| 1. |
- Cvijovic, Marija, 1977, et al.
(författare)
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BioMet Toolbox: genome-wide analysis of metabolism
- 2010
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 38:SUPPL. 2, s. W144-W149
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Tidskriftsartikel (refereegranskat)abstract
- The rapid progress of molecular biology tools for directed genetic modifications, accurate quantitative experimental approaches, high-throughput measurements, together with development of genome sequencing has made the foundation for a new area of metabolic engineering that is driven by metabolic models. Systematic analysis of biological processes by means of modelling and simulations has made the identification of metabolic networks and prediction of metabolic capabilities under different conditions possible. For facilitating such systemic analysis, we have developed the BioMet Toolbox, a web-based resource for stoichiometric analysis and for integration of transcriptome and interactome data, thereby exploiting the capabilities of genome-scale metabolic models. The BioMet Toolbox provides an effective user-friendly way to perform linear programming simulations towards maximized or minimized growth rates, substrate uptake rates and metabolic production rates by detecting relevant fluxes, simulate single and double gene deletions or detect metabolites around which major transcriptional changes are concentrated. These tools can be used for high-throughput in silico screening and allows fully standardized simulations. Model files for various model organisms (fungi and bacteria) are included. Overall, the BioMet Toolbox serves as a valuable resource for exploring the capabilities of these metabolic networks. BioMet Toolbox is freely available at www.sysbio.se/BioMet/.
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| 2. |
- Ågren, Rasmus, 1982, et al.
(författare)
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The RAVEN Toolbox and Its Use for Generating a Genome-scale Metabolic Model for Penicillium chrysogenum
- 2013
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Ingår i: PLoS Computational Biology. - : Public Library of Science (PLoS). - 1553-734X .- 1553-7358. ; 9:3, s. e1002980-
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Tidskriftsartikel (refereegranskat)abstract
- We present the RAVEN (Reconstruction, Analysis and Visualization of Metabolic Networks) Toolbox: a software suite that allows for semi-automated reconstruction of genome-scale models. It makes use of published models and/or the KEGG database, coupled with extensive gap-filling and quality control features. The software suite also contains methods for visualizing simulation results and omics data, as well as a range of methods for performing simulations and analyzing the results. The software is a useful tool for system-wide data analysis in a metabolic context and for streamlined reconstruction of metabolic networks based on protein homology. The RAVEN Toolbox workflow was applied in order to reconstruct a genome-scale metabolic model for the important microbial cell factory Penicillium chrysogenum Wisconsin54-1255. The model was validated in a bibliomic study of in total 440 references, and it comprises 1471 unique biochemical reactions and 1006 ORFs. It was then used to study the roles of ATP and NADPH in the biosynthesis of penicillin, and to identify potential metabolic engineering targets for maximization of penicillin production.
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| 3. |
- Geijer, Cecilia, 1980, et al.
(författare)
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Time course gene expression profiling of yeast spore germination reveals a network of transcription factors orchestrating the global response
- 2012
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background Spore germination of the yeast Saccharomyces cerevisiae is a multi-step developmental path on which dormant spores re-enter the mitotic cell cycle and resume vegetative growth. Upon addition of a fermentable carbon source and nutrients, the outer layers of the protective spore wall are locally degraded, the tightly packed spore gains volume and an elongated shape, and eventually the germinating spore re-enters the cell cycle. The regulatory pathways driving this process are still largely unknown. Here we characterize the global gene expression profiles of germinating spores and identify potential transcriptional regulators of this process with the aim to increase our understanding of the mechanisms that control the transition from cellular dormancy to proliferation. Results Employing detailed gene expression time course data we have analysed the reprogramming of dormant spores during the transition to proliferation stimulated by a rich growth medium or pure glucose. Exit from dormancy results in rapid and global changes consisting of different sequential gene expression subprograms. The regulated genes reflect the transition towards glucose metabolism, the resumption of growth and the release of stress, similar to cells exiting a stationary growth phase. High resolution time course analysis during the onset of germination allowed us to identify a transient up-regulation of genes involved in protein folding and transport. We also identified a network of transcription factors that may be regulating the global response. While the expression outputs following stimulation by rich glucose medium or by glucose alone are qualitatively similar, the response to rich medium is stronger. Moreover, spores sense and react to amino acid starvation within the first 30 min after germination initiation, and this response can be linked to specific transcription factors. Conclusions Resumption of growth in germinating spores is characterized by a highly synchronized temporal organisation of up- and down-regulated genes which reflects the metabolic reshaping of the quickening spores.
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| 4. |
- Hong, Kuk-ki, 1976, et al.
(författare)
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Unravelling evolutionary strategies of yeast for improving galactose utilization through integrated systems level analysis
- 2011
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 108:29, s. 12179-12184
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Tidskriftsartikel (refereegranskat)abstract
- Identification of the underlying molecular mechanisms for a derived phenotype by adaptive evolution is difficult. Here, we performed a systems-level inquiry into the metabolic changes occurring in the yeast Saccharomyces cerevisiae as a result of its adaptive evolution to increase its specific growth rate on galactose and related these changes to the acquired phenotypic properties. Three evolved mutants (62A, 62B, and 62C) with higher specific growth rates and faster specific galactose uptake were isolated. The evolved mutants were compared with a reference strain and two engineered strains, SO16 and PGM2, which also showed higher galactose uptake rate in previous studies. The profile of intermediates in galactose metabolism was similar in evolved and engineered mutants, whereas reserve carbohydrates metabolism was specifically elevated in the evolved mutants and one evolved strain showed changes in ergosterol biosynthesis. Mutations were identified in proteins involved in the global carbon sensing Ras/PKA pathway, which is known to regulate the reserve carbohydrates metabolism. We evaluated one of the identified mutations, RAS2(Tyr112), and this mutation resulted in an increased specific growth rate on galactose. These results show that adaptive evolution results in the utilization of unpredicted routes to accommodate increased galactose flux in contrast to rationally engineered strains. Our study demonstrates that adaptive evolution represents a valuable alternative to rational design in bioengineering of improved strains and, that through systems biology, it is possible to identify mutations in evolved strain that can serve as unforeseen metabolic engineering targets for improving microbial strains for production of biofuels and chemicals.
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| 5. |
- Nijkamp, J. F., et al.
(författare)
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De novo sequencing, assembly and analysis of the genome of the laboratory strain Saccharomyces cerevisiae CEN.PK113-7D, a model for modern industrial biotechnology
- 2012
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Ingår i: Microbial Cell Factories. - : Springer Science and Business Media LLC. - 1475-2859. ; 11, s. Article Number: 36-
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Tidskriftsartikel (refereegranskat)abstract
- Saccharomyces cerevisiae CEN.PK 113-7D is widely used for metabolic engineering and systems biology research in industry and academia. We sequenced, assembled, annotated and analyzed its genome. Single-nucleotide variations (SNV), insertions/deletions (indels) and differences in genome organization compared to the reference strain S. cerevisiae S288C were analyzed. In addition to a few large deletions and duplications, nearly 3000 indels were identified in the CEN.PK113-7D genome relative to S288C. These differences were overrepresented in genes whose functions are related to transcriptional regulation and chromatin remodelling. Some of these variations were caused by unstable tandem repeats, suggesting an innate evolvability of the corresponding genes. Besides a previously characterized mutation in adenylate cyclase, the CEN. PK113-7D genome sequence revealed a significant enrichment of non-synonymous mutations in genes encoding for components of the cAMP signalling pathway. Some phenotypic characteristics of the CEN. PK113-7D strains were explained by the presence of additional specific metabolic genes relative to S288C. In particular, the presence of the BIO1 and BIO6 genes correlated with a biotin prototrophy of CEN. PK113-7D. Furthermore, the copy number, chromosomal location and sequences of the MAL loci were resolved. The assembled sequence reveals that CEN. PK113-7D has a mosaic genome that combines characteristics of laboratory strains and wild-industrial strains.
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| 6. |
- Otero, José Manuel, 1979, et al.
(författare)
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Whole genome sequencing of Saccharomyces cerevisiae: from genotype to phenotype for improved metabolic engineering applications
- 2010
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 11:1, s. 723-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The need for rapid and efficient microbial cell factory design and construction are possible through the enabling technology, metabolic engineering, which is now being facilitated by systems biology approaches. Metabolic engineering is often complimented by directed evolution, where selective pressure is applied to a partially genetically engineered strain to confer a desirable phenotype. The exact genetic modification or resulting genotype that leads to the improved phenotype is often not identified or understood to enable further metabolic engineering.Results: In this work we performed whole genome high-throughput sequencing and annotation can be used to identify single nucleotide polymorphisms (SNPs) between Saccharomyces cerevisiae strains S288c and CEN.PK113-7D. The yeast strain S288c was the first eukaryote sequenced, serving as the reference genome for the Saccharomyces Genome Database, while CEN.PK113-7D is a preferred laboratory strain for industrial biotechnology research. A total of 13,787 high-quality SNPs were detected between both strains (reference strain: S288c). Considering only metabolic genes (782 of 5,596 annotated genes), a total of 219 metabolism specific SNPs are distributed across 158 metabolic genes, with 85 of the SNPs being nonsynonymous (e. g., encoding amino acid modifications). Amongst metabolic SNPs detected, there was pathway enrichment in the galactose uptake pathway (GAL1, GAL10) and ergosterol biosynthetic pathway (ERG8, ERG9). Physiological characterization confirmed a strong deficiency in galactose uptake and metabolism in S288c compared to CEN.PK113-7D, and similarly, ergosterol content in CEN.PK113-7D was significantly higher in both glucose and galactose supplemented cultivations compared to S288c. Furthermore, DNA microarray profiling of S288c and CEN.PK113-7D in both glucose and galactose batch cultures did not provide a clear hypothesis for major phenotypes observed, suggesting that genotype to phenotype correlations are manifested post-transcriptionally or post-translationally either through protein concentration and/or function.Conclusions: With an intensifying need for microbial cell factories that produce a wide array of target compounds, whole genome high-throughput sequencing and annotation for SNP detection can aid in better reducing and defining the metabolic landscape. This work demonstrates direct correlations between genotype and phenotype that provides clear and high-probability of success metabolic engineering targets. The genome sequence, annotation, and a SNP viewer of CEN.PK113-7D are deposited at http://www.sysbio.se/cenpk.
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| 7. |
- Piddocke, M. P., et al.
(författare)
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Revealing the beneficial effect of protease supplementation to high gravity beer fermentations using "-omics" techniques
- 2011
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Ingår i: Microbial Cell Factories. - : Springer Science and Business Media LLC. - 1475-2859. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Addition of sugar syrups to the basic wort is a popular technique to achieve higher gravity in beer fermentations, but it results in dilution of the free amino nitrogen (FAN) content in the medium. The multicomponent protease enzyme Flavourzyme has beneficial effect on the brewer's yeast fermentation performance during high gravity fermentations as it increases the initial FAN value and results in higher FAN uptake, higher specific growth rate, higher ethanol yield and improved flavour profile. Results: In the present study, transcriptome and metabolome analysis were used to elucidate the effect on the addition of the multicomponent protease enzyme Flavourzyme and its influence on the metabolism of the brewer's yeast strain Weihenstephan 34/70. The study underlines the importance of sufficient nitrogen availability during the course of beer fermentation. The applied metabolome and transcriptome analysis allowed mapping the effect of the wort sugar composition on the nitrogen uptake. Conclusion: Both the transcriptome and the metabolome analysis revealed that there is a significantly higher impact of protease addition for maltose syrup supplemented fermentations, while addition of glucose syrup to increase the gravity in the wort resulted in increased glucose repression that lead to inhibition of amino acid uptake and hereby inhibited the effect of the protease addition.
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| 8. |
- Raethong, Nachon, et al.
(författare)
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Optimizing cultivation of Cordyceps militaris for fast growth and cordycepin overproduction using rational design of synthetic media
- 2020
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Ingår i: Computational and Structural Biotechnology Journal. - : Elsevier BV. - 2001-0370. ; 18, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Cordyceps militaris is an entomopathogenic fungus which is often used in Asia as a traditional medicine developed from age-old wisdom. Presently, cordycepin from C. militaris is a great interest in medicinal applications. However, cellular growth of C. militaris and the association with cordycepin production remain poorly understood. To explore the metabolism of C. militaris as potential cell factories in medical and biotechnology applications, this study developed a high-quality genome-scale metabolic model of C. militaris, iNR1329, based on its genomic content and physiological data. The model included a total of 1329 genes, 1821 biochemical reactions, and 1171 metabolites among 4 different cellular compartments. Its in silico growth simulation results agreed well with experimental data on different carbon sources. iNR1329 was further used for optimizing the growth and cordycepin overproduction using a novel approach, POPCORN, for rational design of synthetic media. In addition to the high-quality GEM iNR1329, the presented POPCORN approach was successfully used to rationally design an optimal synthetic medium with C:N ratio of 8:1 for enhancing 3.5-fold increase in cordycepin production. This study thus provides a novel insight into C. militaris physiology and highlights a potential GEM-driven method for synthetic media design and metabolic engineering application. The iNR1329 and the POPCORN approach are available at the GitHub repository: https://github.com/sysbiomics/Cordyceps_militaris-GEM.
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| 9. |
- Rokem, J. S., et al.
(författare)
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Comparative Metabolic Capabilities for Micrococcus luteus NCTC 2665, the "Fleming" Strain, and Actinobacteria
- 2011
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Ingår i: Biotechnology and Bioengineering. - : Wiley. - 0006-3592 .- 1097-0290. ; 108:11, s. 2770-2775
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Tidskriftsartikel (refereegranskat)abstract
- Putative gene predictions of the Gram positive actinobacteria Micrococcus luteus (NCTC 2665, "Fleming strain") was used to construct a genome scale reconstruction of the metabolic network for this organism. The metabolic network comprises 586 reactions and 551 metabolites, and accounts for 21% of the genes in the genome. The reconstruction was based on the annotated genome and available biochemical information. M. luteus has one of the smallest genomes of actinobacteria with a circular chromosome of 2,501,097 base pairs and a GC content of 73%. The metabolic pathways required for biomass production in silico were determined based on earlier models of actinobacteria. The in silico network is used for metabolic comparison of M. luteus with other actinomycetes, and hence provides useful information for possible future biotechnological exploitation of this organism, e. g., for production of biofuels.
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| 10. |
- Ruenwai, R., et al.
(författare)
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Heterologous production of polyunsaturated fatty acids in Saccharomyces cerevisiae causes a global transcriptional response resulting in reduced proteasomal activity and increased oxidative stress
- 2011
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Ingår i: Biotechnology journal. - : Wiley. - 1860-6768 .- 1860-7314. ; 6:3, s. 343-356
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Tidskriftsartikel (refereegranskat)abstract
- Due to their health benefits there is much interest in developing microbial processes for efficient production of polyunsaturated fatty acids (PUFAs). In this study we co-expressed Mucor rouxii Delta(12)- and Delta(6)-desaturase genes in Saccharomyces cerevisiae, which resulted in a yeast strain that accumulated linoleic acid and gamma-linolenic acid in the different lipid species. Additionally, the strain contained higher levels of phospholipids and lower levels of ergosterol than the reference strain. Integrated analysis of the transcriptome revealed decreased expression of genes involved in ergosterol biosynthesis, but more unexpectedly it also pointed towards attenuated activity of the ubiquitin-proteasome system and a reduced oxidative stress response. In vitro and in vivo measurements showed reduced levels of all three proteasomal activities and also increased levels of reactive oxidative species in the PUFA-producing strain. Overall our results clearly show that PUFAs in yeast can be detrimental for several key cellular pathways, such as the oxidative stress response and proteasomal activity, suggesting that the membrane composition is of vital importance for these processes.
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| 11. |
- Salazar Pena, Margarita, 1979, et al.
(författare)
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Uncovering transcriptional regulation of glycerol metabolism in Aspergilli through genome-wide gene expression data analysis
- 2009
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Ingår i: Molecular Genetics and Genomics. - : Springer Science and Business Media LLC. - 1617-4615 .- 1617-4623. ; 282:6, s. 571-586
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Tidskriftsartikel (refereegranskat)abstract
- Glycerol is catabolized by a wide range of microorganisms including Aspergillus species. To identify the transcriptional regulation of glycerol metabolism in Aspergillus, we analyzed data from triplicate batch fermentations of three different Aspergilli (Aspergillus nidulans, Aspergillus oryzae and Aspergillus niger) with glucose and glycerol as carbon sources. Protein comparisons and cross-analysis with gene expression data of all three species resulted in the identification of 88 genes having a conserved response across the three Aspergilli. A promoter analysis of the up-regulated genes led to the identification of a conserved binding site for a putative regulator to be 5'-TGCGGGGA-3', a binding site that is similar to the binding site for Adr1 in yeast and humans. We show that this Adr1 consensus binding sequence was over-represented on promoter regions of several genes in A. nidulans, A. oryzae and A. niger. Our transcriptome analysis indicated that genes involved in ethanol, glycerol, fatty acid, amino acids and formate utilization are putatively regulated by Adr1 in Aspergilli as in Saccharomyces cerevisiae and this transcription factor therefore is likely to be cross-species conserved among Saccharomyces and distant Ascomycetes. Transcriptome data were further used to evaluate the high osmolarity glycerol pathway. All the components of this pathway present in yeast have orthologues in the three Aspergilli studied and its gene expression response suggested that this pathway functions as in S. cerevisiae. Our study clearly demonstrates that cross-species evolutionary comparisons among filamentous fungi, using comparative genomics and transcriptomics, are a powerful tool for uncovering regulatory systems.
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| 12. |
- Vongsangnak, Wanwipa, 1982, et al.
(författare)
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Analysis of Genome-Wide Coexpression and Coevolution of Aspergillus oryzae and Aspergillus niger
- 2010
-
Ingår i: OMICS A Journal of Integrative Biology. - : Mary Ann Liebert Inc. - 1536-2310 .- 1557-8100. ; 14:2, s. 165-175
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of coexpressed genes in response to different perturbations at the genome-level can provide new insight into global regulatory structures. Here we performed integrated data analysis for a crossspecies comparative investigation by exploring genomes and transcriptional coexpression profiles in Aspergillus oryzae and Aspergillus niger. Based on our analysis of conserved coexpressed genes, fatty acid catabolism via beta-oxidation, fatty acid transport, the glyoxylate bypass, and peroxisomal biogenesis were identified as core coevolved pathways between the two species. The occurrence of coexpression patterns, allowed for identification of DNA regulatory motifs and putative corresponding transcription factors, and we hereby show that comparative transcriptome analysis between two closely related fungi allows for identification of how genes involved in the utilization of fatty acids, peroxisomal biogenesis, and the glyoxylate bypass are regulated. Interestingly, "CCTCGG'' was identified as a core binding site for the putative FarA and FarB transcription factors that govern the underlined biological processes. Phylogeny and domain architecture analysis of amino acid sequences of FarA and FarB in eight species of aspergilli, clearly indicate that these proteins are evolutionarily conserved across Aspergillus species as well as they are conserved in other fungi.
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| 13. |
- Vongsangnak, Wanwipa, 1982, et al.
(författare)
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Genome-scale metabolic representation of Amycolatopsis balhimycina
- 2012
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Ingår i: Biotechnology and Bioengineering. - : Wiley. - 0006-3592 .- 1097-0290. ; 109:7, s. 1798-1807
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Tidskriftsartikel (refereegranskat)abstract
- Infection caused by methicillin-resistant Staphylococcus aureus (MRSA) is an increasing societal problem. Typically, glycopeptide antibiotics are used in the treatment of these infections. The most comprehensively studied glycopeptide antibiotic biosynthetic pathway is that of balhimycin biosynthesis in Amycolatopsis balhimycina. The balhimycin yield obtained by A. balhimycina is, however, low and there is therefore a need to improve balhimycin production. In this study, we performed genome sequencing, assembly and annotation analysis of A. balhimycina and further used these annotated data to reconstruct a genome-scale metabolic model for the organism. Here we generated an almost complete A. balhimycina genome sequence comprising 10,562,587 base pairs assembled into 2,153 contigs. The high GC-genome (similar to 69%) includes 8,585 open reading frames (ORFs). We used our integrative toolbox called SEQTOR for functional annotation and then integrated annotated data with biochemical and physiological information available for this organism to reconstruct a genome-scale metabolic model of A. balhimycina. The resulting metabolic model contains 583 ORFs as protein encoding genes (7% of the predicted 8,585 ORFs), 407 EC numbers, 647 metabolites and 1,363 metabolic reactions. During the analysis of the metabolic model, linear, quadratic and evolutionary programming algorithms using flux balance analysis (FBA), minimization of metabolic adjustment (MOMA), and OptGene, respectively were applied as well as phenotypic behavior and improved balhimycin production were simulated. The A. balhimycina model shows a good agreement between in silico data and experimental data and also identifies key reactions associated with increased balhimycin production. The reconstruction of the genome-scale metabolic model of A. balhimycina serves as a basis for physiological characterization. The model allows a rational design of engineering strategies for increasing balhimycin production in A. balhimycina and glycopeptide production in general.
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| 14. |
- Vongsangnak, Wanwipa, 1982, et al.
(författare)
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Genome-wide analysis of maltose utilization and regulation in aspergilli
- 2009
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Ingår i: Microbiology. - : Microbiology Society. - 1350-0872 .- 1465-2080. ; 155:12, s. 3893-3902
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Tidskriftsartikel (refereegranskat)abstract
- Maltose utilization and regulation in aspergilli is of great importancefor cellular physiology and industrial fermentation processes.In Aspergillus oryzae, maltose utilization requires a functionalMAL locus, each composed of three genes: MALR encoding a regulatoryprotein, MALT encoding maltose permease and MALS encodingmaltase. Through a comparative genome and transcriptomeanalysis we show that the MAL regulon system is active in A.oryzae while it is not present in Aspergillus niger. In order to utilizemaltose, A. niger requires a different regulatory system thatinvolves the AmyR regulator for glucoamylase (glaA) induction.Analysis of reporter metabolites and subnetworks illustrate themajor route of maltose transport and metabolism in A. oryzae. Thisdemonstrates that overall metabolic responses of A. oryzae occur interms of genes, enzymes, and metabolites when altering the carbonsource. Although the amount of knowledge on maltose transportand metabolism is far from being complete in Aspergillus spp., ourstudy not only helps to understand the sugar preference in industrialfermentation processes, but also indicates how maltose affectsgene expression and overall metabolism.
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| 15. |
- Vongsangnak, Wanwipa, 1982, et al.
(författare)
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Improved annotation through genome-scale metabolic modeling of Aspergillus oryzae
- 2008
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Ingår i: BMC Genomics. ; 9:245
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Tidskriftsartikel (refereegranskat)abstract
- Background: Since ancient times the filamentous fungus Aspergillus oryzae has been used in the fermenation industry for the production of fermented sauces and the production of industrial enzymes. Recently, the genome sequence of A. oryzae with 12,074 annotated genes was released but the number of hypothetical proteins accounted for more than 50% of the annotated genes. Considering the industrial importance of this fungus, it is therefore valuable to improve the annotation and further integrate genomic information with biochemical and physiological information available for this microorganism and other related fungi. Here we proposed the gene prediction by construction of an A. oryzae Expressed Sequence Tag (EST) library, sequencing and assembly. We enhanced the function assignment by our developed annotation strategy. The resulting better annotation was used to reconstruct the metabolic network leading to a genome scale metabolic model of A. oryzae.Results: Our assembled EST sequences we identified 1,046 newly predicted genes in the A. oryzae genome. Furthermore, it was possible to assign putative protein functions to 398 of the newly predicted genes. Noteworthy, our annotation strategy resulted in assignment of new putative functions to 1,469 hypothetical proteins already present in the A. oryzae genome database. Using the substantially improved annotated genome we reconstructed the metabolic network of A. oryzae. This network contains 729 enzymes, 1,314 enzyme-encoding genes, 1,073 metabolites and 1,846 (1,053 unique) biochemical reactions. The metabolic reactions are compartmentalized into the cytosol, the mitochondria, the peroxisome and the extracellular space. Transport steps between the compartments and the extracellular space represent 281 reactions, of which 161 are unique. The metabolic model was validated and shown to correctly describe the phenotypic behavior of A. oryzae grown on different carbon sources. Conclusion: A much enhanced annotation of the A. oryzae genome was performed and a genome-scale metabolic model of A. oryzae was reconstructed. The model accurately predicted the growth and biomass yield on different carbon sources. The model serves as an important resource for gaining further insight into understanding of A. oryzae physiology.
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| 16. |
- Vongsangnak, Wanwipa, 1982, et al.
(författare)
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Integrated Analysis of the Global Transcriptional Response to alpha-Amylase Over-Production by Aspergillus oryzae
- 2011
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Ingår i: Biotechnology and Bioengineering. - : Wiley. - 0006-3592 .- 1097-0290. ; 108:5, s. 1130-1139
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Tidskriftsartikel (refereegranskat)abstract
- The filamentous fungus Aspergillus oryzae is an important microbial cell factory for industrial production of many enzymes, such as alpha-amylase. In order to optimize the industrial enzyme production process, there is a need to understand fundamental processes underlying enzyme production, here under how enzyme production links to metabolism through global regulation. Through a genome-scale metabolic network for integrated analysis of transcriptome data and flux calculation, we identified key players (genes, enzymes, proteins, and metabolites) involved in the processes of enzyme synthesis and secretion, nucleotide metabolism, and amino acid metabolism that can be the potential targets for improving industrial enzyme production. Biotechnol. Bioeng. 2011;108: 1130-1139.
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| 17. |
- Vongsangnak, Wanwipa, 1982
(författare)
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SYSBIOMICS of Aspergilli: SYStems Biology, BIoinformatics and OMICS analysis of Aspergilli cell factories
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aspergilli represent a group of filamentous fungi that plays a key role in industrialbiotechnology, and as human, animal and plant pathogens. Here three Aspergillus species,namely Aspergillus oryzae, Aspergillus niger and Aspergillus nidulans are considered. Thesethree species serve as working horses in industrial production of enzymes and chemicals andas key models for basic scientific work. Due to their wide applications, it is valuable to gainunderstanding of their metabolism, regulation and evolution with respect to genotypes andphenotypes, as this may lead to improved industrial fermentation processes for desiredproduct formation (e.g. enzymes). We therefore applied three approaches for thisinvestigation, namely SYStems biology, BIoinformatics and OMICS analysis(SYSBIOMICS). Firstly, we developed BIoinformatics methods to improve the genomeannotation of A. oryzae and this improved annotation was used to reconstruct a high qualitygenome-scale metabolic network that could be used for mathematical modeling of thephysiology and for OMICS data integration, which are the core of SYStems biology.Secondly, we designed a tri-Aspergillus DNA microarray chip to monitor the globalregulation response at the transcriptional level. This DNA chip has been exploited to revealconserved regulatory responses through evolution in the three aspergilli in response to changein carbon source. This resulted in mapping of key regulatory points of metabolism in thesefungi, and it showed that SYSBIOMICS analysis of transcriptional data can lead toreconstruction of how carbon metabolism is regulated. Lastly, we also applied theSYSBIOMICS concept to identify possible key players/targets associated with proteinproduction in a high producing strain of A. oryzae. This analysis may enable diagnosis andimprovement of industrial process of protein production. In conclusion, through a number ofstudies, it has been demonstrated in this thesis that SYSBIOMICS can find wide applicationsin industrial biotechnology and assist in improving industrial process required for sustainableproduction of enzymes and chemicals in the future.
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| 18. |
- Vongsangnak, Wanwipa, 1982, et al.
(författare)
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Systems biology methods and developments of filamentous fungi in relation to the production of food ingredients
- 2013
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Ingår i: Microbial Production of Food Ingredients, Enzymes and Nutraceuticals. - : Elsevier. - 9780857093431 ; , s. 19-41
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Systems biology is rapidly evolving in many areas of biological sciences. In this chapter, we present a review of systems biology of filamentous fungi in relation to the production of enzymes, chemicals and food ingredients. We summarize the current status of systems biology through functional genomics (i.e. genomics, transcriptomics, proteomics, metabolomics) and bioinformatics of different food-related filamentous fungi. In addition, we present a number of case studies dealing with systems biology and functional genomics through the development of a genome-scale metabolic model of filamentous fungi, which serve as important cell factories in food biotechnology. © 2013 Woodhead Publishing Limited. All rights reserved.
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