A metabolic reconstruction of Lactobacillus reuteri JCM 1112 and analysis of its potential as a cell factory

Kristjansdottir, T.; Bosma, E. F.; Santos, F.; Özdemir, E.; Herrgard, M. J.; Franca, L.; Ferreira, B. S.; Nielsen, A. T.; Guđmundsson, S.

doi:10.1101/708875

bioRxiv · 10.1101/708875

A metabolic reconstruction of Lactobacillus reuteri JCM 1112 and analysis of its potential as a cell factory

Kristjansdottir, T.·Bosma, E. F.·Santos, F.·Özdemir, E.·Herrgard, M. J.·Franca, L.·Ferreira, B. S.·Nielsen, A. T.·Guđmundsson, S.

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Abstract

BackgroundLactobacillus 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.\n\nResultsA 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.\n\nConclusionWe 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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Kristjansdottir, T., Bosma, E. F., Santos, F., Özdemir, E., Herrgard, M. J., Franca, L., Ferreira, B. S., Nielsen, A. T., Guđmundsson, S.. 2019-08-01. A metabolic reconstruction of Lactobacillus reuteri JCM 1112 and analysis of its potential as a cell factory. https://doi.org/10.1101/708875

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