel genes molecules at an unprecedented pace. Finally, new challenges faced by field future systematic heterologous expression strain-independent discovery, promises deliver more vials than ever before.

Language: Английский

Citations

8
Aspergillus flavus pangenome (AflaPan) uncovers novel aflatoxin and secondary metabolite associated gene clusters DOI Creative Commons
Sunil S. Gangurde, Walid Korani, Prasad Bajaj

et al.

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

Citations

6
Ecological generalism drives hyperdiversity of secondary metabolite gene clusters in xylarialean endophytes DOI
Mario Emilio Ernesto Franco, Jennifer H. Wisecaver, A. Elizabeth Arnold

et al.

New Phytologist, Journal Year: 2021, Volume and Issue: 233(3), P. 1317 - 1330

Published: Nov. 19, 2021

Although secondary metabolites are typically associated with competitive or pathogenic interactions, the high bioactivity of endophytic fungi in Xylariales, coupled their abundance and broad host ranges spanning all lineages land plants lichens, suggests that enhanced metabolism might facilitate symbioses phylogenetically diverse hosts. Here, we examined metabolite gene clusters (SMGCs) across 96 Xylariales genomes two clades (Xylariaceae s.l. Hypoxylaceae), including 88 newly sequenced endophytes closely related saprotrophs pathogens. We paired genomic data extensive metadata on endophyte hosts substrates, enabling us to examine factors breadth symbiotic interactions ecological roles. All contain hyperabundant SMGCs; however, Xylariaceae have increased numbers duplications, horizontal transfers (HGTs) SMGCs. Enhanced metabolic diversity is a greater capacity for lignocellulose decomposition. Our results suggest that, as substrate generalists, experience selection diversify SMGCs compared more ecologically specialised Hypoxylaceae species. Overall, our provide new evidence may symbiosis hosts, highlighting importance microbial drive fungal diversity.

Language: Английский

Citations

35