The Small GTPases in Fungal Signaling Conservation and Function DOI Creative Commons
Mitzuko Dautt‐Castro, Maria Montserrat Rosendo‐Vargas, Sergio Casas‐Flores

et al.

Cells, Journal Year: 2021, Volume and Issue: 10(5), P. 1039 - 1039

Published: April 28, 2021

Monomeric GTPases, which belong to the Ras superfamily, are small proteins involved in many biological processes. They fine-tuned regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating (GAPs). Several families have been identified organisms from different kingdoms. Overall, most studied Ras, Rho, Rab, Ran, Arf, Miro. Recently, a new family named Big GTPases was reported. As general rule, of all five characteristic motifs (G1–G5), some specific features for each described. Here, we present an exhaustive analysis these GTPase fungi, using 56 genomes belonging phyla. For this purpose, used distinct approaches such as phylogenetics sequences analysis. The main functions described monomeric fungi include morphogenesis, secondary metabolism, vesicle trafficking, virulence, discussed here. Their participation during fungus–plant interactions is reviewed well.

Language: Английский

Toward a Fully Resolved Fungal Tree of Life DOI
Timothy Y. James, Jason Stajich, Chris Todd Hittinger

et al.

Annual Review of Microbiology, Journal Year: 2020, Volume and Issue: 74(1), P. 291 - 313

Published: July 14, 2020

In this review, we discuss the current status and future challenges for fully elucidating fungal tree of life. last 15 years, advances in genomic technologies have revolutionized systematics, ushering field into phylogenomic era. This has made unthinkable possible, namely access to entire genetic record all known extant taxa. We first review highlight areas where additional effort will be required. then analytical imposed by volume data methods recover most accurate species given sea gene trees. Highly resolved deeply sampled trees are being leveraged novel ways study radiations, delimitation, metabolic evolution. Finally, critical issue incorporating unnamed uncultured dark matter taxa that represent vast majority diversity.

Language: Английский

Citations

212
Fungal–fungal co-culture: a primer for generating chemical diversity DOI Creative Commons
Sonja L. Knowles, Huzefa A. Raja, Christopher D. Roberts

et al.

Natural Product Reports, Journal Year: 2022, Volume and Issue: 39(8), P. 1557 - 1573

Published: Jan. 1, 2022

Covering: 2002 to 2020In their natural environment, fungi must compete for resources. It has been hypothesized that this competition likely induces the biosynthesis of secondary metabolites defence. In a quest discover new chemical diversity from fungal cultures, growing trend recapitulate competitive environment in laboratory, essentially co-culture. This review covers fungal-fungal co-culture studies beginning with first literature report 2002. Since then, there number reported as result studies. Specifically, discusses and provides insights into (1) rationale pairing strains, (2) ways grow co-culture, (3) different approaches screening co-cultures diversity, (4) determining metabolite-producing strain, (5) final thoughts regarding approach. Our goal is provide set practical strategies generate unique products research community can utilize.

Language: Английский

Citations

73
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
Advances and Challenges in CRISPR/Cas-Based Fungal Genome Engineering for Secondary Metabolite Production: A Review DOI Creative Commons
Duoduo Wang,

Shunda Jin,

Qianhui Lu

et al.

Journal of Fungi, Journal Year: 2023, Volume and Issue: 9(3), P. 362 - 362

Published: March 15, 2023

Fungi represent an important source of bioactive secondary metabolites (SMs), which have wide applications in many fields, including medicine, agriculture, human health, and other industries. The genes involved SM biosynthesis are usually clustered adjacent to each into a region known as biosynthetic gene cluster (BGC). recent advent diversity genetic genomic technologies has facilitated the identification cryptic or uncharacterized BGCs their associated SMs. However, there still challenges that hamper broader exploration industrially metabolites. advanced CRISPR/Cas system revolutionized fungal engineering enabled discovery novel compounds. In this review, we firstly introduce relationships with SMs, followed by brief summary conventional strategies for engineering. Next, range state-of-the-art CRISPR/Cas-based tools been developed review these methods fungi research on Finally, limitations systems discussed directions future proposed order expand improve efficiency

Language: Английский

Citations

31
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

28
Key insights into secondary metabolites from various Chaetomium species DOI Open Access
Vagish Dwibedi, Santosh Kumar Rath, Sahil Jain

et al.

Applied Microbiology and Biotechnology, Journal Year: 2023, Volume and Issue: 107(4), P. 1077 - 1093

Published: Jan. 17, 2023

Language: Английский

Citations

24
Copy number variation introduced by a massive mobile element facilitates global thermal adaptation in a fungal wheat pathogen DOI Creative Commons
Sabina Moser Tralamazza, Emile Gluck‐Thaler, Alice Feurtey

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 8, 2024

Abstract Copy number variation (CNV) can drive rapid evolution in changing environments. In microbial pathogens, such adaptation is a key factor underpinning epidemics and colonization of new niches. However, the genomic determinants remain poorly understood. Here, we systematically investigate CNVs large genome sequencing dataset spanning worldwide collection 1104 genomes from major wheat pathogen Zymoseptoria tritici . We found overall strong purifying selection acting on most CNVs. Genomic defense mechanisms likely accelerated gene loss over episodes continental colonization. Local along climatic gradients was facilitated by affecting secondary metabolite production general. One strongest loci for highly conserved NAD-dependent Sirtuin family. The CNV locus localizes to an ~68-kb Starship mobile element unique species carrying genes expressed during plant infection. has lost ability transpose, demonstrating how ongoing domestication cargo-carrying selfish elements contribute selectable within populations. Our work highlights standing copy numbers at global scale be driving metabolic species.

Language: Английский

Citations

11
Predicting fungal secondary metabolite activity from biosynthetic gene cluster data using machine learning DOI Creative Commons
Olivia Riedling, Allison S. Walker, Antonis Rokas

et al.

Microbiology Spectrum, Journal Year: 2024, Volume and Issue: 12(2)

Published: Jan. 9, 2024

Fungal secondary metabolites (SMs) contribute to the diversity of fungal ecological communities, niches, and lifestyles. Many SMs have one or more medically industrially important activities (e.g., antifungal, antibacterial, antitumor). The genes necessary for SM biosynthesis are typically located right next each other in genome known as biosynthetic gene clusters (BGCs). However, whether bioactivity can be predicted from specific attributes BGCs remains an open question. We adapted machine learning models that bacterial BGC data with accuracies high 80% data. trained our predict cytotoxic/antitumor on two sets: (i) (data set comprised 314 BGCs) (ii) (314 (1,003 BGCs). found had balanced between 51% 68%, whereas training 56% 68%. low prediction accuracy bioactivities likely stems small size set; this lack data, coupled finding including did not substantially change currently limits application approaches studies. With >15,000 characterized SMs, millions putative genomes, increased demand novel drugs, efforts systematically link urgently needed.IMPORTANCEFungi key sources natural products iconic penicillin statins. DNA sequencing has revealed there pathways but chemical structures >99% produced by these remain unknown. used artificial intelligence diverse pathways. predictions were generally low, because only very few known. products, present study suggests is urgent need identify pathways, their bioactivities.

Language: Английский

Citations

10
Advances, opportunities, and challenges in methods for interrogating the structure activity relationships of natural products DOI Creative Commons
Christine Mae F. Ancajas, Abiodun S. Oyedele, Caitlin M. Butt

et al.

Natural Product Reports, Journal Year: 2024, Volume and Issue: 41(10), P. 1543 - 1578

Published: Jan. 1, 2024

This review highlights methods for studying structure activity relationships of natural products and proposes that these are complementary could be used to build an iterative computational-experimental workflow.

Language: Английский

Citations

10
Biosynthesis of the Antifungal Polyhydroxy-Polyketide Acrophialocinol DOI Creative Commons

Carsten Wieder,

Moritz Künzer,

Rainer Wiechert

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: 27(4), P. 1036 - 1041

Published: Jan. 22, 2025

Bioactivity-guided isolation identified the main antifungal compounds produced by Acrophialophora levis as new polyhydroxy-polyketides acrophialocinol (1) and acrophialocin (2). Their biosynthesis was elucidated heterologous reconstitution in Aspergillus oryzae involves an α-ketoglutarate-dependent dioxygenase-catalyzed α-hydroxylation, resulting formation of a tertiary alcohol that is indispensable for activity. Furthermore, self-resistance toward mediated conserved RTA1-like protein encoded acr biosynthetic gene cluster.

Language: Английский

Citations

2