Theoretical investigation of a genetic switch for metabolic adaptation.
Membrane transporters carry key metabolites across the cell membrane and, from a resource standpoint, are hypothesized to be produced when necessary. The expression of membrane transporters in metabolic pathways is often upregulated by the transporter substrate. In E. coli, such systems include for...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0226453 |
| _version_ | 1797788246482092032 |
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| author | Kathrin S Laxhuber Muir J Morrison Griffin Chure Nathan M Belliveau Charlotte Strandkvist Kyle L Naughton Rob Phillips |
| author_facet | Kathrin S Laxhuber Muir J Morrison Griffin Chure Nathan M Belliveau Charlotte Strandkvist Kyle L Naughton Rob Phillips |
| author_sort | Kathrin S Laxhuber |
| collection | DOAJ |
| description | Membrane transporters carry key metabolites across the cell membrane and, from a resource standpoint, are hypothesized to be produced when necessary. The expression of membrane transporters in metabolic pathways is often upregulated by the transporter substrate. In E. coli, such systems include for example the lacY, araFGH, and xylFGH genes, which encode for lactose, arabinose, and xylose transporters, respectively. As a case study of a minimal system, we build a generalizable physical model of the xapABR genetic circuit, which features a regulatory feedback loop via membrane transport (positive feedback) and enzymatic degradation (negative feedback) of an inducer. Dynamical systems analysis and stochastic simulations show that the membrane transport makes the model system bistable in certain parameter regimes. Thus, it serves as a genetic "on-off" switch, enabling the cell to only produce a set of metabolic enzymes when the corresponding metabolite is present in large amounts. We find that the negative feedback from the degradation enzyme does not significantly disturb the positive feedback from the membrane transporter. We investigate hysteresis in the switching and discuss the role of cooperativity and multiple binding sites in the model circuit. Fundamentally, this work explores how a stable genetic switch for a set of enzymes is obtained from transcriptional auto-activation of a membrane transporter through its substrate. |
| first_indexed | 2024-03-13T01:32:54Z |
| format | Article |
| id | doaj.art-5333eb7e46904c15b7d46fd347b82502 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-13T01:32:54Z |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-5333eb7e46904c15b7d46fd347b825022023-07-04T05:32:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01155e022645310.1371/journal.pone.0226453Theoretical investigation of a genetic switch for metabolic adaptation.Kathrin S LaxhuberMuir J MorrisonGriffin ChureNathan M BelliveauCharlotte StrandkvistKyle L NaughtonRob PhillipsMembrane transporters carry key metabolites across the cell membrane and, from a resource standpoint, are hypothesized to be produced when necessary. The expression of membrane transporters in metabolic pathways is often upregulated by the transporter substrate. In E. coli, such systems include for example the lacY, araFGH, and xylFGH genes, which encode for lactose, arabinose, and xylose transporters, respectively. As a case study of a minimal system, we build a generalizable physical model of the xapABR genetic circuit, which features a regulatory feedback loop via membrane transport (positive feedback) and enzymatic degradation (negative feedback) of an inducer. Dynamical systems analysis and stochastic simulations show that the membrane transport makes the model system bistable in certain parameter regimes. Thus, it serves as a genetic "on-off" switch, enabling the cell to only produce a set of metabolic enzymes when the corresponding metabolite is present in large amounts. We find that the negative feedback from the degradation enzyme does not significantly disturb the positive feedback from the membrane transporter. We investigate hysteresis in the switching and discuss the role of cooperativity and multiple binding sites in the model circuit. Fundamentally, this work explores how a stable genetic switch for a set of enzymes is obtained from transcriptional auto-activation of a membrane transporter through its substrate.https://doi.org/10.1371/journal.pone.0226453 |
| spellingShingle | Kathrin S Laxhuber Muir J Morrison Griffin Chure Nathan M Belliveau Charlotte Strandkvist Kyle L Naughton Rob Phillips Theoretical investigation of a genetic switch for metabolic adaptation. PLoS ONE |
| title | Theoretical investigation of a genetic switch for metabolic adaptation. |
| title_full | Theoretical investigation of a genetic switch for metabolic adaptation. |
| title_fullStr | Theoretical investigation of a genetic switch for metabolic adaptation. |
| title_full_unstemmed | Theoretical investigation of a genetic switch for metabolic adaptation. |
| title_short | Theoretical investigation of a genetic switch for metabolic adaptation. |
| title_sort | theoretical investigation of a genetic switch for metabolic adaptation |
| url | https://doi.org/10.1371/journal.pone.0226453 |
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