Genome sequencing and analysis of the versatile cell factory Aspergillus niger CBS 513.88
DSM1, Delft University of Technology2, University of Nottingham3, Technical University of Denmark4, Wageningen University and Research Centre5, University of Sheffield6, Utrecht University7, Biomax Informatics AG8, CLC bio9, University of Liverpool10, Ghent University11, University of Manchester12, University of Provence13, University of Groningen14, Pasteur Institute15, University of Amsterdam16, University of Angers17, Leiden University18, Radboud University Nijmegen19, University of Szeged20
TL;DR: The filamentous fungus Aspergillus niger is widely exploited by the fermentation industry for the production of enzymes and organic acids, particularly citric acid, and the sequenced genome revealed a large number of major facilitator superfamily transporters and fungal zinc binuclear cluster transcription factors.
Abstract: The filamentous fungus Aspergillus niger is widely exploited by the fermentation industry for the production of enzymes and organic acids, particularly citric acid. We sequenced the 33.9-megabase genome of A. niger CBS 513.88, the ancestor of currently used enzyme production strains. A high level of synteny was observed with other aspergilli sequenced. Strong function predictions were made for 6,506 of the 14,165 open reading frames identified. A detailed description of the components of the protein secretion pathway was made and striking differences in the hydrolytic enzyme spectra of aspergilli were observed. A reconstructed metabolic network comprising 1,069 unique reactions illustrates the versatile metabolism of A. niger. Noteworthy is the large number of major facilitator superfamily transporters and fungal zinc binuclear cluster transcription factors, and the presence of putative gene clusters for fumonisin and ochratoxin A synthesis.
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University of New Mexico1, Los Alamos National Laboratory2, Novozymes3, University of Provence4, VTT Technical Research Centre of Finland5, Pacific Northwest National Laboratory6, Joint Genome Institute7, United States Department of Agriculture8, Vienna University of Technology9, Pontifical Catholic University of Chile10, Oregon State University11, Genencor12
TL;DR: This work assembled 89 scaffolds to generate 34 Mbp of nearly contiguous T. reesei genome sequence comprising 9,129 predicted gene models, providing a roadmap for constructing enhanced T.Reesei strains for industrial applications such as biofuel production.
Abstract: Trichoderma reesei is the main industrial source of cellulases and hemicellulases used to depolymerize biomass to simple sugars that are converted to chemical intermediates and biofuels, such as ethanol. We assembled 89 scaffolds (sets of ordered and oriented contigs) to generate 34 Mbp of nearly contiguous T. reesei genome sequence comprising 9,129 predicted gene models. Unexpectedly, considering the industrial utility and effectiveness of the carbohydrate-active enzymes of T. reesei, its genome encodes fewer cellulases and hemicellulases than any other sequenced fungus able to hydrolyze plant cell wall polysaccharides. Many T. reesei genes encoding carbohydrate-active enzymes are distributed nonrandomly in clusters that lie between regions of synteny with other Sordariomycetes. Numerous genes encoding biosynthetic pathways for secondary metabolites may promote survival of T. reesei in its competitive soil habitat, but genome analysis provided little mechanistic insight into its extraordinary capacity for protein secretion. Our analysis, coupled with the genome sequence data, provides a roadmap for constructing enhanced T. reesei strains for industrial applications such as biofuel production.
1,085 citations
TL;DR: Through analysis of the current advances in production of citric, lactic and succinic acid production, guidelines for future developments in this fast-moving field are presented.
750 citations
TL;DR: This review summarizes the current strategies that have been successfully applied during the last years to activate silent gene clusters in filamentous fungi, especially in the genus Aspergillus, and attempts to simulate the natural habitat by co-cultivation of microorganisms from the same ecosystem.
622 citations
TL;DR: W Whole-genome analyses indicate that the genome structures of these two species are highly syntenic and suggest that the genus Metarhizium evolved from plant endophytes or pathogens, andTranscriptional analysis of both fungi during early infection processes provided further insights into the genes and pathways involved in infectivity and specificity.
Abstract: Metarhizium spp. are being used as environmentally friendly alternatives to chemical insecticides, as model systems for studying insect-fungus interactions, and as a resource of genes for biotechnology. We present a comparative analysis of the genome sequences of the broad-spectrum insect pathogen Metarhizium anisopliae and the acridid-specific M. acridum. Whole-genome analyses indicate that the genome structures of these two species are highly syntenic and suggest that the genus Metarhizium evolved from plant endophytes or pathogens. Both M. anisopliae and M. acridum have a strikingly larger proportion of genes encoding secreted proteins than other fungi, while ∼30% of these have no functionally characterized homologs, suggesting hitherto unsuspected interactions between fungal pathogens and insects. The analysis of transposase genes provided evidence of repeat-induced point mutations occurring in M. acridum but not in M. anisopliae. With the help of pathogen-host interaction gene database, ∼16% of Metarhizium genes were identified that are similar to experimentally verified genes involved in pathogenicity in other fungi, particularly plant pathogens. However, relative to M. acridum, M. anisopliae has evolved with many expanded gene families of proteases, chitinases, cytochrome P450s, polyketide synthases, and nonribosomal peptide synthetases for cuticle-degradation, detoxification, and toxin biosynthesis that may facilitate its ability to adapt to heterogenous environments. Transcriptional analysis of both fungi during early infection processes provided further insights into the genes and pathways involved in infectivity and specificity. Of particular note, M. acridum transcribed distinct G-protein coupled receptors on cuticles from locusts (the natural hosts) and cockroaches, whereas M. anisopliae transcribed the same receptor on both hosts. This study will facilitate the identification of virulence genes and the development of improved biocontrol strains with customized properties.
575 citations
Cites background from "Genome sequencing and analysis of t..."
...These families are also expanded in some Aspergilli, where the characterized examples are involved in regulating diverse aspects of primary and secondary metabolism, including protein and polysaccharide degradation [70]....
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TL;DR: This mini-review will discuss the enzymes needed for complete degradation of plant polysaccharides and will give an overview of the latest developments concerning fungal carbohydrate-active enzymes and their corresponding families.
Abstract: Enzymatic degradation of plant polysaccharides has many industrial applications, such as within the paper, food, and feed industry and for sustainable production of fuels and chemicals. Cellulose, hemicelluloses, and pectins are the main components of plant cell wall polysaccharides. These polysaccharides are often tightly packed, contain many different sugar residues, and are branched with a diversity of structures. To enable efficient degradation of these polysaccharides, fungi produce an extensive set of carbohydrate-active enzymes. The variety of the enzyme set differs between fungi and often corresponds to the requirements of its habitat. Carbohydrate-active enzymes can be organized in different families based on the amino acid sequence of the structurally related catalytic modules. Fungal enzymes involved in plant polysaccharide degradation are assigned to at least 35 glycoside hydrolase families, three carbohydrate esterase families and six polysaccharide lyase families. This mini-review will discuss the enzymes needed for complete degradation of plant polysaccharides and will give an overview of the latest developments concerning fungal carbohydrate-active enzymes and their corresponding families.
515 citations
References
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TL;DR: A new approach to rapid sequence comparison, basic local alignment search tool (BLAST), directly approximates alignments that optimize a measure of local similarity, the maximal segment pair (MSP) score.
88,255 citations
"Genome sequencing and analysis of t..." refers methods in this paper
...Sequences of the proteins in CAZy were cut into their constitutive modules (catalytic modules, carbohydrate-binding module (CBMs) and other noncatalytic modules) and the resulting fragments were assembled in a sequence library for Blast searche...
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TL;DR: An overview of the statistical methods, computational tools, and visual exploration modules for data input and the results obtainable in MEGA is provided.
Abstract: With its theoretical basis firmly established in molecular evolutionary and population genetics, the comparative DNA and protein sequence analysis plays a central role in reconstructing the evolutionary histories of species and multigene families, estimating rates of molecular evolution, and inferring the nature and extent of selective forces shaping the evolution of genes and genomes. The scope of these investigations has now expanded greatly owing to the development of high-throughput sequencing techniques and novel statistical and computational methods. These methods require easy-to-use computer programs. One such effort has been to produce Molecular Evolutionary Genetics Analysis (MEGA) software, with its focus on facilitating the exploration and analysis of the DNA and protein sequence variation from an evolutionary perspective. Currently in its third major release, MEGA3 contains facilities for automatic and manual sequence alignment, web-based mining of databases, inference of the phylogenetic trees, estimation of evolutionary distances and testing evolutionary hypotheses. This paper provides an overview of the statistical methods, computational tools, and visual exploration modules for data input and the results obtainable in MEGA.
12,124 citations
TL;DR: TREE-PUZZLE is a program package for quartet-based maximum-likelihood phylogenetic analysis that provides methods for reconstruction, comparison, and testing of trees and models on DNA as well as protein sequences to reduce waiting time for larger datasets.
Abstract: SUMMARY TREE-PUZZLE is a program package for quartet-based maximum-likelihood phylogenetic analysis (formerly PUZZLE, Strimmer and von Haeseler, Mol. Biol. Evol., 13, 964-969, 1996) that provides methods for reconstruction, comparison, and testing of trees and models on DNA as well as protein sequences. To reduce waiting time for larger datasets the tree reconstruction part of the software has been parallelized using message passing that runs on clusters of workstations as well as parallel computers. AVAILABILITY http://www.tree-puzzle.de. The program is written in ANSI C. TREE-PUZZLE can be run on UNIX, Windows and Mac systems, including Mac OS X. To run the parallel version of PUZZLE, a Message Passing Interface (MPI) library has to be installed on the system. Free MPI implementations are available on the Web (cf. http://www.lam-mpi.org/mpi/implementations/).
2,581 citations
"Genome sequencing and analysis of t..." refers methods in this paper
...Maximum likelihood phylogenetic analysis was performed with Tree Puzzl...
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TL;DR: The unfolded protein response and ERAD are dynamic responses required for the coordinated disposal of misfolded proteins even in the absence of acute stress.
1,941 citations
"Genome sequencing and analysis of t..." refers background in this paper
...niger unfolded protein response (UPR) signaling pathway is strikingly different from that in yeas...
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TL;DR: A model in which the activity of UPR signaling pathways reflects the biosynthetic activity of the ER is proposed, which shows that this information is integrated into control of cellular events, which were previously not considered to be under control of ER signaling pathways.
Abstract: Conformational diseases are caused by mutations altering the folding pathway or final conformation of a protein. Many conformational diseases are caused by mutations in secretory proteins and reach from metabolic diseases, e.g. diabetes, to developmental and neurological diseases, e.g. Alzheimer's disease. Expression of mutant proteins disrupts protein folding in the endoplasmic reticulum (ER), causes ER stress, and activates a signaling network called the unfolded protein response (UPR). The UPR increases the biosynthetic capacity of the secretory pathway through upregulation of ER chaperone and foldase expression. In addition, the UPR decreases the biosynthetic burden of the secretory pathway by downregulating expression of genes encoding secreted proteins. Here we review our current understanding of how an unfolded protein signal is generated, sensed, transmitted across the ER membrane, and how downstream events in this stress response are regulated. We propose a model in which the activity of UPR signaling pathways reflects the biosynthetic activity of the ER. We summarize data that shows that this information is integrated into control of cellular events, which were previously not considered to be under control of ER signaling pathways, e.g. execution of differentiation and starvation programs.
1,697 citations