scholarly journals Evolclust: automated inference of evolutionary conserved gene clusters in eukaryotes

2019 ◽  
Author(s):  
Marina Marcet-Houben ◽  
Toni Gabaldón
Keyword(s):  
Secondary Metabolism ◽  
Computational Prediction ◽  
Gene Clusters ◽  
Link Type ◽  
Automated Inference ◽  
Or Gene ◽  
Conserved Gene ◽  
Genome Comparisons

AbstractMotivationThe evolution and role of gene clusters in eukaryotes is poorly understood. Currently, most studies and computational prediction programs limit their focus to specific types of clusters, such as those involved in secondary metabolism.ResultsWe present Evolclust, a python-based tool for the inference of evolutionary conserved gene clusters from genome comparisons, independently of the function or gene composition of the cluster. Evolclust predicts conserved gene clusters from pairwise genome comparisons and infers families of related clusters from multiple (all vs all) genome comparisons.Availabilityhttps://github.com/Gabaldonlab/EvolClust/[email protected]

scholarly journals EvolClust: automated inference of evolutionary conserved gene clusters in eukaryotes

2019 ◽  
Author(s):  
Marina Marcet-Houben ◽  
Toni Gabaldón
Keyword(s):  
Secondary Metabolism ◽  
Computational Prediction ◽  
Gene Clusters ◽  
Supplementary Information ◽  
Supplementary Data ◽  
Automated Inference ◽  
Or Gene ◽  
Conserved Gene ◽  
Genome Comparisons

Abstract Motivation The evolution and role of gene clusters in eukaryotes is poorly understood. Currently, most studies and computational prediction programs limit their focus to specific types of clusters, such as those involved in secondary metabolism. Results We present EvolClust, a python-based tool for the inference of evolutionary conserved gene clusters from genome comparisons, independently of the function or gene composition of the cluster. EvolClust predicts conserved gene clusters from pairwise genome comparisons and infers families of related clusters from multiple (all versus all) genome comparisons. Availability and implementation https://github.com/Gabaldonlab/EvolClust/. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Legionellashows a diverse secondary metabolism dependent on a broad spectrum Sfp-type phosphopantetheinyl transferase

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2720 ◽  
Author(s):  
Nicholas J. Tobias ◽  
Tilman Ahrendt ◽  
Ursula Schell ◽  
Melissa Miltenberger ◽  
Hubert Hilbi ◽  
...  
Keyword(s):  
Secondary Metabolism ◽  
Communication Systems ◽  
Fatty Acid Biosynthesis ◽  
Cell Communication ◽  
Gene Clusters ◽  
Phosphopantetheinyl Transferase ◽  
Biosynthetic Gene Clusters ◽  
Legionnaires Disease ◽  
Huge Variety

Several members of the genusLegionellacause Legionnaires’ disease, a potentially debilitating form of pneumonia. Studies frequently focus on the abundant number of virulence factors present in this genus. However, what is often overlooked is the role of secondary metabolites fromLegionella. Following whole genome sequencing, we assembled and annotated theLegionella parisiensisDSM 19216 genome. Together with 14 other members of theLegionella, we performed comparative genomics and analysed the secondary metabolite potential of each strain. We found thatLegionellacontains a huge variety of biosynthetic gene clusters (BGCs) that are potentially making a significant number of novel natural products with undefined function. Surprisingly, only a single Sfp-like phosphopantetheinyl transferase is found in allLegionellastrains analyzed that might be responsible for the activation of all carrier proteins in primary (fatty acid biosynthesis) and secondary metabolism (polyketide and non-ribosomal peptide synthesis). Using conserved active site motifs, we predict some novel compounds that are probably involved in cell-cell communication, differing to known communication systems. We identify several gene clusters, which may represent novel signaling mechanisms and demonstrate the natural product potential ofLegionella.

scholarly journals Genome Wide Analysis Reveals the Role of VadA in Stress Response, Germination, and Sterigmatocystin Production in Aspergillus nidulans Conidia

2020 ◽  
Vol 8 (9) ◽  
pp. 1319 ◽  
Author(s):  
Ye-Eun Son ◽  
Hee-Soo Park
Keyword(s):  
Stress Response ◽  
Secondary Metabolism ◽  
Aspergillus Nidulans ◽  
Gene Clusters ◽  
Tube Formation ◽  
Spore Viability ◽  
Genetic Changes ◽  
Genome Wide ◽  
Trehalose Biosynthesis

In the Aspergillus species, conidia are asexual spores that are infectious particles responsible for propagation. Conidia contain various mycotoxins that can have detrimental effects in humans. Previous study demonstrated that VadA is required for fungal development and spore viability in the model fungus Aspergillus nidulans. In the present study, vadA transcriptomic analysis revealed that VadA affects the mRNA expression of a variety of genes in A. nidulans conidia. The genes that were primarily affected in conidia were associated with trehalose biosynthesis, cell-wall integrity, stress response, and secondary metabolism. Genetic changes caused by deletion of vadA were related to phenotypes of the vadA deletion mutant conidia. The deletion of vadA resulted in increased conidial sensitivity against ultraviolet stress and induced germ tube formation in the presence and absence of glucose. In addition, most genes in the secondary metabolism gene clusters of sterigmatocystin, asperfuranone, monodictyphenone, and asperthecin were upregulated in the mutant conidia with vadA deletion. The deletion of vadA led to an increase in the amount of sterigmatocystin in the conidia, suggesting that VadA is essential for the repression of sterigmatocystin production in conidia. These results suggest that VadA coordinates conidia maturation, stress response, and secondary metabolism in A. nidulans conidia.

scholarly journals The kinetochore protein Spc105, a novel interaction partner of LaeA, regulates development and secondary metabolism in Aspergillus flavus

2018 ◽  
Author(s):  
QingQing Zhi ◽  
Lei He ◽  
JieYing Li ◽  
Jing Li ◽  
ZhenLong Wang ◽  
...  
Keyword(s):  
Secondary Metabolism ◽  
Aspergillus Flavus ◽  
Leucine Zipper ◽  
Cyclopiazonic Acid ◽  
Gene Clusters ◽  
Interaction Partner ◽  
Kinetochore Protein ◽  
Metabolism Regulation ◽  
Fungal Secondary Metabolism

Nuclear protein LaeA is known as the global regulator of secondary metabolism in Aspergillus. LaeA connects with VeA and VelB to form a heterotrimeric complex, which coordinates fungal development and secondary metabolism. Here, we describe a new interaction partner of LaeA, the kinetochore protein Spc105, from the aflatoxin-producing fungus Aspergillus flavus. We showed that in addition to involvement in nuclear division, Spc105 is required for normal conidiophore development and sclerotia production of A. flavus. Moreover, Spc105 positively regulates the production of secondary metabolites such as aflatoxin and kojic acid, and negatively regulates the production of cyclopiazonic acid. Transcriptome analysis of the ?spc105 strain revealed that 23 backbone genes were differentially expressed, corresponding to 19 of the predicted 56 secondary metabolite gene clusters, suggesting a broad regulatory role of Spc105 in secondary metabolism. Notably, the reduced expression of laeA in our transcriptome data led to the discovery of the correlation between Spc105 and LaeA, and double mutant analysis indicated a functional interdependence between Spc105 and LaeA. Further, yeast two-hybrid (Y2H) and GST pull-down assays revealed that Spc105 interacts directly with the S-adenosylmethionine (SAM)-binding domain of LaeA, and that the leucine zipper motif in Spc105 is required for this interaction. The Spc105-LaeA interaction identified in our study indicates a cooperative interplay of distinct regulators in A. flavus, providing new insights into fungal secondary metabolism regulation networks.

scholarly journals Genetic Responses and Aflatoxin Inhibition during Co-Culture of Aflatoxigenic and Non-Aflatoxigenic Aspergillus flavus

Toxins ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 794
Author(s):  
Rebecca R. Sweany ◽  
Brian M. Mack ◽  
Geromy G. Moore ◽  
Matthew K. Gilbert ◽  
Jeffrey W. Cary ◽  
...  
Keyword(s):  
Gene Expression ◽  
Aspergillus Flavus ◽  
Gene Clusters ◽  
Aflatoxin Production ◽  
Acid Synthesis ◽  
Aflatoxin Contamination ◽  
Oxidation Reduction ◽  
Or Gene ◽  
Genetic Responses

Aflatoxin is a carcinogenic mycotoxin produced by Aspergillus flavus. Non-aflatoxigenic (Non-tox) A. flavus isolates are deployed in corn fields as biocontrol because they substantially reduce aflatoxin contamination via direct replacement and additionally via direct contact or touch with toxigenic (Tox) isolates and secretion of inhibitory/degradative chemicals. To understand touch inhibition, HPLC analysis and RNA sequencing examined aflatoxin production and gene expression of Non-tox isolate 17 and Tox isolate 53 mono-cultures and during their interaction in co-culture. Aflatoxin production was reduced by 99.7% in 72 h co-cultures. Fewer than expected unique reads were assigned to Tox 53 during co-culture, indicating its growth and/or gene expression was inhibited in response to Non-tox 17. Predicted secreted proteins and genes involved in oxidation/reduction were enriched in Non-tox 17 and co-cultures compared to Tox 53. Five secondary metabolite (SM) gene clusters and kojic acid synthesis genes were upregulated in Non-tox 17 compared to Tox 53 and a few were further upregulated in co-cultures in response to touch. These results suggest Non-tox strains can inhibit growth and aflatoxin gene cluster expression in Tox strains through touch. Additionally, upregulation of other SM genes and redox genes during the biocontrol interaction demonstrates a potential role of inhibitory SMs and antioxidants as additional biocontrol mechanisms and deserves further exploration to improve biocontrol formulations.

scholarly journals LaeA, a Regulator of Secondary Metabolism in Aspergillus spp

2004 ◽  
Vol 3 (2) ◽  
pp. 527-535 ◽  
Author(s):  
Jin Woo Bok ◽  
Nancy P. Keller
Keyword(s):  
Secondary Metabolism ◽  
Feedback Loop ◽  
Nuclear Protein ◽  
Gene Clusters ◽  
Product Formation ◽  
Primary Role ◽  
Wild Type ◽  
Global Regulator ◽  
Metabolic Gene

ABSTRACT Secondary metabolites, or biochemical indicators of fungal development, are of intense interest to humankind due to their pharmaceutical and/or toxic properties. We present here a novel Aspergillus nuclear protein, LaeA, as a global regulator of secondary metabolism in this genus. Deletion of laeA (ΔlaeA) blocks the expression of metabolic gene clusters, including the sterigmatocystin (carcinogen), penicillin (antibiotic), and lovastatin (antihypercholesterolemic agent) gene clusters. Conversely, overexpression of laeA triggers increased penicillin and lovastatin gene transcription and subsequent product formation. laeA expression is negatively regulated by AflR, a sterigmatocystin Zn2Cys6 transcription factor, in a unique feedback loop, as well as by two signal transduction elements, protein kinase A and RasA. Although these last two proteins also negatively regulate sporulation, ΔlaeA strains show little difference in spore production compared to the wild type, indicating that the primary role of LaeA is to regulate metabolic gene clusters.

scholarly journals Regulation of Secondary Metabolism by the Velvet Complex Is Temperature-Responsive in Aspergillus

2016 ◽  
Vol 6 (12) ◽  
pp. 4023-4033 ◽  
Author(s):  
Abigail L Lind ◽  
Timothy D Smith ◽  
Timothy Saterlee ◽  
Ana M Calvo ◽  
Antonis Rokas
Keyword(s):  
Gene Expression ◽  
Secondary Metabolism ◽  
Global Gene Expression ◽  
Gene Clusters ◽  
Temperature Dependent ◽  
Transcription Profiles ◽  
Fungal Secondary Metabolism ◽  
Opportunistic Human Pathogen ◽  
Velvet Complex

Abstract Sensing and responding to environmental cues is critical to the lifestyle of filamentous fungi. How environmental variation influences fungi to produce a wide diversity of ecologically important secondary metabolites (SMs) is not well understood. To address this question, we first examined changes in global gene expression of the opportunistic human pathogen, Aspergillus fumigatus, after exposure to different temperature conditions. We found that 11 of the 37 SM gene clusters in A. fumigatus were expressed at higher levels at 30° than at 37°. We next investigated the role of the light-responsive Velvet complex in environment-dependent gene expression by examining temperature-dependent transcription profiles in the absence of two key members of the Velvet protein complex, VeA and LaeA. We found that the 11 temperature-regulated SM gene clusters required VeA at 37° and LaeA at both 30 and 37° for wild-type levels of expression. Interestingly, four SM gene clusters were regulated by VeA at 37° but not at 30°, and two additional ones were regulated by VeA at both temperatures but were substantially less so at 30°, indicating that the role of VeA and, more generally of the Velvet complex, in the regulation of certain SM gene clusters is temperature-dependent. Our findings support the hypothesis that fungal secondary metabolism is regulated by an intertwined network of transcriptional regulators responsive to multiple environmental factors.

scholarly journals Comparative genome and transcriptome analyses revealing interspecies variations in the expression of fungal biosynthetic gene clusters

2020 ◽  
Author(s):  
Hiroki Takahashi ◽  
Maiko Umemura ◽  
Masaaki Shimizu ◽  
Akihiro Ninomiya ◽  
Yoko Kusuya ◽  
...  
Keyword(s):  
Secondary Metabolism ◽  
Filamentous Fungi ◽  
Bioactive Compounds ◽  
Expression Patterns ◽  
Gene Clusters ◽  
Transcriptional Level ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Fungal Secondary Metabolism ◽  
Conserved Gene

AbstractFilamentous fungi produce various bioactive compounds that are biosynthesized by a set of proteins encoded in biosynthetic gene clusters (BGCs). For an unknown reason, large parts of the BGCs are transcriptionally silent under laboratory conditions, which has hampered the discovery of novel fungal compounds. The transcriptional regulation of fungal secondary metabolism is not fully understood from an evolutionary viewpoint. To address this issue, we conducted comparative genomic and transcriptomic analyses using five closely related species of the Aspergillus section Fumigati: Aspergillus fumigatus, Aspergillus lentulus, Aspergillus udagawae, Aspergillus pseudoviridinutans, and Neosartorya fischeri. From their genomes, 298 secondary metabolite (SM) core genes were identified, with 27.4% to 41.5% being unique to a species. Compared with the species-specific genes, a set of section-conserved SM core genes was expressed at a higher rate and greater magnitude, suggesting that their expression tendency is correlated with the BGC distribution pattern. However, the section-conserved BGCs showed diverse expression patterns across the Fumigati species. Thus, not all common BGCs across species appear to be regulated in an identical manner. A consensus motif was sought in the promoter region of each gene in the 15 section-conserved BGCs among the Fumigati species. A conserved motif was detected in only two BGCs including the gli cluster. The comparative transcriptomic and in silico analyses provided insights into how the fungal SM gene cluster diversified at a transcriptional level, in addition to genomic rearrangements and cluster gains and losses. This information increases our understanding of the evolutionary processes associated with fungal secondary metabolism.Author summaryFilamentous fungi provide a wide variety of bioactive compounds that contribute to public health. The ability of filamentous fungi to produce bioactive compounds has been underestimated, and fungal resources can be developed into new drugs. However, most biosynthetic genes encoding bioactive compounds are not expressed under laboratory conditions, which hampers the use of fungi in drug discovery. The mechanisms underlying silent metabolite production are poorly understood. Here, we attempted to show the diversity in fungal transcriptional regulation from an evolutionary viewpoint. To meet this goal, the secondary metabolisms, at genomic and transcriptomic levels, of the most phylogenetically closely related species in Aspergillus section Fumigati were compared. The conserved biosynthetic gene clusters across five Aspergillus species were identified. The expression levels of the well-conserved gene clusters tended to be more active than the species-specific, which were not well-conserved, gene clusters. Despite highly conserved genetic properties across the species, the expression patterns of the well-conserved gene clusters were diverse. These findings suggest an evolutionary diversification at the transcriptional level, in addition to genomic rearrangements and gains and losses, of the biosynthetic gene clusters. This study provides a foundation for understanding fungal secondary metabolism and the potential to produce diverse fungal-based chemicals.

The Estimation of prostate specific antigen (PSA) concentrations in patients with prostatitis by fully automated ELISA technique.

2020 ◽  
Vol 3 (11) ◽  
pp. 1100-1104
Author(s):  
Hussein Naeem Aldhaheri ◽  
Ihsan Edan AlSaimary ◽  
Murtadha Mohammed ALMusafer
Keyword(s):  
Personal Information ◽  
Receptor Gene ◽  
Specific Antigen ◽  
Gene Clusters ◽  
Control Group ◽  
P Value ◽  
Group Data ◽  
Elisa Technique ◽  
And Control

      The Aim of this study was to determine Immunogenetic expression of  Toll-like receptor gene clusters related to prostatitis, to give acknowledge about Role of TLR in prostatitis immunity in men from Basrah and Maysan provinces. A case–control study included 135 confirmed prostatitis patients And 50 persons as a control group. Data about age, marital status, working, infertility, family history and personal information like (Infection, Allergy, Steroid therapy, Residency, Smoking, Alcohol Drinking, Blood group, Body max index (BMI) and the clinical finding for all patients of Prostatitis were collected. This study shows the effect of PSA level in patients with prostatitis and control group, with P-value <0.0001 therefore the study shows a positive significant between elevated PSA levels and Prostatitis.

scholarly journals Does intervention with GLP-1 receptor agonist semaglutide modulate perception of sweet taste in women with obesity: study protocol of a randomized, single-blinded, placebo-controlled clinical trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mojca Jensterle ◽  
Simona Ferjan ◽  
Tadej Battelino ◽  
Jernej Kovač ◽  
Saba Battelino ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Neural Response ◽  
Taste Perception ◽  
Taste Bud ◽  
Controlled Clinical Trial ◽  
Food Cues ◽  
Link Type ◽  
Visual Food Cues ◽  
Taste Bud Cells

Abstract Background Preclinical studies demonstrated that glucagon-like peptide 1 (GLP-1) is locally synthesized in taste bud cells and that GLP-1 receptor exists on the gustatory nerves in close proximity to GLP-1-containing taste bud cells. This local paracrine GLP-1 signalling seems to be specifically involved in the perception of sweets. However, the role of GLP-1 in taste perception remains largely unaddressed in clinical studies. Whether any weight-reducing effects of GLP-1 receptor agonists are mediated through the modulation of taste perception is currently unknown. Methods and analysis This is an investigator-initiated, randomized single-blind, placebo-controlled clinical trial. We will enrol 30 women with obesity and polycystic ovary syndrome (PCOS). Participants will be randomized in a 1:1 ratio to either semaglutide 1.0 mg or placebo for 16 weeks. The primary endpoints are alteration of transcriptomic profile of tongue tissue as changes in expression level from baseline to follow-up after 16 weeks of treatment, measured by RNA sequencing, and change in taste sensitivity as detected by chemical gustometry. Secondary endpoints include change in neural response to visual food cues and to sweet-tasting substances as assessed by functional MRI, change in body weight, change in fat mass and change in eating behaviour and food intake. Discussion This is the first study to investigate the role of semaglutide on taste perception, along with a neural response to visual food cues in reward processing regions. The study may identify the tongue and the taste perception as a novel target for GLP-1 receptor agonists. Ethics and disseminations The study has been approved by the Slovene National Medical Ethics Committee and will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Results will be submitted for publication in an international peer-reviewed scientific journal. Trial registration ClinicalTrials.govNCT04263415. Retrospectively registered on 10 February 2020

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