論文 - 詳細
| RRC ID | 60586 |
|---|---|
| 著者 | Kristjansdottir T, Bosma EF, Branco Dos Santos F, Özdemir E, Herrgård MJ, França L, Ferreira B, Nielsen AT, Gudmundsson S. |
| タイトル | A metabolic reconstruction of Lactobacillus reuteri JCM 1112 and analysis of its potential as a cell factory. |
| ジャーナル | Microb Cell Fact |
| 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. |
| 巻・号 | 18(1) |
| ページ | 186 |
| 公開日 | 2019-10-29 |
| DOI | 10.1186/s12934-019-1229-3 |
| PII | 10.1186/s12934-019-1229-3 |
| PMID | 31665018 |
| PMC | PMC6821008 |
| MeSH | Fermentation Limosilactobacillus reuteri* / genetics Limosilactobacillus reuteri* / growth & development Limosilactobacillus reuteri* / metabolism Metabolic Engineering* Probiotics / metabolism* |
| IF | 4.187 |
| リソース情報 | |
| 一般微生物 | JCM1112 |