ORCID Profile
0000-0001-7719-7524
Current Organisation
University of Western Australia
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Synthetic Biology | Biochemistry and Cell Biology | Biologically Active Molecules | Biochemistry and cell biology | Natural Products Chemistry | Synthetic biology | Plant Pathology | Natural products and bioactive compounds | Organic Chemistry | Structural biology (incl. macromolecular modelling) | Electrochemistry | Organic Chemical Synthesis | Environmental biotechnology not elsewhere classified | Agricultural Biotechnology | Organometallic Chemistry | Crop and Pasture Improvement (Selection and Breeding) | Animal Nutrition | Industrial microbiology (incl. biofeedstocks) | Agricultural Molecular Engineering of Nucleic Acids and Proteins | Industrial Microbiology (incl. Biofeedstocks)
ANZSRC Socio-Economic Objective (SEO)
Expanding Knowledge in the Biological Sciences | Crop Protection Chemicals | Wheat | Expanding Knowledge in the Chemical Sciences | Human Pharmaceutical Treatments (e.g. Antibiotics) | Sown Pastures (excl. Lucerne) | Dairy Cattle | Veterinary Pharmaceutical Treatments (e.g. Antibiotics) | Sheep - Meat | Expanding Knowledge in the Environmental Sciences |
Related Links
Publications
Acceptance and commitment therapy for late-life treatment-resistant generalised anxiety disorder: a feasibility study
Publisher: Oxford University Press (OUP)
Date: 13-04-2021
Abstract: Generalised anxiety disorder (GAD) is the most common anxiety disorder in older people. First-line management includes pharmacological and psychological therapies, but many do not find these effective or acceptable. Little is known about how to manage treatment-resistant generalised anxiety disorder (TR-GAD) in older people. To examine the acceptability, feasibility and preliminary estimates of the effectiveness of acceptance and commitment therapy (ACT) for older people with TR-GAD. People aged ≥65 years with TR-GAD (defined as not responding to GAD treatment, tolerate it or refused treatment) recruited from primary and secondary care services and the community. Participants received up to 16 one-to-one sessions of ACT, developed specifically for older people with TR-GAD, in addition to usual care. Co-primary outcomes were feasibility (defined as recruitment of ≥32 participants and retention of ≥60% at follow-up) and acceptability (defined as participants attending ≥10 sessions and scoring ≥21/30 on the satisfaction with therapy subscale). Secondary outcomes included measures of anxiety, worry, depression and psychological flexibility (assessed at 0 and 20 weeks). Thirty-seven participants were recruited, 30 (81%) were retained and 26 (70%) attended ≥10 sessions. A total of 18/30 (60%) participants scored ≥21/30 on the satisfaction with therapy subscale. There was preliminary evidence suggesting that ACT may improve anxiety, depression and psychological flexibility. There was evidence of good feasibility and acceptability, although satisfaction with therapy scores suggested that further refinement of the intervention may be necessary. Results indicate that a larger-scale randomised controlled trial of ACT for TR-GAD is feasible and warranted.
A genome-wide survey of the secondary metabolite biosynthesis genes in the wheat pathogen Parastagonospora nodorum.
Publisher: Informa UK Limited
Date: 24-06-2014
Heterologous Expression of Fungal Biosynthetic Pathways in Aspergillus nidulans Using Episomal Vectors
Publisher: Springer US
Date: 2022
DOI: 10.1007/978-1-0716-2273-5_5
Abstract: Filamentous fungi produce a wide ersity of secondary metabolites, whose biosynthesis is encoded in biosynthetic gene clusters (BGCs). As novel BGCs are often found in fungal species that are genetically intractable or difficult to cultivate, heterologous expression is increasingly being used for compound discovery. In addition, heterologous expression is a useful strategy to elucidate the function of the genes within a BGC and shed light on their enzymatic mechanisms. Here, we describe a method for BGC elucidation using multi-marker AMA1-based pYFAC vectors for episomal expression in the fungal host Aspergillus nidulans. The pYFAC vectors have the advantage of high transformation efficiency and support high compound production. In addition, different pathway intermediates can be easily evaluated by testing different vector combinations. This protocol encompasses different AMA1-based strategies for BGC expression such as cloning of a BGC native sequence, promoter exchange or transcription factor overexpression. We also describe procedures for A. nidulans protoplasting, transformation, and small-scale culture analysis of strains containing AMA1 vectors.
Biosynthesis of the pyrrolidine protein synthesis inhibitor anisomycin involves novel gene ensemble and cryptic biosynthetic steps
Publisher: Proceedings of the National Academy of Sciences
Date: 03-04-2017
Abstract: Despite significant advances in the prediction of natural product biosynthetic gene clusters (BGCs) from microbial genomes, challenges remain for those belong to the lesser-known classes. Using a bioactivity-guided library screening approach, we have identified a BGC encoding the biosynthesis of anisomycin, an important pyrrolidine-containing protein synthesis inhibitor. The biosynthetic pathway is distinct from known bacterial alkaloid pathways and involves a class of natural product backbone biosynthesis genes encoding an α-keto acid-incorporating transketolase. A cryptic but crucial glycosylation, unexpected transaminations, and a multistep pyrrolidine-forming reaction catalyzed by a single enzyme are also required to complete the assembly of the core benzylpyrrolidine scaffold. These findings open up new avenues for genomics-guided natural product discovery and engineering of pyrrolidine antibiotics.
Characterization of a Silent Azaphilone Gene Cluster from Aspergillus niger ATCC 1015 Reveals a Hydroxylation-Mediated Pyran-Ring Formation
Publisher: Elsevier BV
Date: 08-2012
The identification and deletion of the polyketide synthase‐nonribosomal peptide synthase gene responsible for the production of the phytotoxic triticone A/B in the wheat fungal pathogen
Publisher:
Wiley
Date:
21-11-2019
Publisher: Wiley
Date: 21-11-2019
Conglobatins B–E: cytotoxic analogues of the C2-symmetric macrodiolide conglobatin
Publisher: Springer Science and Business Media LLC
Date: 17-06-2020
The substrate-dependent stereoselectivity of the multicopper oxidase (MCO)-catalyzed oxidative coupling in the biosynthesis of the bisnaphthopyrone viriditoxin
Publisher: Cold Spring Harbor Laboratory
Date: 18-11-2019
DOI: 10.1101/846196
Abstract: VdtB, the multiple-copper oxidase (MCO) from the bisnaphthopyrone ( M )-viriditoxin biosynthetic pathway in Paecilomyces variotii , was shown to catalyze regioselective 6,6′-coupling of semi-viriditoxin ( 1 ). The stereoselectivity of the oxidative coupling reaction for the production of the atropisomer ( M )-viriditoxin, however, was controlled by VdtD, a non-catalytic dirigent protein from the pathway. In this work, VdtB either alone or together with VdtD were investigated for its stereoselective control upon coupling of other monomeric naphthopyrone derivatives from the pathway with different minor structural variations in terms of presence/absence of O -methylation at C7-position and C3-C4 Δ 2 double bond on the pyrone ring, and the different side-chain modifications. We showed that VdtB could favour either M - or P -form coupling in a substrate-dependent manner. For some substrates, VdtB could catalyze oxidative coupling in an enantiomerically selective manner. The efficiency of the VdtD in exerting stereoselective control of the oxidative coupling reaction also varies between substrates. The results point to a model whereby VdtB and VdtD form a VdtB-ligand-VdtD complex in which the stereochemical outcome of the coupling reaction depends on how the substrate interacts with both proteins, based on the substrate structure. Our findings contributed to a more comprehensive understanding of dirigent protein-mediated MCO-catalyzed stereoselective oxidative coupling reactions in fungi.
cblaster: a remote search tool for rapid identification and visualisation of homologous gene clusters
Publisher: Cold Spring Harbor Laboratory
Date: 09-11-2020
DOI: 10.1101/2020.11.08.370601
Abstract: Genes involved in coordinated biological pathways, including metabolism, drug resistance and virulence, are often collocalised as gene clusters. Identifying homologous gene clusters aids in the study of their function and evolution, however existing tools are limited to searching local sequence databases. Tools for remotely searching public databases are necessary to keep pace with the rapid growth of online genomic data. Here, we present cblaster , a Python based tool to rapidly detect collocated genes in local and remote databases. cblaster is easy to use, offering both a command line and a user-friendly graphical user interface (GUI). It generates outputs that enable intuitive visualisations of large datasets, and can be readily incorporated into larger bioinformatic pipelines. cblaster is a significant update to the comparative genomics toolbox. cblaster source code and documentation is freely available from GitHub under the MIT license (amcil/cblaster).
Navigating the Fungal Polyketide Chemical Space: From Genes to Molecules
Publisher: American Chemical Society (ACS)
Date: 13-09-2012
DOI: 10.1021/JO301592K
Genome Mining of a Prenylated and Immunosuppressive Polyketide from Pathogenic Fungi
Publisher: American Chemical Society (ACS)
Date: 31-01-2013
DOI: 10.1021/OL303435Y
Biosynthesis of bioactive natural products from Basidiomycota
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C8OB02774A
Abstract: The club fungi, Basidioycota, produce a wide range of bioactive compounds. Here, we describe recent studies on the biosynthetic pathways and enzymes of bioactive natural products from these fungi.
Identification and Heterologous Production of a Benzoyl-Primed Tricarboxylic Acid Polyketide Intermediate from the Zaragozic Acid A Biosynthetic Pathway
Publisher: American Chemical Society (ACS)
Date: 13-06-2017
Changing patterns of neuropsychological functioning in children living at high altitude above and below 4000 m: a report from the Bolivian Children Living at Altitude (BoCLA) study.
Publisher: Wiley
Date: 21-07-2011
Genome Mining of Aspergillus hancockii Unearths Cryptic Polyketide Hancockinone A Featuring a Prenylated 6/6/6/5 Carbocyclic Skeleton
Publisher: American Chemical Society (ACS)
Date: 08-11-2021
DOI: 10.1021/ACS.ORGLETT.1C03283
Abstract: Activation of a cryptic polyketide synthase gene cluster
An In Planta -Expressed Polyketide Synthase Produces ( R )-Mellein in the Wheat Pathogen Parastagonospora nodorum
Publisher: American Society for Microbiology
Date: 2015
DOI: 10.1128/AEM.02745-14
Abstract: Parastagonospora nodorum is a pathogen of wheat that affects yields globally. Previous transcriptional analysis identified a partially reducing polyketide synthase (PR-PKS) gene, SNOG_00477 ( SN477 ), in P. nodorum that is highly upregulated during infection of wheat leaves. Disruption of the corresponding SN477 gene resulted in the loss of production of two compounds, which we identified as ( R )-mellein and ( R )- O -methylmellein. Using a Saccharomyces cerevisiae yeast heterologous expression system, we successfully demonstrated that SN477 is the only enzyme required for the production of ( R )-mellein. This is the first identification of a fungal PKS that is responsible for the synthesis of ( R )-mellein. The P. nodorum Δ SN477 mutant did not show any significant difference from the wild-type strain in its virulence against wheat. However, ( R )-mellein at 200 μg/ml inhibited the germination of wheat ( Triticum aestivum ) and barrel medic ( Medicago truncatula ) seeds. Comparative sequence analysis identified the presence of mellein synthase (MLNS) homologues in several Dothideomycetes and two sodariomycete genera. Phylogenetic analysis suggests that the MLNSs in fungi and bacteria evolved convergently from fungal and bacterial 6-methylsalicylic acid synthases.
The global regulator of pathogenesis PnCon7 positively regulates Tox3 effector gene expression through direct interaction in the wheat pathogen Parastagonospora nodorum
Publisher: Wiley
Date: 21-05-2018
DOI: 10.1111/MMI.13968
Abstract: To investigate effector gene regulation in the wheat pathogenic fungus Parastagonospora nodorum, the promoter and expression of Tox3 was characterised through a series of complementary approaches. Promoter deletion and DNase I footprinting experiments identified a 25 bp region in the Tox3 promoter as being required for transcription. Subsequent yeast one-hybrid analysis using the DNA sequence as bait identified that interacting partner as the C2H2 zinc finger transcription factor PnCon7, a putative master regulator of pathogenesis. Silencing of PnCon7 resulted in the down-regulation of Tox3 demonstrating that the transcription factor has a positive regulatory role on gene expression. Analysis of Tox3 expression in the PnCon7 silenced strains revealed a strong correlation with PnCon7 transcript levels, supportive of a direct regulatory role. Subsequent pathogenicity assays using PnCon7-silenced isolates revealed that the transcription factor was required for Tox3-mediated disease. The expression of two other necrotrophic effectors (ToxA and Tox1) was also affected but in a non-dose dependent manner suggesting that the regulatory role of PnCon7 on these genes was indirect. Collectively, these data have advanced our fundamental understanding of the Con7 master regulator of pathogenesis by demonstrating its positive regulatory role on the Tox3 effector in P. nodorum through direct interaction.
CAGECAT: The CompArative GEne Cluster Analysis Toolbox for rapid search and visualisation of homologous gene clusters
Publisher: Springer Science and Business Media LLC
Date: 03-05-2023
DOI: 10.1186/S12859-023-05311-2
Abstract: Co-localized sets of genes that encode specialized functions are common across microbial genomes and occur in genomes of larger eukaryotes as well. Important ex les include Biosynthetic Gene Clusters (BGCs) that produce specialized metabolites with medicinal, agricultural, and industrial value (e.g. antimicrobials). Comparative analysis of BGCs can aid in the discovery of novel metabolites by highlighting distribution and identifying variants in public genomes. Unfortunately, gene-cluster-level homology detection remains inaccessible, time-consuming and difficult to interpret. The comparative gene cluster analysis toolbox (CAGECAT) is a rapid and user-friendly platform to mitigate difficulties in comparative analysis of whole gene clusters. The software provides homology searches and downstream analyses without the need for command-line or programming expertise. By leveraging remote BLAST databases, which always provide up-to-date results, CAGECAT can yield relevant matches that aid in the comparison, taxonomic distribution, or evolution of an unknown query. The service is extensible and interoperable and implements the cblaster and clinker pipelines to perform homology search, filtering, gene neighbourhood estimation, and dynamic visualisation of resulting variant BGCs. With the visualisation module, publication-quality figures can be customized directly from a web-browser, which greatly accelerates their interpretation via informative overlays to identify conserved genes in a BGC query. Overall, CAGECAT is an extensible software that can be interfaced via a standard web-browser for whole region homology searches and comparison on continually updated genomes from NCBI. The public web server and installable docker image are open source and freely available without registration at: cagecat.bioinformatics.nl .
Fungal Dirigent Protein Controls the Stereoselectivity of Multicopper Oxidase-Catalyzed Phenol Coupling in Viriditoxin Biosynthesis
Publisher: American Chemical Society (ACS)
Date: 02-05-2019
DOI: 10.1021/JACS.9B03354
Abstract: Paecilomyces variotii produces the antibacterial and cytotoxic ( M)-viriditoxin (1) together with a trace amount of its atropisomer ( P)-viriditoxin 1'. Elucidation of the biosynthesis by heterologous pathway reconstruction in Aspergillus nidulans identified the multicopper oxidase (MCO) VdtB responsible for the regioselective 6,6'-coupling of semiviriditoxin (10), which yielded 1 and 1' at a ratio of 1:2. We further uncovered that VdtD, an α/β hydrolase-like protein lacking the catalytic serine, directs the axial chirality of the products. Using recombinant VdtB and VdtD as cell-free extracts from A. nidulans, we demonstrated that VdtD acts like a dirigent protein to control the stereoselectivity of the coupling catalyzed by VdtB to yield 1 and 1' at a ratio of 20:1. Furthermore, we uncovered a unique Baeyer-Villiger monooxygenase (BVMO) VdtE that could transform the alkyl methylketone side chain to methyl ester against the migratory aptitude.
CRISPR-Mediated Activation of Biosynthetic Gene Clusters for Bioactive Molecule Discovery in Filamentous Fungi
Publisher: American Chemical Society (ACS)
Date: 11-06-2020
Functional redundancy of necrotrophic effectors – consequences for exploitation for breeding
Publisher: Frontiers Media SA
Date: 08-07-2015
The past, present and future of secondary metabolite research in the Dothideomycetes
Publisher: Wiley
Date: 07-07-2014
DOI: 10.1111/MPP.12162
Acquisition and Loss of Secondary Metabolites Shaped the Evolutionary Path of Three Emerging Phytopathogens of Wheat
Publisher: Oxford University Press (OUP)
Date: 21-02-2019
DOI: 10.1093/GBE/EVZ037
Elucidation of the Concise Biosynthetic Pathway of the Communesin Indole Alkaloids
Publisher: Wiley
Date: 08-01-2015
Panning for gold in mould: can we increase the odds for fungal genome mining?
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C7OB03127K
Abstract: A perspective on existing and emerging strategies for the prioritisation of secondary metabolite biosynthetic gene clusters (BGCs) to increase the odds of fruitful mining of fungal genomes.
Neurophysiological evidence for cognitive and brain functional adaptation in adolescents living at high altitude
Publisher: Elsevier BV
Date: 09-2011
Complexity Generation in Fungal Polyketide Biosynthesis: A Spirocycle-Forming P450 in the Concise Pathway to the Antifungal Drug Griseofulvin
Publisher: American Chemical Society (ACS)
Date: 09-09-2013
DOI: 10.1021/CB400541Z
Cre/lox-Mediated Chromosomal Integration of Biosynthetic Gene Clusters for Heterologous Expression in Aspergillus nidulans
Publisher: American Chemical Society (ACS)
Date: 16-02-2022
DOI: 10.1021/ACSSYNBIO.1C00458
Abstract: Building strains of filamentous fungi for stable long-term heterologous expression of large biosynthetic pathways is limited by the low transformation efficiency or genetic stability of current methods. Here, we developed a system for targeted chromosomal integration of large biosynthetic gene clusters in
Fungal Planet description sheets: 1042–1111
Publisher: Naturalis Biodiversity Center
Date: 29-06-2020
DOI: 10.3767/PERSOONIA.2020.44.11
Abstract: Novel species of fungi described in this study include those from various countries as follows: Antarctica , Cladosporium arenosum from marine sediment sand. Argentina , Kosmimatamyces alatophylus (incl. Kosmimatamyces gen. nov.) from soil. Australia , Aspergillus banksianus , Aspergillus kumbius , Aspergillus luteorubrus , Aspergillus malvicolor and Aspergillus nanangensis from soil, Erysiphe medicaginis from leaves of Medicago polymorpha , Hymenotorrendiella communis on leaf litter of Eucalyptus bicostata , Lactifluus albopicri and Lactifluus austropiperatus on soil, Macalpinomyces collinsiae on Eriachne benthamii , Marasmius vagus on soil, Microdochium dawsoniorum from leaves of Sporobolus natalensis , Neopestalotiopsis nebuloides from leaves of Sporobolus elongatus , Pestalotiopsis etonensis from leaves of Sporobolus jacquemontii , Phytophthora personensis from soil associated with dying Grevillea mccutcheonii. Brazil , Aspergillus oxumiae from soil, Calvatia baixaverdensis on soil, Geastrum calycicoriaceum on leaf litter, Greeneria kielmeyerae on leaf spots of Kielmeyera coriacea . Chile , Phytophthora aysenensis on collar rot and stem of Aristotelia chilensis . Croatia , Mollisia gibbospora on fallen branch of Fagus sylvatica . Czech Republic , Neosetophoma hnaniceana from Buxus sempervirens . Ecuador , Exophiala frigidotolerans from soil. Estonia , Elaphomyces bucholtzii in soil. France , Venturia paralias from leaves of Euphorbia paralias . India , Cortinarius balteatoindicus and Cortinarius ulkhagarhiensis on leaf litter. Indonesia , Hymenotorrendiella indonesiana on Eucalyptus urophylla leaf litter. Italy , Penicillium taurinense from indoor chestnut mill. Malaysia , Hemileucoglossum kelabitense on soil, Satchmopsis pini on dead needles of Pinus tecunumanii . Poland , Lecanicillium praecognitum on insects' frass. Portugal , Neodevriesia aestuarina from saline water. Republic of Korea , Gongronella namwonensis from freshwater. Russia , Candida pellucida from Exomias pellucidus , Heterocephalacria septentrionalis as endophyte from Cladonia rangiferina , Vishniacozyma phoenicis from dates fruit, Volvariella paludosa from sw . Slovenia , Mallocybe crassivelata on soil. South Africa , Beltraniella podocarpi , Hamatocanthoscypha podocarpi , Coleophoma podocarpi and Nothoseiridium podocarpi (incl. Nothoseiridium gen. nov.)from leaves of Podocarpus latifolius , Gyrothrix encephalarti from leaves of Encephalartos sp., Paraphyton cutaneum from skin of human patient, Phacidiella alsophilae from leaves of Alsophila capensis , and Satchmopsis metrosideri on leaf litter of Metrosideros excelsa. Spain , Cladophialophora cabanerensis from soil, Cortinarius paezii on soil, Cylindrium magnoliae from leaves of Magnolia grandiflora , Trichophoma cylindrospora (incl. Trichophoma gen. nov.) from plant debris, Tuber alcaracense in calcareus soil, Tuber buendiae in calcareus soil. Thailand , Annulohypoxylon spougei on corticated wood, Poaceascoma filiforme from leaves of unknown Poaceae. UK , Dendrostoma luteum on branch lesions of Castanea sativa , Ypsilina buttingtonensis from heartwood of Quercus sp. Ukraine , Myrmecridium phragmiticola from leaves of Phragmites australis. USA , Absidia pararepens from air, Juncomyces californiensis (incl. Juncomyces gen. nov.) from leaves of Juncus effusus , Montagnula cylindrospora from a human skin s le, Muriphila oklahomaensis (incl. Muriphila gen. nov.)on outside wall of alcohol distillery, Neofabraea eucalyptorum from leaves of Eucalyptus macrandra , Diabolocovidia claustri (incl. Diabolocovidia gen. nov.)from leaves of Serenoa repens , Paecilomyces penicilliformis from air, Pseudopezicula betulae from leaves of leaf spots of Populus tremuloides . Vietnam , Diaporthe durionigena on branches of Durio zibethinus and Roridomyces pseudoirritans on rotten wood. Morphological and culture characteristics are supported by DNA barcodes.
CAGECAT: The CompArative GEne Cluster Analysis Toolbox for rapid search and visualisation of homologous gene clusters
Publisher: Cold Spring Harbor Laboratory
Date: 10-02-2023
DOI: 10.1101/2023.02.08.527634
Abstract: Co-localized sets of genes that encode specialized functions are common across microbial genomes and occur in genomes of larger eukaryotes as well. Important ex les include Biosynthetic Gene Clusters (BGCs) that produce specialized metabolites with medicinal, agricultural, and industrial value (e.g. antimicrobials). Comparative analysis of BGCs can aid in the discovery of novel metabolites by highlighting distribution and identifying variants in public genomes. Unfortunately, gene-cluster-level homology detection remains inaccessible, time-consuming and difficult to interpret. The comparative gene cluster analysis toolbox (CAGECAT) is a rapid and user-friendly platform to mitigate difficulties in comparative analysis of whole gene clusters. The software provides homology searches and downstream analyses without the need for command-line or programming expertise. By leveraging remote BLAST databases, which always provide up-to-date results, CAGECAT can yield relevant matches that aid in the comparison, taxonomic distribution, or evolution of an unknown query. The service is extensible and interoperable and implements the cblaster and clinker pipelines to perform homology search, filtering, gene neighbourhood estimation, and dynamic visualisation of resulting variant BGCs. With the visualisation module, publication-quality figures can be customized directly from a web-browser, which greatly accelerates their interpretation via informative overlays to identify conserved genes in a BGC query. Overall, CAGECAT is an extensible software that can be interfaced via a standard web-browser for whole region homology searches and comparison on continually updated genomes from NCBI. The public web server and installable docker image are open source and freely available without registration at: cagecat.bioinformatics.nl
Bipolenins K-N
Publisher: Beilstein Institut
Date: 26-08-2019
DOI: 10.3762/BJOC.15.198
Abstract: Chemical investigation of the barley and wheat fungal pathogen Bipolaris sorokiniana BRIP10943 yielded four new sativene-type sesquiterpenoid natural products, bipolenins K–N ( 1 – 4 ), together with seven related known analogues ( 5 – 11 ), and a sesterterpenoid ( 12 ). Their structures were determined by detailed analysis of spectroscopic data, supported by TDDFT calculations and comparison with previously reported analogues. These compounds were evaluated for their phytotoxic activity against wheat seedlings and wheat seed germination. The putative biosynthetic relationships between the isolated sesquiterpenoids were also explored.
Co-creating value in online innovation communities
Publisher: Emerald
Date: 10-06-2019
Abstract: Online innovation communities are central for many organizations seeking to advance their innovation portfolio. While these communities rely on consumers to collaborate in the innovation process, it remains unclear what drives these consumers to perform value co-creation activities and what value dimensions they derive as a result. This paper aims to advance the understanding of value co-creation in the online collaborative innovation context. Specifically, it aims to examine social and in idual factors driving such activities, and the value derived from the perspective of the member. A self-administered online questionnaire was used to collect data from collaborative innovation community members yielding 309 complete responses. Structural equation modelling was used to analyse the data, using variance-based structural equation modelling with partial least squares path modelling in SmartPLS. Results confirm that distinct social and in idual factors facilitate in idual value co-creation activities, including the provision of feedback, helping, rapport building and information sharing. Furthermore, the research confirms the mediating role of learning on these relationships. This study contributes to the micro-foundation movement in marketing by undertaking an independent examination of value co-creation activities and their nomological network. A shift in the mindset of managing for collaborative innovation is required, from a focus on collaborative product development to the management of an online community where members derive value from their co-creation activities. This research is the first to offer insight into important in idual and social pre-conditions and subsequent value outcomes of four common value co-creation activities. It informs practice about how to facilitate value co-creation activities and contribute to the co-creation of value for online innovation community members.
Discovery of brevijanazines from Aspergillus brevijanus reveals the molecular basis for p-nitrobenzoic acid in fungi
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2CC01679F
Abstract: The discovery of a novel family of p -nitrobenzoylated piperazines from Aspergillus brevijanus revealed that the biosynthesis of p -nitrobenzoic acid in fungi is catalysed by a PABA synthase, an aminodeoxychorismate synthase and a cytochrome P450.
Biosynthesis of a New Benzazepine Alkaloid Nanangelenin A from Aspergillus nanangensis Involves an Unusual l-Kynurenine-Incorporating NRPS Catalyzing Regioselective Lactamization
Publisher: American Chemical Society (ACS)
Date: 17-03-2020
DOI: 10.1021/JACS.0C01605
Chlorinated metabolites from Streptomyces sp. highlight the role of biosynthetic mosaics and superclusters in the evolution of chemical diversity
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1OB00600B
Abstract: Biosynthetic mosaics and superclusters provide rare insights into the evolution of microbial chemical ersity.
A Cytochrome P450 Serves as an Unexpected Terpene Cyclase during Fungal Meroterpenoid Biosynthesis
Publisher: American Chemical Society (ACS)
Date: 11-2013
DOI: 10.1021/JA408966T
RiPP-ing through the plant kingdom
Publisher: Springer Science and Business Media LLC
Date: 22-11-2021
Polyketides produced by the entomopathogenic fungus Metarhizium anisopliae induce Candida albicans growth
Publisher: Elsevier BV
Date: 07-2021
A Multifunctional Monooxygenase XanO4 Catalyzes Xanthone Formation in Xantholipin Biosynthesis via a Cryptic Demethoxylation
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.CHEMBIOL.2016.03.013
Abstract: Xantholipin and several related polycyclic xanthone antibiotics feature a unique xanthone ring nucleus within a highly oxygenated, angular, fused hexacyclic system. In this study, we demonstrated that a flavin-dependent monooxygenase (FMO) XanO4 catalyzes the oxidative transformation of an anthraquinone to a xanthone system during the biosynthesis of xantholipin. In vitro isotopic labeling experiments showed that the reaction involves sequential insertion of two oxygen atoms, accompanied by an unexpected cryptic demethoxylation reaction. Moreover, characterizations of homologous FMOs of XanO4 suggested the generality of the XanO4-like-mediated reaction for the assembly of a xanthone ring in the biosynthesis of polycyclic xanthone antibiotics. These findings not only expand the repertoire of FMO activities but also reveal a novel mechanism for xanthone ring formation.
Identification and Characterization of the Echinocandin B Biosynthetic Gene Cluster from Emericella rugulosa NRRL 11440
Publisher: American Chemical Society (ACS)
Date: 10-2012
DOI: 10.1021/JA307220Z
Victorin, the host-selective cyclic peptide toxin from the oat pathogen Cochliobolus victoriae , is ribosomally encoded
Publisher: Proceedings of the National Academy of Sciences
Date: 14-09-2020
Abstract: Studies of the 1940s Victoria blight of oats epidemic discovered that some fungal pathogens secrete HSTs responsible for symptom development and specificity of the associated disease. The causal necrotrophic pathogen of Victoria blight, C. victoriae , secretes the peptide HST victorin, which was, subsequently, shown to constitute a novel class of effectors that exploit host immunity pathways aimed at repelling biotrophic pathogens. Although these discoveries have broadened our mechanistic understanding of plant-pathogen interactions, the genetic and biochemical origins of victorin have remained elusive. Here, we solve this decades-old mystery by demonstrating that victorin is produced ribosomally, not, as assumed, by nonribosomal peptide synthetase. Furthermore, we identify a CAO enzyme responsible for converting victorin to its active form.
Identification and engineering of the cytochalasin gene cluster from Aspergillus clavatus NRRL 1
Publisher: Elsevier BV
Date: 11-2011
Effect of a reduced fat and sugar maternal dietary intervention during lactation on the infant gut microbiome
Publisher: Frontiers Media SA
Date: 17-08-2022
DOI: 10.3389/FMICB.2022.900702
Abstract: A growing body of literature has shown that maternal diet during pregnancy is associated with infant gut bacterial composition. However, whether maternal diet during lactation affects the exclusively breastfed infant gut microbiome remains understudied. This study sets out to determine whether a two-week of a reduced fat and sugar maternal dietary intervention during lactation is associated with changes in the infant gut microbiome composition and function. Stool s les were collected from four female and six male ( n = 10) infants immediately before and after the intervention. Maternal baseline diet from healthy mothers aged 22–37 was assessed using 24-h dietary recall. During the 2-week dietary intervention, mothers were provided with meals and their dietary intake was calculated using FoodWorks 10 Software. Shotgun metagenomic sequencing was used to characterize the infant gut microbiome composition and function. In all but one participant, maternal fat and sugar intake during the intervention were significantly lower than at baseline. The functional capacity of the infant gut microbiome was significantly altered by the intervention, with increased levels of genes associated with 28 bacterial metabolic pathways involved in biosynthesis of vitamins ( p = 0.003), amino acids ( p = 0.005), carbohydrates ( p = 0.01), and fatty acids and lipids ( p = 0.01). Although the dietary intervention did not affect the bacterial composition of the infant gut microbiome, relative difference in maternal fiber intake was positively associated with increased abundance of genes involved in biosynthesis of storage compounds ( p = 0.016), such as cyanophycin. Relative difference in maternal protein intake was negatively associated with Veillonella parvula ( p = 0.006), while positively associated with Klebsiella michiganensis ( p = 0.047). Relative difference in maternal sugar intake was positively associated with Lactobacillus paracasei ( p = 0.022). Relative difference in maternal fat intake was positively associated with genes involved in the biosynthesis of storage compounds ( p = 0.015), fatty acid and lipid ( p = 0.039), and metabolic regulator ( p = 0.038) metabolic pathways. This pilot study demonstrates that a short-term maternal dietary intervention during lactation can significantly alter the functional potential, but not bacterial taxonomy, of the breastfed infant gut microbiome. While the overall diet itself was not able to change the composition of the infant gut microbiome, changes in intakes of maternal protein and sugar during lactation were correlated with changes in the relative abundances of certain bacterial species. Clinical trial registration: Australian New Zealand Clinical Trials Registry (ACTRN12619000606189).
Elucidation of Piericidin A1 Biosynthetic Locus Revealed a Thioesterase-Dependent Mechanism of α-Pyridone Ring Formation
Publisher: Elsevier BV
Date: 02-2012
DOI: 10.1016/J.CHEMBIOL.2011.12.018
Abstract: Piericidins are a class of α-pyridone antibiotics that inhibit mitochondrial respiratory chain and exhibit antimicrobial, antifungal, and antitumor activities. Sequential analysis of Streptomyces piomogeues var. Hangzhouwanensis genome revealed six modular polyketide synthases, an amidotransferase, two methyltransferases, and a monooxygenase for piericidin A1 production. Gene functional analysis and deletion results provide overview of the biosynthesis pathway. Furthermore, in vitro characterization of the terminal polyketide synthase module with the thioesterase domain using β-ketoacyl substrates was performed. That revealed a pathway where the α-pyridone ring formation is dependent on hydrolysis of the product β, δ-diketo carboxylic acid by the C-terminal thioesterase followed by amidation and cyclization. These findings set the stage to investigate unusual enzymatic mechanisms in α-pyridone antibiotics biosynthesis, provide a foundation for genome mining of α-pyridone antibiotics, and produce analogs by molecular engineering.
Transcriptome Analysis Revealed Highly Expressed Genes Encoding Secondary Metabolite Pathways and Small Cysteine-Rich Proteins in the Sclerotium of Lignosus rhinocerotis
Publisher: Public Library of Science (PLoS)
Date: 25-11-2015
cblaster: a remote search tool for rapid identification and visualization of homologous gene clusters
Publisher: Oxford University Press (OUP)
Date: 2021
Abstract: Genes involved in coordinated biological pathways, including metabolism, drug resistance and virulence, are often collocalized as gene clusters. Identifying homologous gene clusters aids in the study of their function and evolution, however, existing tools are limited to searching local sequence databases. Tools for remotely searching public databases are necessary to keep pace with the rapid growth of online genomic data. Here, we present cblaster, a Python-based tool to rapidly detect collocated genes in local and remote databases. cblaster is easy to use, offering both a command line and a user-friendly graphical user interface. It generates outputs that enable intuitive visualizations of large datasets and can be readily incorporated into larger bioinformatic pipelines. cblaster is a significant update to the comparative genomics toolbox. cblaster source code and documentation is freely available from GitHub under the MIT license (amcil/cblaster). Supplementary data are available at Bioinformatics Advances online.
clinker & clustermap.js: automatic generation of gene cluster comparison figures
Publisher: Oxford University Press (OUP)
Date: 18-01-2021
DOI: 10.1093/BIOINFORMATICS/BTAB007
Abstract: Genes involved in biological pathways are often collocalised in gene clusters, the comparison of which can give valuable insights into their function and evolutionary history. However, comparison and visualization of gene cluster similarity is a tedious process, particularly when many clusters are being compared. Here, we present clinker, a Python based tool and clustermap.js, a companion JavaScript visualization library, which used together can automatically generate accurate, interactive, publication-quality gene cluster comparison figures directly from sequence files. Source code and documentation for clinker and clustermap.js is available on GitHub (amcil/clinker and amcil/clustermap.js, respectively) under the MIT license. clinker can be installed directly from the Python Package Index via pip. Supplementary data are available at Bioinformatics online.
Adaptation to Life in the High Andes: Nocturnal Oxyhemoglobin Saturation in Early Development
Publisher: Oxford University Press (OUP)
Date: 05-2016
DOI: 10.5665/SLEEP.5740
Characterisation and heterologous biosynthesis of burnettiene A, a new polyene-decalin polyketide from Aspergillus burnettii
Publisher: American Chemical Society (ACS)
Date: 07-09-2021
DOI: 10.26434/CHEMRXIV-2021-P016T
Abstract: Chemical exploration of the recently described Australian fungus, Aspergillus burnettii, uncovered a new metabolite, burnettiene A. Here, we characterise the structure of burnettiene A as a polyene-decalin polyketide. Bioinformatic analysis of the genome of A. burnettii identified a putative biosynthetic gene cluster for burnettiene A (bue), consisting of eight genes and sharing similarity to the fusarielin gene cluster. Introduction of the reassembled bue gene cluster into Aspergillus nidulans for heterologous expression resulted in the production of burnettiene A under native promoters. Omission of bueE encoding a cytochrome P450 led to the production of preburnettiene A, confirming that BueE is responsible for catalysing the regiospecific multi-oxidation of terminal methyl groups to carboxylic acids. Similarly, bueF was shown to encode an ester-forming methyltransferase, with its omission resulting in the production of the tricarboxylic acid, preburnettiene B. Introduction of an additional copy of the transcription factor bueR under the regulation of the gpdA promoter significantly improved the heterologous production of the burnettienes. Burnettiene A displayed strong in vitro cytotoxicity against mouse myeloma NS-1 cells (MIC 0.8 µg/mL).
Comparative Characterization of Fungal Anthracenone and Naphthacenedione Biosynthetic Pathways Reveals an α-Hydroxylation-Dependent Claisen-like Cyclization Catalyzed by a Dimanganese Thioesterase
Publisher: American Chemical Society (ACS)
Date: 14-09-2011
DOI: 10.1021/JA206906D
Fungal Indole Alkaloid Biosynthesis: Genetic and Biochemical Investigation of the Tryptoquialanine Pathway in Penicillium aethiopicum
Publisher: American Chemical Society (ACS)
Date: 07-02-2011
DOI: 10.1021/JA1101085
Characterisation and heterologous biosynthesis of burnettiene A, a new polyene-decalin polyketide from Aspergillus burnettii
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1OB01766G
Abstract: Burnettiene A is a novel cytotoxic tridecaketide decalin polyketide from Aspergillus burnettii . Its biosynthesis was elucidated by heterologous expression in fungi.
Out for a RiPP: challenges and advances in genome mining of ribosomal peptides from fungi
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D1NP00048A
Abstract: This Highlight reviews previous discoveries of ribosomal peptides in fungi, groups these natural products into three distinct families based on their unique properties and outlines how to leverage these properties for genome mining.
Chemical Ecogenomics-Guided Discovery of Phytotoxic α-Pyrones from the Fungal Wheat Pathogen Parastagonospora nodorum
Publisher: American Chemical Society (ACS)
Date: 18-09-2018
DOI: 10.1021/ACS.ORGLETT.8B02617
Abstract: A biosynthetic gene cluster that is significantly upregulated in the fungal wheat pathogen Parastagonospora nodorum during plant infection was reconstructed heterologously in Aspergillus nidulans. This led to the discovery of five new α-pyrone polyketides, alternapyrones B-F (2-6). Compounds 5 and 6, which contain a highly substituted dihydrofuran, exhibited phytotoxicity on wheat seed germination. It is demonstrated that only three enzymes, one highly reducing polyketide synthase and two multifunctional P450 oxygenases, are needed to synthesize the structurally complex products.
Comprehensive chemotaxonomic and genomic profiling of a biosynthetically talented Australian fungus, Aspergillus burnettii sp. nov
Publisher: Elsevier BV
Date: 10-2020
Assistive technology and telecare to maintain independent living at home for people with dementia: the ATTILA RCT
Publisher: National Institute for Health and Care Research
Date: 03-2021
DOI: 10.3310/HTA25190
Abstract: Assistive technology and telecare have been promoted to manage the risks associated with independent living for people with dementia, but there is limited evidence of their effectiveness. This trial aimed to establish whether or not assistive technology and telecare assessments and interventions extend the time that people with dementia can continue to live independently at home and whether or not they are cost-effective. Caregiver burden, the quality of life of caregivers and of people with dementia and whether or not assistive technology and telecare reduce safety risks were also investigated. This was a pragmatic, randomised controlled trial. Blinding was not undertaken as it was not feasible to do so. All consenting participants were included in an intention-to-treat analysis. This trial was set in 12 councils in England with adult social services responsibilities. Participants were people with dementia living in the community who had an identified need that might benefit from assistive technology and telecare. Participants were randomly assigned to receive either assistive technology and telecare recommended by a health or social care professional to meet their assessed needs (a full assistive technology and telecare package) or a pendant alarm, non-monitored smoke and carbon monoxide detectors and a key safe (a basic assistive technology and telecare package). The primary outcomes were time to admission to care and cost-effectiveness. Secondary outcomes assessed caregivers using the 10-item Center for Epidemiological Studies Depression Scale, the State–Trait Anxiety Inventory 6-item scale and the Zarit Burden Interview. Of 495 participants, 248 were randomised to receive full assistive technology and telecare and 247 received the limited control. Comparing the assistive technology and telecare group with the control group, the hazard ratio for institutionalisation was 0.76 (95% confidence interval 0.58 to 1.01 p = 0.054). After adjusting for an imbalance in the baseline activities of daily living score between trial arms, the hazard ratio was 0.84 (95% confidence interval 0.63 to 1.12 p = 0.20). At 104 weeks, there were no significant differences between groups in health and social care resource use costs (intervention group – control group difference: mean –£909, 95% confidence interval –£5336 to £3345) or in societal costs (intervention group – control group difference: mean –£3545 95% confidence interval –£13,914 to £6581). At 104 weeks, based on quality-adjusted life-years derived from the participant-rated EuroQol-5 Dimensions questionnaire, the intervention group had 0.105 (95% confidence interval –0.204 to –0.007) fewer quality-adjusted life-years than the control group. The number of quality-adjusted life-years derived from the proxy-rated EuroQol-5 Dimensions questionnaire did not differ between groups. Caregiver outcomes did not differ between groups over 24 weeks. Compliance with the assigned trial arm was variable, as was the quality of assistive technology and telecare needs assessments. Attrition from assessments led to data loss additional to that attributable to care home admission and censoring events. A full package of assistive technology and telecare did not increase the length of time that participants with dementia remained in the community, and nor did it decrease caregiver burden, depression or anxiety, relative to a basic package of assistive technology and telecare. Use of the full assistive technology and telecare package did not increase participants’ health and social care or societal costs. Quality-adjusted life-years based on participants’ EuroQol-5 Dimensions questionnaire responses were reduced in the intervention group compared with the control group groups did not differ in the number of quality-adjusted life-years based on the proxy-rated EuroQol-5 Dimensions questionnaire. Future work could examine whether or not improved assessment that is more personalised to an in idual is beneficial. Current Controlled Trials ISRCTN86537017. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 25, No. 19. See the NIHR Journals Library website for further project information.
Discovery of Cryptic Polyketide Metabolites from Dermatophytes Using Heterologous Expression in Aspergillus nidulans
Publisher: American Chemical Society (ACS)
Date: 11-06-2013
DOI: 10.1021/SB400048B
The genome of Micrococcus luteus MST-118984C isolated from Australian soil harbours a bacteriocin biosynthetic gene cluster and biocide/multidrug efflux genes
Publisher: Elsevier BV
Date: 09-2021
Adding the Lipo to Lipopeptides: Do More with Less
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1016/J.CHEMBIOL.2010.08.001
Abstract: Surfactin is a member of the lipopeptide family of antibiotics, which includes the clinical drug daptomycin (Cubicin). The potency of these antibiotics is affected by the attached lipid chain, which is incorporated into the nonribosomally assembled peptidyl backbone via a process known as lipoinitiation. Kraas et al. (2010) have provided valuable insights into the lipoinitiation mechanism, which will be useful for future biosynthetic modifications of lipopeptide antibiotics.
Discovery, bioactivity and biosynthesis of fungal piperazines
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D2NP00070A
Abstract: Fungi are prolific producers of piperazine alkaloids, with more than 90 ex les isolated to date. This review summarises the current knowledge of the discovery, classification, bioactivity and biosynthesis of fungal piperazines up to July of 2022.
LovG: The Thioesterase Required for Dihydromonacolin L Release and Lovastatin Nonaketide Synthase Turnover in Lovastatin Biosynthesis
Publisher: Wiley
Date: 07-05-2013
Efficient Biosynthesis of Fungal Polyketides Containing the Dioxabicyclo-octane Ring System
Publisher: American Chemical Society (ACS)
Date: 10-09-2015
DOI: 10.1021/JACS.5B07816
Cloning and sequence characterization of a non-reducing polyketide synthase gene from the lichen Xanthoparmelia semiviridis
Publisher: Elsevier BV
Date: 02-2008
DOI: 10.1016/J.MYCRES.2007.08.022
Abstract: Lichens produce a erse array of secondary metabolites that have shown various biological activities. Of particular interest are the coupled phenolics that originate from polyketide pathways, such as depsides, depsidones and usnic acids, which are produced almost solely by lichens. Based on the presumed catalytic domains required for the synthesis of the key intermediates beta-orsellinic acid and methylphloroacetophenone, two pairs of degenerate primers were designed to target specifically the beta-ketoacylsynthase (KS) and C-methyltransferase (CMeT) domains of fungal non-reducing polyketide synthase (NR-PKS) genes with CMeT domains. These primers were used to explore the genome of the lichen Xanthoparmelia semiviridis, which produces beta-orcinol depsidones and usnic acid. One of the two KS domains lified from genomic DNA of field-collected X. semiviridis was used as a probe to recover the candidate PKS gene. A 13 kb fragment containing an intact putative PKS gene (xsepks1) of 6555 bp was recovered from a partial genomic library. The inferred amino acid sequence indicated that xsepks1 encodes a protein of 2164 amino acids and contains KS, acyltransferase (AT), acyl carrier protein (ACP) and CMeT domains as expected. This demonstrated a successful strategy for targeting non-reducing PKS genes with CMeT domains. Integration of the 5' fragment of xsepks1, including the native promoter, into Aspergillus nidulans by cotransformation resulted in the transcription of the 5'xsepks1 and the splicing of a 63 bp intron, suggesting that A. nidulans could be a suitable heterologous host for xsepks1 expression.
Volatile Molecules Secreted by the Wheat Pathogen Parastagonospora nodorum Are Involved in Development and Phytotoxicity
Publisher: Frontiers Media SA
Date: 25-03-2020
Cognitive and neuropsychiatric effects of noradrenergic treatment in Alzheimer’s disease: systematic review and meta-analysis
Publisher: BMJ
Date: 05-07-2022
Abstract: Dysfunction of the locus coeruleus-noradrenergic system occurs early in Alzheimer’s disease, contributing to cognitive and neuropsychiatric symptoms in some patients. This system offers a potential therapeutic target, although noradrenergic treatments are not currently used in clinical practice. To assess the efficacy of drugs with principally noradrenergic action in improving cognitive and neuropsychiatric symptoms in Alzheimer’s disease. The MEDLINE, Embase and ClinicalTrials.gov databases were searched from 1980 to December 2021. We generated pooled estimates using random effects meta-analyses. We included 19 randomised controlled trials (1811 patients), of which six were judged as ‘good’ quality, seven as ‘fair’ and six ‘poor’. Meta-analysis of 10 of these studies (1300 patients) showed a significant small positive effect of noradrenergic drugs on global cognition, measured using the Mini-Mental State Examination or Alzheimer’s Disease Assessment Scale—Cognitive Subscale (standardised mean difference (SMD): 0.14, 95% CI: 0.03 to 0.25, p=0.01 I 2 =0%). No significant effect was seen on measures of attention (SMD: 0.01, 95% CI: −0.17 to 0.19, p=0.91 I 2 =0). The apathy meta-analysis included eight trials (425 patients) and detected a large positive effect of noradrenergic drugs (SMD: 0.45, 95% CI: 0.16 to 0.73, p=0.002 I 2 =58%). This positive effect was still present following removal of outliers to account for heterogeneity across studies. Repurposing of established noradrenergic drugs is most likely to offer effective treatment in Alzheimer’s disease for general cognition and apathy. However, several factors should be considered before designing future clinical trials. These include targeting of appropriate patient subgroups and understanding the dose effects of in idual drugs and their interactions with other treatments to minimise risks and maximise therapeutic effects. CRD42021277500.
Fungal Polyketide Synthase Product Chain-Length Control by Partnering Thiohydrolase
Publisher: American Chemical Society (ACS)
Date: 29-05-2014
DOI: 10.1021/CB500284T
Fungal Polyketide-Nonribosomal Peptide Synthetases and Their Associated Natural Products
Publisher: Elsevier
Date: 2020
Acquisition and loss of secondary metabolite clusters shaped the evolutionary path of three recently emerged phytopathogens of wheat
Publisher: Cold Spring Harbor Laboratory
Date: 18-03-2018
DOI: 10.1101/283416
Abstract: White grain disorder is a recently emerged wheat disease in Australia, caused by three Botryosphaeriaceae spp. Eutiarosporella darliae, E. pseudodarliae , and E. tritici-australis . The disease cycle of these pathogens and the molecular basis of their interaction with wheat are poorly understood. To address this, we undertook a comparative genomics approach to identify potential pathogenicity factors. Subsequent genome analysis revealed that each of the white grain disorder species harbour modular polyketide synthase genes. To our knowledge, this is the first report of fungi harbouring such genes. Further comparative analysis using the modular polyketide synthase genes discovered their presence in the closely related Macrophomina phaseolina . Phylogenetic analysis implicates horizontal acquisition of these genes from a bacterial or a protist species. Both E. darliae and E. pseudodarliae possess a secondary metabolite cluster with multiple polyketide/non-ribosomal peptide synthase genes ( Hybrid-1, -2, and -3 ). In contrast, only remnant and partial genes homologous to this cluster were identified at a syntenic locus in E. tritici-australis suggesting loss of this cluster. Homologues of Hybrid-2 in other fungi have been proposed to facilitate disease induction in woody plants. Subsequent assays confirmed that E. darliae and E. pseudodarliae were both pathogenic on woody plant hosts, but E. tritici-australis was not, implicating woody plants as potential host reservoirs for the fungi. We hypothesise that loss of the cluster in E. tritici-australis represents a committed lifestyle jump to grasses. Combined, our observations relating to the secondary metabolite potential of the WGD Eutiarosporella spp. have contributed novel data to the field by expanding the range of known fungal secondary metabolite genes, and helped develop our understanding of the lifestyle and potential host-range of a recently emerged pathogen of wheat.
Generation of Complexity in Fungal Terpene Biosynthesis: Discovery of a Multifunctional Cytochrome P450 in the Fumagillin Pathway
Publisher: American Chemical Society (ACS)
Date: 11-03-2014
DOI: 10.1021/JA500881E
Biosynthesis of a Tricyclo[6.2.2.02,7]dodecane System by a Berberine Bridge Enzyme-Like Aldolase
Publisher: Wiley
Date: 28-10-2019
Abstract: The aldol reaction is one of the most fundamental stereocontrolled carbon-carbon bond-forming reactions and is mainly catalyzed by aldolases in nature. Despite the fact that the aldol reaction has been widely proposed to be involved in fungal secondary metabolite biosynthesis, a dedicated aldolase that catalyzes stereoselective aldol reactions has only rarely been reported in fungi. Herein, we activated a cryptic polyketide biosynthetic gene cluster that was upregulated in the fungal wheat pathogen Parastagonospora nodorum during plant infection this resulted in the production of the phytotoxic stemphyloxin II (1). Through heterologous reconstruction of the biosynthetic pathway and in vitro assay by using cell-free lysate from Aspergillus nidulans, we demonstrated that a berberine bridge enzyme (BBE)-like protein SthB catalyzes an intramolecular aldol reaction to establish the bridged tricyclo[6.2.2.0
Heterologous expression of cytotoxic sesquiterpenoids from the medicinal mushroom Lignosus rhinocerotis in yeast
Publisher: Springer Science and Business Media LLC
Date: 12-06-2017
Identification of the Viridicatumtoxin and Griseofulvin Gene Clusters from Penicillium aethiopicum
Publisher: Elsevier BV
Date: 05-2010
Metabolic Engineering for the Production of Natural Products
Publisher: Annual Reviews
Date: 15-07-2011
DOI: 10.1146/ANNUREV-CHEMBIOENG-061010-114209
Abstract: Natural products and their derivatives play an important role in modern healthcare as frontline treatments for many diseases and as inspiration for chemically synthesized therapeutics. With advances in sequencing and recombinant DNA technology, many of the biosynthetic pathways responsible for the production of these chemically complex yet valuable compounds have been elucidated. With an ever-expanding toolkit of biosynthetic components, metabolic engineering is an increasingly powerful method to improve natural product titers and generate novel compounds. Heterologous production platforms have enabled access to pathways from difficult to culture strains, systems biology and metabolic modeling tools have resulted in increasing predictive and analytic capabilities, advances in expression systems and regulation have enabled the fine-tuning of pathways for increased efficiency, and characterization of in idual pathway components has facilitated the construction of hybrid pathways for the production of new compounds. These advances in the many aspects of metabolic engineering not only have yielded fascinating scientific discoveries but also make it an increasingly viable approach for the optimization of natural product biosynthesis.
The expanding CRISPR toolbox for natural product discovery and engineering in filamentous fungi
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D2NP00055E
Abstract: This review provides an overview of CRISPR/Cas-based strategies for biosynthetic gene cluster engineering in filamentous fungi.
CRISPR-mediated activation of biosynthetic gene clusters for bioactive molecule discovery in filamentous fungi
Publisher: Cold Spring Harbor Laboratory
Date: 14-01-2020
DOI: 10.1101/2020.01.12.903286
Abstract: Accessing the full biosynthetic potential encoded in the genomes of fungi is limited by the low expression of most biosynthetic gene clusters (BGCs) under common laboratory culture conditions. CRISPR-mediated transcriptional activation (CRISPRa) of fungal BGC could accelerate genomics-driven bioactive secondary metabolite discovery. In this work, we established the first CRISPRa system for filamentous fungi. First, we constructed a CRISPR/dLbCas12a-VPR-based system and demonstrated the activation of a fluorescent reporter in Aspergillus nidulans . Then, we targeted the native nonribosomal peptide synthetase-like (NRPS-like) gene micA in both chromosomal and episomal contexts, achieving increased production of the compound microperfuranone. Finally, multi-gene CRISPRa led to the discovery of the mic cluster product as dehydromicroperfuranone. Additionally, we demonstrated the utility of the variant dLbCas12a D156R -VPR for CRISPRa at room temperature culture conditions. Different aspects that influence the efficiency of CRISPRa in fungi were investigated, providing a framework for the further development of fungal artificial transcription factors based on CRISPR/Cas.
Functional genomics-guided discovery of a light-activated phytotoxin in the wheat pathogen Parastagonospora nodorum via pathway activation
Publisher: Wiley
Date: 10-04-2017
Abstract: Parastagonospora nodorum is an important pathogen of wheat. The contribution of secondary metabolites to this pathosystem is poorly understood. A biosynthetic gene cluster (SNOG_08608-08616) has been shown to be upregulated during the late stage of P. nodorum wheat leaf infection. The gene cluster shares several homologues with the Cercospora nicotianae CTB gene cluster encoding the biosynthesis of cercosporin. Activation of the gene cluster by overexpression (OE) of the transcription factor gene (SNOG_08609) in P. nodorum resulted in the production of elsinochrome C, a perelyenequinone phytotoxin structurally similar to cercosporin. Heterologous expression of the polyketide synthase gene elcA from the gene cluster in Aspergillus nidulans resulted in the production of the polyketide precursor nortoralactone common to the cercosporin pathway. Elsinochrome C could be detected on wheat leaves infected with P. nodorum, but not in the elcA disruption mutant. The compound was shown to exhibit necrotic activity on wheat leaves in a light-dependent manner. Wheat seedling infection assays showed that ΔelcA exhibited reduced virulence compared with wild type, while infection by an OE strain overproducing elsinochrome C resulted in larger lesions on leaves. These data provided evidence that elsinochrome C contributes to the virulence of P. nodorum against wheat.
Aspergillus hancockii sp. nov., a biosynthetically talented fungus endemic to southeastern Australian soils
Publisher: Public Library of Science (PLoS)
Date: 05-04-2017
Involvement of Lipocalin-like CghA in Decalin-Forming Stereoselective Intramolecular [4+2] Cycloaddition
Publisher: Wiley
Date: 02-10-2015
Characterization of the Suillus grevillei Quinone Synthetase GreA Supports a Nonribosomal Code for Aromatic α-Keto Acids
Publisher: Wiley
Date: 22-06-2012
Abstract: The gene greA was cloned from the genome of the basidiomycete Suillus grevillei. It encodes a monomodular natural product biosynthesis protein composed of three domains for adenylation, thiolation, and thioesterase and, hence, is reminiscent of a nonribosomal peptide synthetase (NRPS). GreA was biochemically characterized in vitro. It was identified as atromentin synthetase and therefore represents one of only a limited number of biochemically characterized NRPS-like enzymes which accept an aromatic α-keto acid. Specificity-conferring amino acid residues--collectively referred to as the nonribosomal code--were predicted for the primary sequence of the GreA adenylation domain and were an unprecedented combination for aromatic α-keto acids. Plausible support for this new code came from in silico simulation of the adenylation domain structure. According to the model, the predicted residues line the active site and, therefore, very likely contribute to substrate specificity.
Cognitive–behavioural therapy for a variety of conditions: an overview of systematic reviews and panoramic meta-analysis
Publisher: National Institute for Health and Care Research
Date: 02-2021
DOI: 10.3310/HTA25090
Abstract: Cognitive–behavioural therapy aims to increase quality of life by changing cognitive and behavioural factors that maintain problematic symptoms. A previous overview of cognitive–behavioural therapy systematic reviews suggested that cognitive–behavioural therapy was effective for many conditions. However, few of the included reviews synthesised randomised controlled trials. This project was undertaken to map the quality and gaps in the cognitive–behavioural therapy systematic review of randomised controlled trial evidence base. Panoramic meta-analyses were also conducted to identify any across-condition general effects of cognitive–behavioural therapy. The overview was designed with cognitive–behavioural therapy patients, clinicians and researchers. The Cochrane Library, MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Child Development & Adolescent Studies, Database of Abstracts of Reviews of Effects and OpenGrey databases were searched from 1992 to January 2019. Study inclusion criteria were as follows: (1) fulfil the Centre for Reviews and Dissemination criteria (2) intervention reported as cognitive–behavioural therapy or including one cognitive and one behavioural element (3) include a synthesis of cognitive–behavioural therapy trials (4) include either health-related quality of life, depression, anxiety or pain outcome and (5) available in English. Review quality was assessed with A MeaSurement Tool to Assess systematic Reviews (AMSTAR)-2. Reviews were quality assessed and data were extracted in duplicate by two independent researchers, and then mapped according to condition, population, context and quality. The effects from high-quality reviews were pooled within condition groups, using a random-effect panoramic meta-analysis. If the across-condition heterogeneity was I 2 75%, we pooled across conditions. Subgroup analyses were conducted for age, delivery format, comparator type and length of follow-up, and a sensitivity analysis was performed for quality. A total of 494 reviews were mapped, representing 68% (27/40) of the categories of the International Classification of Diseases, Eleventh Revision, Mortality and Morbidity Statistics. Most reviews (71%, 351/494) were of lower quality. Research on older adults, using cognitive–behavioural therapy preventatively, ethnic minorities and people living outside Europe, North America or Australasia was limited. Out of 494 reviews, 71 were included in the primary panoramic meta-analyses. A modest effect was found in favour of cognitive–behavioural therapy for health-related quality of life (standardised mean difference 0.23, 95% confidence interval 0.05 to 0.41, prediction interval –0.05 to 0.50, I 2 = 32%), anxiety (standardised mean difference 0.30, 95% confidence interval 0.18 to 0.43, prediction interval –0.28 to 0.88, I 2 = 62%) and pain (standardised mean difference 0.23, 95% confidence interval 0.05 to 0.41, prediction interval –0.28 to 0.74, I 2 = 64%) outcomes. All condition, subgroup and sensitivity effect estimates remained consistent with the general effect. A statistically significant interaction effect was evident between the active and non-active comparator groups for the health-related quality-of-life outcome. A general effect for depression outcomes was not produced as a result of considerable heterogeneity across reviews and conditions. Data extraction and analysis were conducted at the review level, rather than returning to the in idual trial data. This meant that the risk of bias of the in idual trials could not be accounted for, but only the quality of the systematic reviews that synthesised them. Owing to the consistency and homogeneity of the highest-quality evidence, it is proposed that cognitive–behavioural therapy can produce a modest general, across-condition benefit in health-related quality-of-life, anxiety and pain outcomes. Future research should focus on how the modest effect sizes seen with cognitive–behavioural therapy can be increased, for ex le identifying alternative delivery formats to increase adherence and reduce dropout, and pursuing novel methods to assess intervention fidelity and quality. This study is registered as PROSPERO CRD42017078690. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 25, No. 9. See the NIHR Journals Library website for further project information.
The genome of the Tiger Milk mushroom, Lignosus rhinocerotis, provides insights into the genetic basis of its medicinal properties
Publisher: Springer Science and Business Media LLC
Date: 2014
Synthaser: a CD-Search enabled Python toolkit for analysing domain architecture of fungal secondary metabolite megasynth(et)ases
Publisher: Springer Science and Business Media LLC
Date: 11-11-2021
DOI: 10.1186/S40694-021-00120-9
Abstract: Fungi are prolific producers of secondary metabolites (SMs), which are bioactive small molecules with important applications in medicine, agriculture and other industries. The backbones of a large proportion of fungal SMs are generated through the action of large, multi-domain megasynth(et)ases such as polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs). The structure of these backbones is determined by the domain architecture of the corresponding megasynth(et)ase, and thus accurate annotation and classification of these architectures is an important step in linking SMs to their biosynthetic origins in the genome. Here we report synthaser, a Python package leveraging the NCBI’s conserved domain search tool for remote prediction and classification of fungal megasynth(et)ase domain architectures. Synthaser is capable of batch sequence analysis, and produces rich textual output and interactive visualisations which allow for quick assessment of the megasynth(et)ase ersity of a fungal genome. Synthaser uses a hierarchical rule-based classification system, which can be extensively customised by the user through a web application ( gamcil.github.io/synthaser ). We show that synthaser provides more accurate domain architecture predictions than comparable tools which rely on curated profile hidden Markov model (pHMM)-based approaches the utilisation of the NCBI conserved domain database also allows for significantly greater flexibility compared to pHMM approaches. In addition, we demonstrate how synthaser can be applied to large scale genome mining pipelines through the construction of an Aspergillus PKS similarity network. Synthaser is an easy to use tool that represents a significant upgrade to previous domain architecture analysis tools. It is freely available under a MIT license from PyPI ( roject/synthaser ) and GitHub ( amcil/synthaser ).
SnPKS19 encodes the polyketide synthase for alternariol mycotoxin biosynthesis in the wheat pathogen Parastagonospora nodorum
Publisher: American Society for Microbiology
Date: 15-08-2015
DOI: 10.1128/AEM.00278-15
Abstract: Alternariol (AOH) is an important mycotoxin from the Alternaria fungi. AOH was detected for the first time in the wheat pathogen Parastagonospora nodorum in a recent study. Here, we exploited reverse genetics to demonstrate that SNOG_15829 ( SnPKS19 ), a close homolog of Penicillium aethiopicum norlichexanthone (NLX) synthase gene gsfA , is required for AOH production. We further validate that SnPKS19 is solely responsible for AOH production by heterologous expression in Aspergillus nidulans . The expression profile of SnPKS19 based on previous P. nodorum microarray data correlated with the presence of AOH in vitro and its absence in planta . Subsequent characterization of the Δ SnPKS19 mutants showed that SnPKS19 and AOH are not involved in virulence and oxidative stress tolerance. Identification and characterization of the P. nodorum SnPKS19 cast light on a possible alternative AOH synthase gene in Alternaria alternata and allowed us to survey the distribution of AOH synthase genes in other fungal genomes. We further demonstrate that phylogenetic analysis could be used to differentiate between AOH synthases and the closely related NLX synthases. This study provides the basis for studying the genetic regulation of AOH production and for development of molecular diagnostic methods for detecting AOH-producing fungi in the future.
Priorities for research on neuromodulatory subcortical systems in Alzheimer's disease: Position paper from the NSS PIA of ISTAART
Publisher: Wiley
Date: 15-01-2023
DOI: 10.1002/ALZ.12937
Abstract: The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau‐associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction and cortical lesions. Accumulating evidence supports the role of NSS dysfunction and degeneration in the behavioral and neuropsychiatric manifestations featured early in AD. Experimental studies even suggest that AD‐associated NSS degeneration drives brain neuroinflammatory status and contributes to disease progression, including the exacerbation of cortical lesions. Given the important pathophysiologic and etiologic roles that involve the NSS in early AD stages, there is an urgent need to expand our understanding of the mechanisms underlying NSS vulnerability and more precisely detail the clinical progression of NSS changes in AD. Here, the NSS Professional Interest Area of the International Society to Advance Alzheimer's Research and Treatment highlights knowledge gaps about NSS within AD and provides recommendations for priorities specific to clinical research, biomarker development, modeling, and intervention. Neuromodulatory nuclei degenerate in early Alzheimer's disease pathological stages. Alzheimer's pathophysiology is exacerbated by neuromodulatory nuclei degeneration. Neuromodulatory nuclei degeneration drives neuropsychiatric symptoms in dementia. Biomarkers of neuromodulatory integrity would be value‐creating for dementia care. Neuromodulatory nuclei present strategic prospects for disease‐modifying therapies.
Noradrenergic Add-on Therapy with Extended-Release Guanfacine in Alzheimer's Disease (NorAD): study protocol for a randomised clinical trial and COVID-19 amendments
Publisher: Springer Science and Business Media LLC
Date: 08-2022
DOI: 10.1186/S13063-022-06190-3
Abstract: Guanfacine is a α2A adrenergic receptor agonist approved for treating attention deficit hyperactivity disorder (ADHD). It is thought to act via postsynaptic receptors in the prefrontal cortex, modulating executive functions including the regulation of attention. Attention is affected early in Alzheimer’s disease (AD), and this may relate to pathological changes within the locus coeruleus, the main source of noradrenergic pathways within the brain. Given that cholinergic pathways, also involved in attention, are disrupted in AD, the combination of noradrenergic and cholinergic treatments may have a synergistic effect on symptomatic AD. The primary objective of the NorAD trial is to evaluate the change in cognition with 12 weeks of treatment of extended-release guanfacine (GXR) against a placebo as a combination therapy with cholinesterase inhibitors in participants with mild to moderate Alzheimer’s disease. NorAD is a 3-month, single-centre, randomised, double-blind, placebo-controlled, phase III trial of extended-release guanfacine (GXR) in participants with mild to moderate Alzheimer’s disease. A total of 160 participants will be randomised to receive either daily guanfacine or placebo in combination with approved cholinesterase treatment for 12 weeks. The primary outcome is the change in cognition, as measured by the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), from baseline to follow-up in the treatment group compared to the placebo group. Secondary outcomes include the change in additional cognitive measures of attention (Tests of Attention: Trails A and B, digit-symbol substitution, Test of Everyday Attention and CANTAB-RVP), neuropsychiatric symptoms (Neuropsychiatric Inventory), caregiver burden (Zarit Burden Interview) and activities of daily living (Alzheimer’s Disease Co-operative Study – Activities of Daily Living Inventory). From July 2020, observation of change following cessation of treatment is also being assessed. There is strong evidence for early noradrenergic dysfunction in Alzheimer’s disease. The NorAD trial aims to determine whether guanfacine, a noradrenergic alpha-2 agonist, improves attention and cognition when used in addition to standard cholinergic treatment. ClinicalTrials.gov NCT03116126 . Registered on 14 April 2017 EudraCT: 2016-002598-36
A chemical ecogenomics approach to understand the roles of secondary metabolites in fungal cereal pathogens
Publisher: Frontiers Media SA
Date: 19-11-2014
Characterisation and heterologous biosynthesis of burnettiene A, a new polyene-decalin polyketide from Aspergillus burnettii
Publisher: Cambridge University Press (CUP)
Date: 07-09-2021
DOI: 10.33774/CHEMRXIV-2021-P016T
Abstract: Chemical exploration of the recently described Australian fungus, Aspergillus burnettii, uncovered a new metabolite, burnettiene A. Here, we characterise the structure of burnettiene A as a polyene-decalin polyketide. Bioinformatic analysis of the genome of A. burnettii identified a putative biosynthetic gene cluster for burnettiene A (bue), consisting of eight genes and sharing similarity to the fusarielin gene cluster. Introduction of the reassembled bue gene cluster into Aspergillus nidulans for heterologous expression resulted in the production of burnettiene A under native promoters. Omission of bueE encoding a cytochrome P450 led to the production of preburnettiene A, confirming that BueE is responsible for catalysing the regiospecific multi-oxidation of terminal methyl groups to carboxylic acids. Similarly, bueF was shown to encode an ester-forming methyltransferase, with its omission resulting in the production of the tricarboxylic acid, preburnettiene B. Introduction of an additional copy of the transcription factor bueR under the regulation of the gpdA promoter significantly improved the heterologous production of the burnettienes. Burnettiene A displayed strong in vitro cytotoxicity against mouse myeloma NS-1 cells (MIC 0.8 µg/mL).
Genetic characterization of enzymes involved in the priming steps of oxytetracycline biosynthesis in Streptomyces rimosus
Publisher: Microbiology Society
Date: 08-2011
Abstract: Tetracyclines are clinically important aromatic polyketides whose biosynthesis is catalysed by bacterial type II polyketide synthases (PKSs). Tetracyclines are biosynthesized starting with an amide-containing malonamate starter unit and the resulting C-2 carboxyamide is critical for the antibiotic activities. In this work, we genetically verified that an amidotransferase, OxyD, and a thiolase, OxyP, are involved in the biosynthesis and incorporation of the starter unit. First, two mutations, R248T and D268N, were found to be present in OxyD* encoded in Streptomyces rimosus ATCC 13224, a strain that produces the acetate-primed 2-acetyl-2-decarboxyamido-oxytetracycline (ADOTC) instead of the malonamate-primed oxytetracycline (OTC). Homology modelling suggested that in particular D268N may inactivate OxyD. Complementation of S. rimosus ATCC 13224 with wild-type OxyD restored OTC biosynthesis, thereby confirming the essential role of OxyD in the synthesis of the amide starter unit. Second, using a series of knockout and complementation approaches, we demonstrated that OxyP is most likely involved in maintaining fidelity of the amide-priming process via hydrolysis of the competing acetate priming starter units. While the inactivation of OxyP does not eliminate OTC biosynthesis, the ratio of acetate-primed ADOTC to malonamate-primed OTC is significantly increased. This suggests that OxyP plays an ancillary role in OTC biosynthesis and is important for minimizing the levels of ADOTC, a shunt product that has much weaker antibiotic activities than OTC.
The Fumagillin Biosynthetic Gene Cluster in Aspergillus fumigatus Encodes a Cryptic Terpene Cyclase Involved in the Formation of β-trans-Bergamotene
Publisher: American Chemical Society (ACS)
Date: 19-03-2013
DOI: 10.1021/JA312503Y
Hancockiamides: phenylpropanoid piperazines from Aspergillus hancockii are biosynthesised by a versatile dual single-module NRPS pathway
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D0OB02243H
Abstract: The hancockiamides are an unusual new family of N -cinnamoylated piperazines from the Australian soil fungus Aspergillus hancockii , originating from mixed nonribosomal peptide and phenylpropanoid pathways.
Genomics-Driven Discovery of Phytotoxic Cytochalasans Involved in the Virulence of the Wheat Pathogen Parastagonospora nodorum
Publisher: American Chemical Society (ACS)
Date: 09-12-2020
DOI: 10.1021/ACSCHEMBIO.9B00791
Abstract: The etiology of fungal pathogenesis of grains is critical to global food security. The large number of orphan biosynthetic gene clusters uncovered in fungal plant pathogen genome sequencing projects suggests that we have a significant knowledge gap about the secondary metabolite repertoires of these pathogens and their roles in plant pathogenesis. Cytochalasans are a family of natural products of significant interest due to their ability to bind to actin and interfere with cellular processes that involved actin polymerization however, our understanding of their biosynthesis and biological roles remains incomplete. Here, we identified a putative polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) gene cluster (
Resorculins: hybrid polyketide macrolides from Streptomyces sp. MST-91080
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D2OB02332F
Abstract: The discovery of the resoruclins, new 3,5-dihydroxybenzoic acid containing macrolides for Steptomyces sp. MST-91080, and their putative biosynthetic pathway.
Heterologous biosynthesis of elsinochrome A sheds light on the formation of the photosensitive perylenequinone system
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C8SC02870B
Abstract: Formation of the three C–C bridges between the two naphthol monomers for elsinochrome ( 1 ) involves three distinct classes of oxidases.
Stereodivergent Hydroxylation of Berkeleylactones by Penicillium turbatum
Publisher: American Chemical Society (ACS)
Date: 16-12-2023
Discovery and Characterization of a Group of Fungal Polycyclic Polyketide Prenyltransferases
Publisher: American Chemical Society (ACS)
Date: 25-05-2012
DOI: 10.1021/JA3028636
Discovery and Heterologous Biosynthesis of the Burnettramic Acids: Rare PKS-NRPS-Derived Bolaamphiphilic Pyrrolizidinediones from an Australian Fungus, Aspergillus burnettii
Publisher: American Chemical Society (ACS)
Date: 08-02-2019
DOI: 10.1021/ACS.ORGLETT.8B04042
Abstract: The burnettramic acids are a new class of antibiotics from an Australian fungus Aspergillus burnettii. The rare bola hiphilic scaffold consists of β-d-mannose linked to a pyrrolizidinedione unit via a 26-carbon chain. The most abundant metabolite displayed potent in vitro antifungal activity. Comparative genomics identified the hybrid PKS-NRPS bua gene cluster, which was verified by heterologous pathway reconstitution in Aspergillus nidulans.
Epigenetic Genome Mining of an Endophytic Fungus Leads to the Pleiotropic Biosynthesis of Natural Products
Publisher: Wiley
Date: 27-05-2015
Next-generation sequencing approach for connecting secondary metabolites to biosynthetic gene clusters in fungi
Publisher: Frontiers Media SA
Date: 14-01-2015
Three Recently Diverging Duplicated Methyltransferases Exhibit Substrate-Dependent Regioselectivity Essential for Xantholipin Biosynthesis
Publisher: American Chemical Society (ACS)
Date: 10-07-2020
The impact of assistive technology on burden and psychological well‐being in informal caregivers of people with dementia (ATTILA Study)
Publisher: Wiley
Date: 2020
DOI: 10.1002/TRC2.12064
Abstract: Assistive technology and telecare (ATT) may alleviate psychological burden in informal caregivers of people with dementia. This study assessed the impact of ATT on informal caregivers’ burden and psychological well‐being. In iduals with dementia and their informal caregivers were recruited to a randomized‐controlled trial assessing effectiveness of ATT. Caregivers were allocated to two groups according to their cared‐for person's randomization to a full or basic package of ATT and were assessed on caregiver burden, state anxiety, and depression. Caregivers’ data from three assessments over 6 months of the trial were analyzed. No significant between‐ or within‐group differences at any time point on caregivers’ burden, anxiety, and depression levels were found. Full ATT for people with dementia did not impact caregivers’ psychological outcomes compared to basic ATT. The length of follow up was restricted to 6 months.
Intra-hemocoel injection of pseurotin A from Metarhizium anisopliae, induces dose-dependent reversible paralysis in the Greater Wax Moth (Galleria mellonella)
Publisher: Elsevier BV
Date: 04-2022
DOI: 10.1016/J.FGB.2022.103675
Abstract: Species from the Metarhizium genus are the causal agents of the green muscardine disease of insects. These fungi have been successfully employed for the biological control of pests over decades. Besides the biocontrol applications, recent efforts for genome sequencing of species in this genus have revealed a great ersity of biosynthetic gene clusters potentially associated with secondary metabolite synthesis. Amongst such potential molecules are the pseurotins, compounds with several activities, as chitin synthase inhibitors, and immunoglobulin E suppressors. Here, we report, for the first time, the isolation of pseurotin A from the culture broth of M. anisopliae, as well as the characterization of the effects of this compound over the model-arthropod Galleria mellonella. Pseurotin A displayed dose-dependent reversible paralysis effects when injected into the larvae hemocoel. However, the posterior challenge of the treated insects with M. anisopliae conidia did not lead to increased mortality, suggesting that pseurotin A treatment did not increase larvae susceptibility to the green muscardine disease. Although apparent insecticidal effects were not observed for pseurotin A, the paralysis effect observed can be important in M. anisopliae infection development.
A retrospective study on the combined biomarkers and ratios in serum and pleural fluid to distinguish the multiple types of pleural effusion
Publisher: Springer Science and Business Media LLC
Date: 19-03-2021
DOI: 10.1186/S12890-021-01459-W
Abstract: Pleural effusion (PE) is a common clinical manifestation, and millions of people suffer from pleural disease. Herein, this retrospective study was performed to evaluate the biomarkers and ratios in serum and pleural fluid (PF) for the differential diagnosis of the multiple types of PE and search for a new diagnostic strategy for PE. In-patients, who developed tuberculous PE (TPE), malignant PE (MPE), complicated parapneumonic effusion (CPPE), uncomplicated PPE (UPPE), or PE caused by connective tissue diseases (CTDs) and underwent thoracentesis at Peking University People’s Hospital from November 2016 to April 2019, were included in this study. Eleven biomarkers and their ratios in serum and PF were investigated and compared between pairs of the different PE groups, and a decision-tree was developed. Totally 112 PE cases, including 25 MPE, 33 TPE, 19 CPPE, 27 UPPE, and 8 PE caused by CTDs, were reviewed. Biomarkers and ratios showed good diagnostic performance with high area under the curve values, sensitivities, and specificities for the differential diagnosis of the multiple types of PE. According to the decision-tree analysis, the combination of adenosine deaminase (ADA), serum albumin, serum lactate dehydrogenase, total protein, PF-LDH/ADA, and PF-LDH/TP provided the best predictive capacity with an overall accuracy of 84.8% the sensitivity and specificity for TPE diagnosis were 100% and 98.7%, respectively. The biomarkers and ratios showed good diagnostic performance, and a decision-tree with an overall accuracy of 84.8% was developed to differentiate the five types of PE in clinical settings.
clinker & clustermap.js: Automatic generation of gene cluster comparison figures
Publisher: Cold Spring Harbor Laboratory
Date: 09-11-2020
DOI: 10.1101/2020.11.08.370650
Abstract: Genes involved in biological pathways are often collocalised in gene clusters, the comparison of which can give valuable insights into their function and evolutionary history. However, comparison and visualisation of gene cluster homology is a tedious process, particularly when many clusters are being compared. Here, we present clinker , a Python based tool, and clustermap.js , a companion JavaScript visualisation library, which used together can automatically generate accurate, interactive, publication-quality gene cluster comparison figures directly from sequence files. Source code and documentation for clinker and clustermap.js is available on GitHub ( amcil/clinker and amcil/clustermap.js , respectively) under the MIT license. clinker can be installed directly from the Python Package Index via pip . E-mail: cameron.gilchrist@research.uwa.edu.au , yitheng.chooi@uwa.edu.au
Noradrenergic-dependent functions are associated with age-related locus coeruleus signal intensity differences
Publisher: Springer Science and Business Media LLC
Date: 06-04-2020
DOI: 10.1038/S41467-020-15410-W
Abstract: The locus coeruleus (LC), the origin of noradrenergic modulation of cognitive and behavioral function, may play an important role healthy ageing and in neurodegenerative conditions. We investigated the functional significance of age-related differences in mean normalized LC signal intensity values (LC-CR) in magnetization-transfer (MT) images from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) cohort - an open-access, population-based dataset. Using structural equation modelling, we tested the pre-registered hypothesis that putatively noradrenergic (NA)-dependent functions would be more strongly associated with LC-CR in older versus younger adults. A unidimensional model (within which LC-CR related to a single factor representing all cognitive and behavioral measures) was a better fit with the data than the a priori two-factor model (within which LC-CR related to separate NA-dependent and NA-independent factors). Our findings support the concept that age-related reduction of LC structural integrity is associated with impaired cognitive and behavioral function.
Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis
Publisher: Beilstein Institut
Date: 05-11-2019
DOI: 10.3762/BJOC.15.256
Abstract: Chemical investigation of an undescribed Australian fungus, Aspergillus nanangensis , led to the identification of the nanangenines – a family of seven new and three previously reported drimane sesquiterpenoids. The structures of the nanangenines were elucidated by detailed spectroscopic analysis supported by single crystal X-ray diffraction studies. The compounds were assayed for in vitro activity against bacteria, fungi, mammalian cells and plants. Bioinformatics analysis, including comparative analysis with other acyl drimenol-producing Aspergilli, led to the identification of a putative nanangenine biosynthetic gene cluster that corresponds to the proposed biosynthetic pathway for nanangenines.
Turonicin A, an Antifungal Linear Polyene Polyketide from an Australian Streptomyces sp.
Publisher: American Chemical Society (ACS)
Date: 08-2023
Cre/lox-mediated chromosomal integration of biosynthetic gene clusters for heterologous expression in Aspergillus nidulans
Publisher: Cold Spring Harbor Laboratory
Date: 20-08-2021
DOI: 10.1101/2021.08.20.457072
Abstract: Building strains of filamentous fungi for stable long-term heterologous expression of large biosynthetic pathways is limited by the low transformation efficiency or genetic stability of current methods. Here, we developed a system for targeted chromosomal integration of large biosynthetic gene clusters in Aspergillus nidulans based on site-specific recombinase-mediated cassette exchange. We built A. nidulans strains harboring a chromosomal landing pad for Cre/ lox -mediated recombination and demonstrated efficient targeted integration of a 21 kb DNA fragment in a single step. We further evaluated the integration at two loci by analyzing the expression of a fluorescent reporter and the production of a heterologous polyketide metabolite. We compared chromosomal expression at those landing loci to episomal AMA1-based expression, which also shed light on uncharacterized aspects of episomal expression in filamentous fungi. This is the first demonstration of site-specific recombinase-mediated integration in filamentous fungi, setting the foundations for the further development of this tool.
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