scholarly journals A systematic assessment of current genome-scale metabolic reconstruction tools

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Sebastián N. Mendoza ◽  
Brett G. Olivier ◽  
Douwe Molenaar ◽  
Bas Teusink
2019 ◽  
Author(s):  
S. N. Mendoza ◽  
B. G Olivier ◽  
D Molenaar ◽  
B Teusink

AbstractSeveral genome-scale metabolic reconstruction software platforms have been developed and are being continuously updated. These tools have been widely applied to reconstruct metabolic models for hundreds of microorganisms ranging from important human pathogens to species of industrial relevance. However, these platforms, as yet, have not been systematically evaluated with respect to software quality, best potential uses and intrinsic capacity to generate high-quality, genome-scale metabolic models. It is therefore unclear for potential users which tool best fits the purpose of their research. In this work, we performed a systematic assessment of the current genome-scale reconstruction software platforms. To meet our goal, we first defined a list of features for assessing software quality related to genome-scale reconstruction, which we expect to be useful for the potential users of these tools. Subsequently, we used the feature list to evaluate the performance of each tool. In order to assess the similarity of the draft reconstructions to high-quality models, we compared each tool’s output networks with that of the high-quality, manually curated, models of Lactobacillus plantarum and Bordetella pertussis, representatives of gram-positive and gram-negative bacteria, respectively. We showed that none of the tools outperforms the others in all the defined features and that model builders should carefully choose a tool (or combinations of tools) depending on the intended use of the metabolic model.Author SummaryMetabolic networks that comprise biochemical reactions at genome-scale have become very useful to study and predict the phenotype of important microorganisms. Several software platforms exist to build these metabolic networks. Based on different approaches and utilizing a variety of databases it is, unfortunately, unclear what are the best scenarios to use each of these tools. Hence, to understand the potential uses of these tools, we created a list of relevant features for metabolic reconstruction and we evaluated the tools in all these categories. Here, we show that none of the tools is better than the other in all the evaluated categories; instead, each tool is more suitable for particular purposes. Therefore, users should carefully select the tool(s) that best fit the purpose of their research. This is the first time these tools are systematically evaluated and this overview can be used as a guide for selecting the correct tool(s) for each case.


2009 ◽  
Vol 5 (2) ◽  
pp. e1000285 ◽  
Author(s):  
Patrick F. Suthers ◽  
Madhukar S. Dasika ◽  
Vinay Satish Kumar ◽  
Gennady Denisov ◽  
John I. Glass ◽  
...  

2010 ◽  
Vol 192 (20) ◽  
pp. 5534-5548 ◽  
Author(s):  
Matthew A. Oberhardt ◽  
Joanna B. Goldberg ◽  
Michael Hogardt ◽  
Jason A. Papin

ABSTRACT System-level modeling is beginning to be used to decipher high throughput data in the context of disease. In this study, we present an integration of expression microarray data with a genome-scale metabolic reconstruction of P seudomonas aeruginosa in the context of a chronic cystic fibrosis (CF) lung infection. A genome-scale reconstruction of P. aeruginosa metabolism was tailored to represent the metabolic states of two clonally related lineages of P. aeruginosa isolated from the lungs of a CF patient at different points over a 44-month time course, giving a mechanistic glimpse into how the bacterial metabolism adapts over time in the CF lung. Metabolic capacities were analyzed to determine how tradeoffs between growth and other important cellular processes shift during disease progression. Genes whose knockouts were either significantly growth reducing or lethal in silico were also identified for each time point and serve as hypotheses for future drug targeting efforts specific to the stages of disease progression.


2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Thordis Kristjansdottir ◽  
Elleke F. Bosma ◽  
Filipe Branco dos Santos ◽  
Emre Özdemir ◽  
Markus J. Herrgård ◽  
...  

Abstract Background Lactobacillus reuteri is a heterofermentative Lactic Acid Bacterium (LAB) that is commonly used for food fermentations and probiotic purposes. Due to its robust properties, it is also increasingly considered for use as a cell factory. It produces several industrially important compounds such as 1,3-propanediol and reuterin natively, but for cell factory purposes, developing improved strategies for engineering and fermentation optimization is crucial. Genome-scale metabolic models can be highly beneficial in guiding rational metabolic engineering. Reconstructing a reliable and a quantitatively accurate metabolic model requires extensive manual curation and incorporation of experimental data. Results A genome-scale metabolic model of L. reuteri JCM 1112T was reconstructed and the resulting model, Lreuteri_530, was validated and tested with experimental data. Several knowledge gaps in the metabolism were identified and resolved during this process, including presence/absence of glycolytic genes. Flux distribution between the two glycolytic pathways, the phosphoketolase and Embden–Meyerhof–Parnas pathways, varies considerably between LAB species and strains. As these pathways result in different energy yields, it is important to include strain-specific utilization of these pathways in the model. We determined experimentally that the Embden–Meyerhof–Parnas pathway carried at most 7% of the total glycolytic flux. Predicted growth rates from Lreuteri_530 were in good agreement with experimentally determined values. To further validate the prediction accuracy of Lreuteri_530, the predicted effects of glycerol addition and adhE gene knock-out, which results in impaired ethanol production, were compared to in vivo data. Examination of both growth rates and uptake- and secretion rates of the main metabolites in central metabolism demonstrated that the model was able to accurately predict the experimentally observed effects. Lastly, the potential of L. reuteri as a cell factory was investigated, resulting in a number of general metabolic engineering strategies. Conclusion We have constructed a manually curated genome-scale metabolic model of L. reuteri JCM 1112T that has been experimentally parameterized and validated and can accurately predict metabolic behavior of this important platform cell factory.


2020 ◽  
Vol 21 (4) ◽  
pp. 527-540 ◽  
Author(s):  
Lokanand Koduru ◽  
Hyang Yeon Kim ◽  
Meiyappan Lakshmanan ◽  
Bijayalaxmi Mohanty ◽  
Yi Qing Lee ◽  
...  

2011 ◽  
Vol 193 (7) ◽  
pp. 1710-1717 ◽  
Author(s):  
Y.-C. Liao ◽  
T.-W. Huang ◽  
F.-C. Chen ◽  
P. Charusanti ◽  
J. S. J. Hong ◽  
...  

2006 ◽  
Vol 2 (1) ◽  
Author(s):  
Adam M Feist ◽  
Johannes C M Scholten ◽  
Bernhard Ø Palsson ◽  
Fred J Brockman ◽  
Trey Ideker

2021 ◽  
Author(s):  
Mahsa Sadat Razavi Borghei ◽  
Meysam Mobasheri ◽  
Tabassom Sobati

Abstract Propionibacterium is an anaerobic bacterium with a history of use in the production of Swiss cheese and, more recently, several industrial bioproducts. While the use of this strain for the production of organic acids and secondary metabolites has gained growing interest, the industrial application of the strain requires further improvement in the yield and productivity of the target products. Systems modeling and analysis of metabolic networks are widely leveraged to gain holistic insights into the metabolic features of biotechnologically important strains and to devise metabolic engineering and culture optimization strategies for economically viable bioprocess development. In the present study, a high-quality genome-scale metabolic model of P. freudenreichii ssp. freudenreichii strain DSM 20271 was developed based on the strain’s genome annotation and biochemical and physiological data. The model covers the functions of 23% of the strain’s ORFs and accounts for 711 metabolic reactions and 647 unique metabolites. Literature-based reconstruction of the central metabolism and rigorous refinement of annotation data for establishing gene-protein-reaction associations renders the model a curated omic-scale knowledge base of the organism. Validation of the model against experimental data indicates that the reconstruction can capture the key structural and functional features of P. freudenreichii metabolism, including the growth rate, the pattern of flux distribution, the strain’s aerotolerance behavior, and the change in the mode of metabolic activity during the transition from an anaerobic to an aerobic growth regime. The model also includes an accurately curated pathway of cobalamin biosynthesis, which was used to examine the capacity of the strain to produce vitamin B12 precursors. Constraint-based reconstruction and analysis of the P. freudenreichii metabolic network also provided novel insights into the complexity and robustness of P. freudenreichii energy metabolism. The developed reconstruction, hence, may be used as a platform for the development of P. freudenreichii-based microbial cell factories and bioprocesses.


2019 ◽  
Author(s):  
Thordis Kristjansdottir ◽  
Elleke F. Bosma ◽  
Filipe Branco dos Santos ◽  
Emre Özdemir ◽  
Markus J. Herrgård ◽  
...  

AbstractBackgroundLactobacillus reuteri is a heterofermentative Lactic Acid Bacterium (LAB) that is commonly used for food fermentations and probiotic purposes. Due to its robust properties, it is also increasingly considered for use as a cell factory. It produces several industrially important compounds such as 1,3-propanediol and reuterin natively, but for cell factory purposes, developing improved strategies for engineering and fermentation optimization is crucial. Genome-scale metabolic models can be highly beneficial in guiding rational metabolic engineering. Reconstructing a reliable and a quantitatively accurate metabolic model requires extensive manual curation and incorporation of experimental data.ResultsA genome-scale metabolic model of L. reuteri JCM 1112T was reconstructed and the resulting model, Lreuteri_530, was validated and tested with experimental data. Several knowledge gaps in the metabolism were identified and resolved during this process, including presence/absence of glycolytic genes. Flux distribution between the two glycolytic pathways, the phosphoketolase and Embden-Meyerhof-Parnas pathways, varies considerably between LAB species and strains. As these pathways result in different energy yields, it is important to include strain-specific utilization of these pathways in the model. We determined experimentally that the Embden-Meyerhof-Parnas pathway carried at most 7% of the total glycolytic flux. Predicted growth rates from Lreuteri_530 were in good agreement with experimentally determined values. To further validate the prediction accuracy of Lreuteri_530, the predicted effects of glycerol addition and adhE gene knock-out, which results in impaired ethanol production, were compared to in vivo data. Examination of both growth rates and uptake- and secretion rates of the main metabolites in central metabolism demonstrated that the model was able to accurately predict the experimentally observed effects. Lastly, the potential of L. reuteri as a cell factory was investigated, resulting in a number of general metabolic engineering strategies.ConclusionWe have constructed a manually curated genome-scale metabolic model of L. reuteri JCM 1112T that has been experimentally parameterized and validated and can accurately predict metabolic behavior of this important platform cell factory.


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