| 1. |
- Wortman, J. R., et al.
(författare)
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The 2008 update of the Aspergillus nidulans genome annotation: A community effort
- 2009
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Ingår i: Fungal Genetics and Biology. - : Elsevier BV. - 1096-0937 .- 1087-1845. ; 46, s. S2-S13
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Tidskriftsartikel (refereegranskat)abstract
- The identification and annotation of protein-coding genes is one of the primary goals of whole-genome sequencing projects, and the accuracy of predicting the primary protein products of gene expression is vital to the interpretation of the available data and the design of downstream functional applications. Nevertheless, the comprehensive annotation of eukaryotic genomes remains a considerable challenge. Many genomes submitted to public databases, including those of major model organisms, contain significant numbers of wrong and incomplete gene predictions. We present a community-based reannotation of the Aspergillus nidulans genome with the primary goal of increasing the number and quality of protein functional assignments through the careful review of experts in the field of fungal biology. (C) 2009 Elsevier Inc. All rights reserved.
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| 2. |
- Coutinho, P. M., et al.
(författare)
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Post-genomic insights into the plant polysaccharide degradation potential of Aspergillus nidulans and comparison to Aspergillus niger and Aspergillus oryzae
- 2009
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Ingår i: Fungal Genetics and Biology. - : Elsevier BV. - 1096-0937 .- 1087-1845. ; 46:Suppl 1, s. S161-S169
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Tidskriftsartikel (refereegranskat)abstract
- The plant polysaccharide degradative potential of Aspergillus nidulans was analysed in detail and compared to that of Aspergillus niger and Aspergillus oryzae using a combination of bioinformatics, physiology and transcriptomics. Manual verification indicated that 28.4% of the A. nidulans ORFs analysed in this study do not contain a secretion signal, of which 40% may be secreted through a non-classical method. While significant differences were found between the species in the numbers of ORFs assigned to the relevant CAZy families, no significant difference was observed in growth on polysaccharides. Growth differences were observed between the Aspergilli and Podospora anserina, which has a more different genomic potential for polysaccharide degradation, suggesting that large genomic differences are required to cause growth differences oil polysaccharides, Differences were also detected between the Aspergilli in the presence Of putative regulatory sequences in the promoters of the ORFs Of this Study and correlation of the presence Of putative XlnR binding sites to induction by xylose was detected for A. niger. These data demonstrate differences at genome content, Substrate specificity of the enzymes and gene regulation in these three Aspergilli, which likely reflect their individual adaptation to their natural biotope. (C) 2008 Elsevier Inc. All rights reserved.
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| 3. |
- Herrgård, Markus J, et al.
(författare)
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A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology
- 2008
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Ingår i: Nature Biotechnology. ; 26:10, s. 1155-1160
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Tidskriftsartikel (refereegranskat)abstract
- Genomic data allow the large-scale manual or semi-automated assembly of metabolic network reconstructions, which provide highly curated organism-specific knowledge bases. Although several genome-scale network reconstructions describe Saccharomyces cerevisiae metabolism, they differ in scope and content, and use different terminologies to describe the same chemical entities. This make comparisons between them difficult and underscores the desirability of a consolidated metabolic network that collects and formalizes the 'community knowledge' of yeast metabolism. We describe how we have produced a consensus metabolic network reconstruction for S. cerevisiae. In drafting it, we placed special emphasis on referencing molecules to persistent databases or using database-independent forms, such as SMILES or InChl strings, as this permits their chemical structure to be represented unambiguously and in a manner that permits automated reasoning. The reconstruction is readily available via a publicly accessible database and in the Systems Biology Markup Language (http://www.comp-sys-bio.org/yeastnet). It can be maintained as a resource that serves as a common denominator for studying the systems biology of yeast. Similar strategies should benefit communities studying genome-scale metabolic networks of other organisms.
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| 4. |
- Flagfeldt, D. B., et al.
(författare)
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Characterization of chromosomal integration sites for heterologous gene expression in Saccharomyces cerevisiae
- 2009
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Ingår i: Yeast. - : Wiley. - 1097-0061 .- 0749-503X. ; 26:10, s. 545-551
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Tidskriftsartikel (refereegranskat)abstract
- The construction of mitotically stable yeast strains for heterologous gene or pathway expression often requires chromosomal integration. However, transcription levels vary between different chromosome regions. We therefore characterized 20 different integration sites of the Sacchromyces cerevisiae genome by inserting lacZ as a reporter gene under the control of two different promoters and determining expression levels through enzyme activity measurement. An up to 8.7-fold difference was detected between the sites conferring lowest and highest expression, respectively. This opens the opportunity for modulating gene expression levels while retaining promoter and culture conditions. Copyright (C) 2009 John Wiley & Sons, Ltd.
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| 5. |
- Meijer, S. L., et al.
(författare)
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Gene deletion of cytosolic ATP: citrate lyase leads to altered organic acid production in Aspergillus niger
- 2009
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Ingår i: Journal of Industrial Microbiology and Biotechnology. - : Oxford University Press (OUP). - 1367-5435 .- 1476-5535. ; 36:10, s. 1275-1280
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Tidskriftsartikel (refereegranskat)abstract
- With the availability of the genome sequence of the filamentous fungus Aspergillus niger, the use of targeted genetic modifications has become feasible. This, together with the fact that A. niger is well established industrially, makes this fungus an attractive micro-organism for creating a cell factory platform for production of chemicals. Using molecular biology techniques, this study focused on metabolic engineering of A. niger to manipulate its organic acid production in the direction of succinic acid. The gene target for complete gene deletion was cytosolic ATP: citrate lyase (acl), which had previously been identified by using genome-scale stoichiometric metabolic model simulations. The acl gene was deleted using the bipartite gene-targeting method, and the mutant was characterized in batch cultivation. It was found that the succinic acid yield was increased threefold by deleting the acl gene. Additionally, the total amount of organic acids produced in the deletion strain was significantly increased. Genome-scale stoichiometric metabolic predictions can be used for identifying gene targets. Deletion of the acl led to increased succinic acid production by A. niger.
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| 6. |
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| 7. |
- Panagiotou, Gianni, 1974, et al.
(författare)
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Studies of the Production of Fungal Polyketides in Aspergillus nidulans by Using Systems Biology Tools
- 2009
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Ingår i: Applied and Environmental Microbiology. - 1098-5336 .- 0099-2240. ; 75:7, s. 2212-2220
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Tidskriftsartikel (refereegranskat)abstract
- Many filamentous fungi produce polyketide molecules with great significance as human pharmaceuticals; these molecules include the cholesterol-lowering compound lovastatin, which was originally isolated from Aspergillus terreus. The chemical diversity and potential uses of these compounds are virtually unlimited, and it is thus of great interest to develop a well-described microbial production platform for polyketides. Using genetic engineering tools available for the model organism Aspergillus nidulans, we constructed two recombinant strains, one expressing the Penicillium grisefulvum 6-methylsalicylic acid (6-MSA) synthase gene and one expressing the 6-MSA syntase gene and overexpressing the native xylulose-5-phosphate phosphoketolase gene (xpkA) for increasing the pool of polyketide precursor levels. The physiology of the recombinant strains and that of a reference wild-type strain were characterized on glucose, xylose, glycerol, and ethanol media in controlled bioreactors. Glucose was found to be the preferred carbon source for 6-MSA production, and 6-MSA concentrations up to 455 mg/liter were obtained for the recombinant strain harboring the 6-MSA gene. Our findings indicate that overexpression of xpkA does not directly improve 6-MSA production on glucose, but it is possible, if the metabolic flux through the lower part of glycolysis is reduced, to obtain quite high yields for conversion of sugar to 6-MSA. Systems biology tools were employed for in-depth analysis of the metabolic processes. Transcriptome analysis of 6-MSA-producing strains grown on glucose and xylose in the presence and absence of xpkA overexpression, combined with flux and phsyiology data, enabled us to propose an xpkA-msaS interaction model describing the competition between biomass formation and 6-MSA production for the available acetyl coenzyme A.
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| 8. |
- Panagiotou, Gianni, 1974, et al.
(författare)
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Systems Analysis Unfolds the Relationship between the Phosphoketolase Pathway and Growth in Aspergillus nidulans
- 2008
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 3:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Aspergillus nidulans is an important model organism for studies on fundamental eukaryotic cell biology and on industrial processes due to its close relation to A. niger and A. oryzae. Here we identified the gene coding for a novel metabolic pathway in A. nidulans, namely the phosphoketolase pathway, and investigated the role of an increased phosphoketolase activity. Methodology/Principal findings: Over-expression of the phosphoketolase gene (phk) improved the specific growth rate on xylose, glycerol and ethanol. Transcriptome analysis showed that a total of 1,222 genes were significantly affected by over-expression of the phk, while more than half of the affected genes were carbon source specific. During growth on glucose medium, the transcriptome analysis showed that the response to phk over-expression is targeted to neutralize the effect of the over-expression by regulating the acetate metabolism and initiate a growth dampening response. Conclusions/Significance: Metabolic flux analysis using 13C-labelled glucose, showed that over-expression of phosphoketolase added flexibility to the central metabolism. Our findings further suggests that A. nidulans is not optimized for growth on xylose, glycerol or ethanol as the sole carbon sources.
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| 9. |
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| 10. |
- Petranovic Nielsen, Dina, 1975, et al.
(författare)
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Can yeast systems biology contribute to the understanding of human disease?
- 2008
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Ingår i: Trends in Biotechnology. ; 26:11, s. 584-590
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Tidskriftsartikel (refereegranskat)abstract
- Saccharomyces cerevisiae is a unicellular eukaryal microorganism that has traditionally been regarded either as a model system for investigating cellular physiology or as a cell factory for biotechnological use, for example for the production of fuels and commodity chemicals such as lactate or pharmaceuticals, including human insulin and HPV vaccines. Systems biology has recently gained momentum and has successfully been used for mapping complex regulatory networks and resolving the dynamics of signal transduction pathways. So far, yeast systems biology has mainly focused on the development of new methods and concepts. There are also some examples of the application of yeast systems biology for improving biotechnological processes. We discuss here how yeast systems biology could be used in elucidating fundamental cellular principles such as those relevant for the study of molecular mechanisms underlying complex human diseases, including the metabolic syndrome and ageing.
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