Genome-scale reconstruction and analysis of the Pseudomonas putida KT2440 metabolic network facilitates applications in biotechnology.
Name:
puchalka et al_final.pdf
Size:
663.5Kb
Format:
PDF
Description:
Open Access publication
Average rating
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Star rating
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Authors
Puchałka, JacekOberhardt, Matthew A
Godinho, Miguel
Bielecka, Agata
Regenhardt, Daniela
Timmis, Kenneth N
Papin, Jason A
Martins dos Santos, Vítor A P
Issue Date
2008-10
Metadata
Show full item recordAbstract
A cornerstone of biotechnology is the use of microorganisms for the efficient production of chemicals and the elimination of harmful waste. Pseudomonas putida is an archetype of such microbes due to its metabolic versatility, stress resistance, amenability to genetic modifications, and vast potential for environmental and industrial applications. To address both the elucidation of the metabolic wiring in P. putida and its uses in biocatalysis, in particular for the production of non-growth-related biochemicals, we developed and present here a genome-scale constraint-based model of the metabolism of P. putida KT2440. Network reconstruction and flux balance analysis (FBA) enabled definition of the structure of the metabolic network, identification of knowledge gaps, and pin-pointing of essential metabolic functions, facilitating thereby the refinement of gene annotations. FBA and flux variability analysis were used to analyze the properties, potential, and limits of the model. These analyses allowed identification, under various conditions, of key features of metabolism such as growth yield, resource distribution, network robustness, and gene essentiality. The model was validated with data from continuous cell cultures, high-throughput phenotyping data, (13)C-measurement of internal flux distributions, and specifically generated knock-out mutants. Auxotrophy was correctly predicted in 75% of the cases. These systematic analyses revealed that the metabolic network structure is the main factor determining the accuracy of predictions, whereas biomass composition has negligible influence. Finally, we drew on the model to devise metabolic engineering strategies to improve production of polyhydroxyalkanoates, a class of biotechnologically useful compounds whose synthesis is not coupled to cell survival. The solidly validated model yields valuable insights into genotype-phenotype relationships and provides a sound framework to explore this versatile bacterium and to capitalize on its vast biotechnological potential.Citation
Genome-scale reconstruction and analysis of the Pseudomonas putida KT2440 metabolic network facilitates applications in biotechnology. 2008, 4 (10):e1000210 PLoS Comput. Biol.Affiliation
Synthetic and Systems Biology Group, Helmholtz Center for Infection Research (HZI), Braunschweig, Germany.Journal
PLoS computational biologyPubMed ID
18974823Type
ArticleLanguage
enISSN
1553-7358ae974a485f413a2113503eed53cd6c53
10.1371/journal.pcbi.1000210
Scopus Count
The following license files are associated with this item:
Related articles
- A genome-scale metabolic reconstruction of Pseudomonas putida KT2440: iJN746 as a cell factory.
- Authors: Nogales J, Palsson BØ, Thiele I
- Issue date: 2008 Sep 16
- Integrated analysis of gene expression and metabolic fluxes in PHA-producing Pseudomonas putida grown on glycerol.
- Authors: Beckers V, Poblete-Castro I, Tomasch J, Wittmann C
- Issue date: 2016 May 3
- In silico genome-scale metabolic analysis of Pseudomonas putida KT2440 for polyhydroxyalkanoate synthesis, degradation of aromatics and anaerobic survival.
- Authors: Sohn SB, Kim TY, Park JM, Lee SY
- Issue date: 2010 Jul
- Experimental validation of in silico estimated biomass yields of Pseudomonas putida KT2440.
- Authors: Hintermayer SB, Weuster-Botz D
- Issue date: 2017 Jun
- High-quality genome-scale metabolic modelling of Pseudomonas putida highlights its broad metabolic capabilities.
- Authors: Nogales J, Mueller J, Gudmundsson S, Canalejo FJ, Duque E, Monk J, Feist AM, Ramos JL, Niu W, Palsson BO
- Issue date: 2020 Jan