| 1. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 2. |
- Cerullo, Gabriella, et al.
(författare)
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The Synthetic Potential of Fungal Feruloyl Esterases: A Correlation with Current Classification Systems and Predicted Structural Properties
- 2018
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Ingår i: Catalysts. - : MDPI AG. - 2073-4344. ; 8:242
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Tidskriftsartikel (refereegranskat)abstract
- Twenty-eight fungal feruloyl esterases (FAEs) were evaluated for their synthetic abilities in a ternary system of n-hexane: t-butanol: 100 mM MOPS-NaOH pH 6.0 forming detergentless microemulsions. Five main derivatives were synthesized, namely prenyl ferulate, prenyl caffeate, butyl ferulate, glyceryl ferulate, and l-arabinose ferulate, offering, in general, higher yields when more hydrophilic alcohol substitutions were used. Acetyl xylan esterase-related FAEs belonging to phylogenetic subfamilies (SF) 5 and 6 showed increased synthetic yields among tested enzymes. In particular, it was shown that FAEs belonging to SF6 generally transesterified aliphatic alcohols more efficiently while SF5 members preferred bulkier l-arabinose. Predicted surface properties and structural characteristics were correlated with the synthetic potential of selected tannase-related, acetyl-xylan-related, and lipase-related FAEs (SF1-2, -6, -7 members) based on homology modeling and small molecular docking simulations.
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| 3. |
- Coconi Linares, Nancy, et al.
(författare)
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Recombinant production and characterization of six novel GH27 and GH36 α-galactosidases from Penicillium subrubescens and their synergism with a commercial mannanase during the hydrolysis of lignocellulosic biomass
- 2020
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Ingår i: Bioresource Technology. - : Elsevier BV. - 0960-8524. ; 295
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Tidskriftsartikel (refereegranskat)abstract
- α-Galactosidases are important industrial enzymes for hemicellulosic biomass degradation or modification. In this study, six novel extracellular α-galactosidases from Penicillium subrubescens were produced in Pichia pastoris and characterized. All α-galactosidases exhibited high affinity to pNPαGal, and only AglE was not active towards galacto-oligomers. Especially AglB and AglD released high amounts of galactose from guar gum, carob galactomannan and locust bean, but combining α-galactosidases with an endomannanase dramatically improved galactose release. Structural comparisons to other α-galactosidases and homology modelling showed high sequence similarities, albeit significant differences in mechanisms of productive binding, including discrimination between various galactosides. To our knowledge, this is the first study of such an extensive repertoire of extracellular fungal α-galactosidases, to demonstrate their potential for degradation of galactomannan-rich biomass. These findings contribute to understanding the differences within glycoside hydrolase families, to facilitate the development of new strategies to generate tailor-made enzymes for new industrial bioprocesses.
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| 4. |
- de Vries, Ronald P, et al.
(författare)
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Comparative genomics reveals high biological diversity and specific adaptations in the industrially and medically important fungal genus Aspergillus
- 2017
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe fungal genus Aspergillus is of critical importance to humankind. Species include those with industrial applications, important pathogens of humans, animals and crops, a source of potent carcinogenic contaminants of food, and an important genetic model. The genome sequences of eight aspergilli have already been explored to investigate aspects of fungal biology, raising questions about evolution and specialization within this genus.ResultsWe have generated genome sequences for ten novel, highly diverse Aspergillus species and compared these in detail to sister and more distant genera. Comparative studies of key aspects of fungal biology, including primary and secondary metabolism, stress response, biomass degradation, and signal transduction, revealed both conservation and diversity among the species. Observed genomic differences were validated with experimental studies. This revealed several highlights, such as the potential for sex in asexual species, organic acid production genes being a key feature of black aspergilli, alternative approaches for degrading plant biomass, and indications for the genetic basis of stress response. A genome-wide phylogenetic analysis demonstrated in detail the relationship of the newly genome sequenced species with other aspergilli.ConclusionsMany aspects of biological differences between fungal species cannot be explained by current knowledge obtained from genome sequences. The comparative genomics and experimental study, presented here, allows for the first time a genus-wide view of the biological diversity of the aspergilli and in many, but not all, cases linked genome differences to phenotype. Insights gained could be exploited for biotechnological and medical applications of fungi.
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| 5. |
- Klaubauf, Sylvia, 1981, et al.
(författare)
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Similar is not the same: Differences in the function of the (hemi-)cellulolytic regulator XlnR (Xlr1/Xyr1) in filamentous fungi
- 2014
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Ingår i: Fungal Genetics and Biology. - 1096-0937 .- 1087-1845. ; 72, s. 73-81
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Tidskriftsartikel (refereegranskat)abstract
- The transcriptional activator XlnR (Xlr1/Xyr1) is a major regulator in fungal xylan and cellulose degradation as well as in the utilization of d-xylose via the pentose catabolic pathway. XlnR homologs are commonly found in filamentous ascomycetes and often assumed to have the same function in different fungi. However, a comparison of the saprobe Aspergillus niger and the plant pathogen Magnaporthe oryzae showed different phenotypes for deletion strains of XlnR. In this study wild type and xlnR/xlr1/xyr1 mutants of five fungi were compared: Fusarium graminearum, M. oryzae, Trichoderma reesei, A. niger and Aspergillus nidulans. Growth profiling on relevant substrates and a detailed analysis of the secretome as well as extracellular enzyme activities demonstrated a common role of this regulator in activating genes encoding the main xylanolytic enzymes. However, large differences were found in the set of genes that is controlled by XlnR in the different species, resulting in the production of different extracellular enzyme spectra by these fungi. This comparison emphasizes the functional diversity of a fine-tuned (hemi-)cellulolytic regulatory system in filamentous fungi, which might be related to the adaptation of fungi to their specific biotopes. Data are available via ProteomeXchange with identifier PXD001190.
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| 6. |
- Krishnaswamyreddy, Sumitha, et al.
(författare)
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Phylogenetic analysis and substrate specificity of GH2 β-mannosidases from Aspergillus species.
- 2013
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Ingår i: FEBS Letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 587:21, s. 3444-3449
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Tidskriftsartikel (refereegranskat)abstract
- Phylogenetic analysis of glycoside hydrolase family 2 including Aspergillus sequences and characterised β-mannosidases from other organisms, clusters putative Aspergillus β-mannosidases in two distinct clades (A and B). Aspergillus species have at least one paralog in each of the two clades. It appears that clade A members are extracellular and clade B members intracellular. Substrate specificity analysis of MndA of Aspergillus niger (clade A) and MndB of Aspergillus nidulans (clade B) show that MndB, in contrast to MndA, does not hydrolyse polymeric mannan and has probably evolved to hydrolyse small unbranched β-mannosides like mannobiose. A 3D-model of MndB provides further insight.
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| 7. |
- Marinovíc, Mila, et al.
(författare)
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Comparative Analysis of Enzyme Production Patterns of Lignocellulose Degradation of Two White Rot Fungi : Obba rivulosa and Gelatoporia subvermispora
- 2022
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Ingår i: Biomolecules. - : MDPI. - 2218-273X. ; 12:8
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Tidskriftsartikel (refereegranskat)abstract
- The unique ability of basidiomycete white rot fungi to degrade all components of plant cell walls makes them indispensable organisms in the global carbon cycle. In this study, we analyzed the proteomes of two closely related white rot fungi, Obba rivulosa and Gelatoporia subvermispora, during eight-week cultivation on solid spruce wood. Plant cell wall degrading carbohydrate-active enzymes (CAZymes) represented approximately 5% of the total proteins in both species. A core set of orthologous plant cell wall degrading CAZymes was shared between these species on spruce suggesting a conserved plant biomass degradation approach in this clade of basidiomycete fungi. However, differences in time-dependent production of plant cell wall degrading enzymes may be due to differences among initial growth rates of these species on solid spruce wood. The obtained results provide insight into specific enzymes and enzyme sets that are produced during the degradation of solid spruce wood in these fungi. These findings expand the knowledge on enzyme production in nature-mimicking conditions and may contribute to the exploitation of white rot fungi and their enzymes for biotechnological applications.
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| 8. |
- Peciulyte, Ausra, 1986, et al.
(författare)
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Strategic screening of filamentous fungi for their production of lignocellulose degrading enzymes
- 2014
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Ingår i: 12th European Conference on Fungal Genetics (ECFG12) book of abstracts.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Filamentous fungi possess a high unexplored potential for production of lignocellulose degrading enzymes. There are a few fungi, such as Trichoderma reesei and Aspergillus niger, which are widely used in industry. But there is a huge interest in discovery of novel and more efficient enzymes, and therefore other fungi should be evaluated. The goal of this study was to strategically screen selected filamentous fungi, which are potentially good producers of lignocellulose degrading enzymes, and to link their genomic information to the experimental data.We picked 9 fungi for which genomic data is available and screened for their growth abilities on cellulose and lignocellulose (steam exploded spruce). The five best performing fungi were chosen for further cultivations for evaluation of their enzyme profiles and enzymatic hydrolysis efficiency. SDS-PAGE showed large differences between the secretomes of the different fungi. For enzyme screening different enzyme assays were designed based on the CAZymes in the genomes of these fungi and the characteristics of the growth substrates. Enzymes produced by the fungi were evaluated for their hydrolytic efficiency on the different substrates. All in all, our experimental approach provided insight into the mechanisms of enzymatic hydrolysis by different filamentous fungi.
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