Genome-scale metabolic modeling of P. thermoglucosidasius NCIMB 11955 reveals metabolic bottlenecks in anaerobic metabolism

Mol, Viviënne; Bennett, Martyn; Sánchez, Benjamín J.; Lisowska, Beata K; Nielsen, Alex Toftgaard; Leak, David J.; Sonnenschein, Nikolaus

doi:10.1016/j.ymben.2021.03.002

Cited by 15 publications

(9 citation statements)

References 88 publications

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“…Upon analysis of biosynthesis pathways in iGEL604 , a possible vitamin B12 auxotrophy was discovered. In Parageobacillus thermoglucosidasius NCIMB 11955 a hybrid pathway of vitamin B12 biosynthesis has been suggested ( Mol et al, 2021 ), where enzymes from the anaerobic pathway can perform the reaction steps where the aerobic enzymes are missing and vice versa. However, the enzymes converting precorrin 4 to precorrin 5 (CbiF/CobM), precorrin 6A to precorrin 6B (CbiJ/CobK), and adenosyl cobyrinate diamide to adenosyl cobyrinate hexaamide (CbiP/CobQ) are either missing or found wdisrupted in both the aerobic and anaerobic branch in the LC300 genome.…”

Section: Discussionmentioning

confidence: 99%

“…Since the majority of characterized enzymes stem from mesophilic organisms, assigning thermophilic protein sequences can thus be problematic. Despite these difficulties several GEMs of thermophilic organisms exist, including Clostridium thermocellum ( Thompson et al, 2016 ; Garcia et al, 2020 ), Parageobacillus thermoglucosidasius ( Ahmad et al, 2017 ; Mol et al, 2021 ) and Geobacillus iciganus ( Kulyashov et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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Genome-scale reconstruction and metabolic modelling of the fast-growing thermophile Geobacillus sp. LC300

Ljungqvist

Gustavsson

2022

Metabolic Engineering Communications

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genome-scale reconstruction and metabolic modelling of the fast-growing thermophile Geobacillus sp. LC300

Ljungqvist

Gustavsson

2022

Metabolic Engineering Communications

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“…Visualisation of the data was performed with R Studio (Additional file 3: Fig S4 -S8). The R script was based on work by Mol et al [74].…”

Section: Constraint-based Flux Analysismentioning

confidence: 99%

High-quality genome-scale metabolic network reconstruction of probiotic bacterium Escherichia coli Nissle 1917

et al. 2022

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Background Escherichia coli Nissle 1917 (EcN) is a probiotic bacterium used to treat various gastrointestinal diseases. EcN is increasingly being used as a chassis for the engineering of advanced microbiome therapeutics. To aid in future engineering efforts, our aim was to construct an updated metabolic model of EcN with extended secondary metabolite representation. Results An updated high-quality genome-scale metabolic model of EcN, iHM1533, was developed based on comparison with 55 E. coli/Shigella reference GEMs and manual curation, including expanded secondary metabolite pathways (enterobactin, salmochelins, aerobactin, yersiniabactin, and colibactin). The model was validated and improved using phenotype microarray data, resulting in an 82.3% accuracy in predicting growth phenotypes on various nutrition sources. Flux variability analysis with previously published 13C fluxomics data validated prediction of the internal central carbon fluxes. A standardised test suite called Memote assessed the quality of iHM1533 to have an overall score of 89%. The model was applied by using constraint-based flux analysis to predict targets for optimisation of secondary metabolite production. Modelling predicted design targets from across amino acid metabolism, carbon metabolism, and other subsystems that are common or unique for influencing the production of various secondary metabolites. Conclusion iHM1533 represents a well-annotated metabolic model of EcN with extended secondary metabolite representation. Phenotype characterisation and the iHM1533 model provide a better understanding of the metabolic capabilities of EcN and will help future metabolic engineering efforts.

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“…Further support for the occurrence of the CO interaction with terminal oxidases in P. thermoglucosidasius is provided by the absence of the above metabolic shift under anaerobic conditions. This shift results in faster glucose consumption under initial aerobic conditions as pyruvate and Acetyl-CoA pools get converted in one or two steps to lactate, and acetate, rather than going through several additional conversions in the TCA cycle [34,42]. However, this implicates the disadvantage of lower total ATP production since acid fermentation yields less ATP per mole of glucose [43].…”

Section: Carbon Monoxide Induced Rerouting Of Carbon Flux During Init...mentioning

confidence: 99%

Thermophilic Water Gas Shift Reaction at High Carbon Monoxide and Hydrogen Partial Pressures in Parageobacillus thermoglucosidasius KP1013

2022

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The facultatively anaerobic Parageobacillus thermoglucosidasius oxidizes carbon monoxide to produce hydrogen via the water gas shift (WGS) reaction. In the current work, we examined the influence of carbon monoxide (CO) and hydrogen (H2) on the WGS reaction in the thermophilic P. thermoglucosidasius by cultivating two hydrogenogenic strains under varying CO and H2 compositions. Microbial growth and dynamics of the WGS reaction were monitored by evaluating parameters such as pressure, headspace composition, metabolic intermediates, pH, and optical density. Our analyses revealed that compared to the previously studied P. thermoglucosidasius strains, the strain KP1013 demonstrated higher CO tolerance and improved WGS reaction kinetics. Under anaerobic conditions, the lag phase before the WGS reaction shortened to 8 h, with KP1013 showing no hydrogen-induced product inhibition at hydrogen partial pressures up to 1.25 bar. The observed lack of product inhibition and the reduced lag phase of the WGS reaction support the possibility of establishing an industrial process for biohydrogen production with P. thermoglucosidasius.

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Genome-scale metabolic modeling of P. thermoglucosidasius NCIMB 11955 reveals metabolic bottlenecks in anaerobic metabolism

Cited by 15 publications

References 88 publications

Genome-scale reconstruction and metabolic modelling of the fast-growing thermophile Geobacillus sp. LC300

Genome-scale reconstruction and metabolic modelling of the fast-growing thermophile Geobacillus sp. LC300

High-quality genome-scale metabolic network reconstruction of probiotic bacterium Escherichia coli Nissle 1917

Thermophilic Water Gas Shift Reaction at High Carbon Monoxide and Hydrogen Partial Pressures in Parageobacillus thermoglucosidasius KP1013

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