Metabolic perturbations in mutants of glucose transporters and their applications in metabolite production in Escherichia coli

Jung, Hwi Min; Im, Dae Kyun; Lim, Jae Hyung; Jung, Gyoo Yeol; Oh, Min Kyu

doi:10.1186/s12934-019-1224-8

Cited by 19 publications

(18 citation statements)

References 73 publications

(92 reference statements)

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“…In such a scenario, partially metabolized glucose would be discarded as acetate instead of complete processing through ATP-yielding respiratory reactions, with the accumulation of acetate and the lower ATP yield both negatively impacting biomass production relative to the non-glucose condition. This proposed explanation is consistent with reports that decreasing the glucose uptake rate can decrease occurrence of overflow metabolism (Jung et al 2019).…”

Section: Resultssupporting

confidence: 93%

Utilization of mechanocatalytic oligosaccharides by ethanologenic Escherichia coli as a model microbial cell factory

et al. 2020

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Mechanocatalysis is a promising method for depolymerization of lignocellulosic biomass. Microbial utilization of the resulting oligosaccharides is one potential route of adding value to the depolymerized biomass. However, it is unclear how readily these oligosaccharides are utilized by standard cell factories. Here, we investigate utilization of cellulose subjected to mechanocatalytic depolymerization, using ethanologenic Escherichia coli as a model fermentation organism. The mechanocatalytic oligosaccharides supported ethanol titers similar to those observed when glucose was provided at comparable concentrations. Tracking of the various oligomers, using maltose (alpha-1,4) and cellobiose (beta-1,4) oligomers as representative standards of the orientation, but not linkage, of the glycosidic bond, suggests that the malto-like-oligomers are more readily utilized than cello-like-oligomers, consistent with poor growth with cellotetraose or cellopentaose as sole carbon source. Thus, mechanocatalytic oligosaccharides are a promising substrate for cell factories, and microbial utilization of these sugars could possibly be improved by addressing utilization of cello-like oligomers.

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Section: Resultssupporting

confidence: 93%

Utilization of mechanocatalytic oligosaccharides by ethanologenic Escherichia coli as a model microbial cell factory

et al. 2020

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“…For an increase in product yield, the model indeed predicts the same shift in acetate overflow as for a decrease in growth yield (S2 Fig. ), consistent with reports in the literature [50].…”

Section: The Model Is Able To Reproduce Key Growth Phenotypessupporting

confidence: 89%

Enhanced production of heterologous proteins by a synthetic microbial community: Conditions and trade-offs

Mauri

Gouzé

Jong

et al. 2020

Preprint

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AbstractSynthetic microbial consortia have been increasingly utilized in biotechnology and experimental evidence shows that suitably engineered consortia can outperform individual species in the synthesis of valuable products. Despite significant achievements, though, a quantitative understanding of the conditions that make this possible, and of the trade-offs due to the concurrent growth of multiple species, is still limited. In this work, we contribute to filling this gap by the investigation of a known prototypical synthetic consortium. A first E. coli strain, producing a heterologous protein, is sided by a second E. coli strain engineered to scavenge toxic byproducts, thus favoring the growth of the producer at the expense of diverting part of the resources to the growth of the cleaner. The simplicity of the consortium is ideal to perform an in depth-analysis and draw conclusions of more general interest. We develop a coarse-grained mathematical model that quantitatively accounts for literature data from different key growth phenotypes. Based on this, assuming growth in chemostat, we first investigate the conditions enabling stable coexistence of both strains and the effect of the metabolic load due to heterologous protein production. In these conditions, we establish when and to what extent the consortium outperforms the producer alone in terms of productivity. Finally, we show in chemostat as well as in a fed-batch scenario that gain in productivity comes at the price of a reduced yield, reflecting at the level of the consortium resource allocation trade-offs that are well-known for individual species.

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“…Eq 13 shows that a glucose uptake rate equal to l occurs at lower D for both lower Y g (energy dissipation) and higher Y h (heterologous protein production). For an increase in product yield, the model indeed predicts the same shift in acetate overflow as for a decrease in growth yield (S2 Fig), consistent with reports in the literature [50]. Changes in growth rate and acetate secretion rate in glucose uptake mutants.…”

Section: Plos Computational Biologysupporting

confidence: 88%

Enhanced production of heterologous proteins by a synthetic microbial community: Conditions and trade-offs

et al. 2020

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Synthetic microbial consortia have been increasingly utilized in biotechnology and experimental evidence shows that suitably engineered consortia can outperform individual species in the synthesis of valuable products. Despite significant achievements, though, a quantitative understanding of the conditions that make this possible, and of the trade-offs due to the concurrent growth of multiple species, is still limited. In this work, we contribute to filling this gap by the investigation of a known prototypical synthetic consortium. A first E. coli strain, producing a heterologous protein, is sided by a second E. coli strain engineered to scavenge toxic byproducts, thus favoring the growth of the producer at the expense of diverting part of the resources to the growth of the cleaner. The simplicity of the consortium is ideal to perform an in depth-analysis and draw conclusions of more general interest. We develop a coarse-grained mathematical model that quantitatively accounts for literature data from different key growth phenotypes. Based on this, assuming growth in chemostat, we first investigate the conditions enabling stable coexistence of both strains and the effect of the metabolic load due to heterologous protein production. In these conditions, we establish when and to what extent the consortium outperforms the producer alone in terms of productivity. Finally, we show in chemostat as well as in a fed-batch scenario that gain in productivity comes at the price of a reduced yield, reflecting at the level of the consortium resource allocation trade-offs that are well-known for individual species.

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Metabolic perturbations in mutants of glucose transporters and their applications in metabolite production in Escherichia coli

Cited by 19 publications

References 73 publications

Utilization of mechanocatalytic oligosaccharides by ethanologenic Escherichia coli as a model microbial cell factory

Utilization of mechanocatalytic oligosaccharides by ethanologenic Escherichia coli as a model microbial cell factory

Enhanced production of heterologous proteins by a synthetic microbial community: Conditions and trade-offs

Enhanced production of heterologous proteins by a synthetic microbial community: Conditions and trade-offs

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