Bioinformatic Approaches for Identification of Fungal Species and Detection of Secondary Metabolites

2016 ◽  
pp. 111-134
2019 ◽  
Author(s):  
Andrew S. Urquhart ◽  
Jinyu Hu ◽  
Yit-Heng Chooi ◽  
Alexander Idnurm

AbstractBackgroundViriditoxin is one of the ‘classical’ secondary metabolites produced by fungi and that has antibacterial and other activities; however, the mechanism of its biosynthesis has remained unknown.ResultsHere, a gene cluster responsible for its synthesis was identified, using bioinformatic approaches from two species that produce viriditoxin and then through gene disruption and metabolite profiling. All eight genes in the cluster inPaecilomyces variotiiwere mutated, revealing their roles in the synthesis of this molecule and establishing its biosynthetic pathway which includes an interesting Baeyer-Villiger monooxygenase catalyzed reaction. Additionally, a candidate catalytically-inactive hydrolase was identified as being required for the stereoselective biosynthesis of (M)-viriditoxin. The localization of two proteins were assessed by fusing these proteins to green fluorescent protein, revealing that at least two intracellular structures are involved in the compartmentalization of the synthesis steps of this metabolite.ConclusionsThe full pathway for synthesis of viriditoxin was established by a combination of genomics, bioinformatics, gene disruption and chemical analysis processes. Hence, this work reveals the basis for the synthesis of an understudied class of fungal secondary metabolites and provides a new model species for understanding the synthesis of biaryl compounds with a chiral axis.


mSystems ◽  
2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Jens Christian Nielsen ◽  
Sylvain Prigent ◽  
Sietske Grijseels ◽  
Mhairi Workman ◽  
Boyang Ji ◽  
...  

ABSTRACTFilamentous fungi possess great potential as sources of medicinal bioactive compounds, such as antibiotics, but efficient production is hampered by a limited understanding of how their metabolism is regulated. We investigated the metabolism of six secondary metabolite-producing fungi of thePenicilliumgenus during nutrient depletion in the stationary phase of batch fermentations and assessed conserved metabolic responses across species using genome-wide transcriptional profiling. A coexpression analysis revealed that expression of biosynthetic genes correlates with expression of genes associated with pathways responsible for the generation of precursor metabolites for secondary metabolism. Our results highlight the main metabolic routes for the supply of precursors for secondary metabolism and suggest that the regulation of fungal metabolism is tailored to meet the demands for secondary metabolite production. These findings can aid in identifying fungal species that are optimized for the production of specific secondary metabolites and in designing metabolic engineering strategies to develop high-yielding fungal cell factories for production of secondary metabolites.IMPORTANCESecondary metabolites are a major source of pharmaceuticals, especially antibiotics. However, the development of efficient processes of production of secondary metabolites has proved troublesome due to a limited understanding of the metabolic regulations governing secondary metabolism. By analyzing the conservation in gene expression across secondary metabolite-producing fungal species, we identified a metabolic signature that links primary and secondary metabolism and that demonstrates that fungal metabolism is tailored for the efficient production of secondary metabolites. The insight that we provide can be used to develop high-yielding fungal cell factories that are optimized for the production of specific secondary metabolites of pharmaceutical interest.


2009 ◽  
Vol 4 (9) ◽  
pp. 1934578X0900400 ◽  
Author(s):  
M. Soledade C. Pedras ◽  
Yang Yu

The metabolites produced by the fungal species Leptosphaeria maculans and L. biglobosa under different culture conditions, together with their phytotoxic activities are reviewed. In addition, the biosynthetic studies of blackleg metabolites carried out to date are described and suggestions for species reclassification are provided.


1996 ◽  
Vol 41 (6) ◽  
pp. 494-498 ◽  
Author(s):  
S. Cehulová ◽  
S. Kryštofová ◽  
V. Betina ◽  
L'. Varečka

2021 ◽  
Vol 9 ◽  
Author(s):  
Ronglu Yu ◽  
Jia Liu ◽  
Yi Wang ◽  
Hong Wang ◽  
Huawei Zhang

Aspergillus niger, one of the most common and important fungal species, is ubiquitous in various environments. A. niger isolates possess a large number of cryptic biosynthetic gene clusters (BGCs) and produce various biomolecules as secondary metabolites with a broad spectrum of application fields covering agriculture, food, and pharmaceutical industry. By extensive literature search, this review with a comprehensive summary on biological and chemical aspects of A. niger strains including their sources, BGCs, and secondary metabolites as well as biological properties and biosynthetic pathways is presented. Future perspectives on the discovery of more A. niger-derived functional biomolecules are also provided in this review.


2021 ◽  
Vol 11 (SPL4) ◽  
pp. 900-905
Author(s):  
Satish Kumar Sharma ◽  
Omprakash Goshain

Covid-19, a disease caused by severe acute respiratory syndrome corona virus (SARS-CoV) has challenged pharmaceutical science against viruses, globally. The disease has become a global pandemic beginning the race of new therapeutic strategies against novel corona virus (nCoV). Therefore, management of such pandemic issue is a need of the hour. Drug delivery refers to an approach adopted to transfer drug particles within the body to obtain a potent therapeutic effect. In the present study, an attempt has been taken to discuss about plant secondary metabolites (PSMs) and fungal bioactive compounds which are potent antiviral pharmaceutical agents. Also, a discussion about allopathic ingredient of plant secondary metabolites have also been done. The unique repository of Indian plants and versatility of fungal species provide broad spectrum to screen for pharmaceutical ingredients against novel corona virus. Further, screening of plant secondary metabolites by molecular docking can be a cost effective way to combat from novel corona virus. Thus, it can be said that, Multidimensional approach discussed herein may provide insights to combat antimicrobial resistance in the future. The present review will promote further research horizons in plants and fungal based therapeutics and a novel approach towards drug discovery thereby preventing the humans from suffering through severe adversities.


2022 ◽  
Vol 8 (1) ◽  
pp. 55
Author(s):  
Pierluigi Reveglia ◽  
Maria Luisa Raimondo ◽  
Marco Masi ◽  
Alessio Cimmino ◽  
Genoveffa Nuzzo ◽  
...  

Grapevine (Vitis vinifera L.) can be affected by many different biotic agents, including tracheomycotic fungi such as Phaeomoniella chlamydospora and Phaeoacremonium minimum, which are the main causal agent of Esca and Petri diseases. Both fungi produce phytotoxic naphthalenone polyketides, namely scytalone and isosclerone, that are related to symptom development. The main objective of this study was to investigate the secondary metabolites produced by three Phaeoacremonium species and to assess their phytotoxicity by in vitro bioassay. To this aim, untargeted and targeted LC-MS/MS-based metabolomics were performed. High resolution mass spectrometer UHPLC-Orbitrap was used for the untargeted profiling and dereplication of secondary metabolites. A sensitive multi reaction monitoring (MRM) method for the absolute quantification of scytalone and isosclerone was developed on a UPLC-QTrap. Different isolates of P. italicum, P. alvesii and P. rubrigenum were grown in vitro and the culture filtrates and organic extracts were assayed for phytotoxicity. The toxic effects varied within and among fungal isolates. Isosclerone and scytalone were dereplicated by matching retention times and HRMS and MS/MS data with pure standards. The amount of scytalone and isosclerone differed within and among fungal species. To our best knowledge, this is the first study that applies an approach of LC-MS/MS-based metabolomics to investigate differences in the metabolic composition of organic extracts of Phaeoacremonium species culture filtrates.


Author(s):  
Sara M Stricker ◽  
Bruce D. Gossen ◽  
Mary Ruth McDonald

The fungal genus <i>Stemphylium</i> (phylum Ascomycota, teleomorph <i>Pleospora</i>) includes plant pathogenic, endophytic, and saprophytic species with worldwide distributions. <i>Stemphylium<i></i> spp. produce prodigious numbers of air-borne spores, so are a human health concern as allergens. Some species also produce secondary metabolites such as glucosides, ferric chelates, aromatic polyketides, and others that function as toxins that damage plants and other fungal species. Some of these compounds also exhibit a low level of mammalian toxicity. The high production of air-borne spores by this genus can result in a high incidence of human exposure. Concern about toxin production appears to be the reason that <i></i>S. vesicarium<i></i>, which is a pathogen of several vegetable crops, was classified in Canada as a potential risk of harm to humans for many years. A detailed assessment of the risk of exposure was provided to the relevant regulatory body, Public Health Agency of Canada. They determined that <i></i>Stemphylium<i></i> spp., in nature or under laboratory conditions, posed little to no risk to humans or animals, and the species was re-assigned as a basic (level 1) risk agent.


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