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Designing an irreversible metabolic switch for scalable induction of microbial chemical production
Bacteria can be harnessed to synthesise high-value chemicals. A promising strategy for increasing productivity uses inducible control systems to switch metabolism from growth to chemical synthesis once a large population of cell factories are generated. However, use of expensive chemical inducers li...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187666/ https://www.ncbi.nlm.nih.gov/pubmed/34103495 http://dx.doi.org/10.1038/s41467-021-23606-x |
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author | Mannan, Ahmad A. Bates, Declan G. |
author_facet | Mannan, Ahmad A. Bates, Declan G. |
author_sort | Mannan, Ahmad A. |
collection | PubMed |
description | Bacteria can be harnessed to synthesise high-value chemicals. A promising strategy for increasing productivity uses inducible control systems to switch metabolism from growth to chemical synthesis once a large population of cell factories are generated. However, use of expensive chemical inducers limits scalability of this approach for biotechnological applications. Switching using cheap nutrients is an appealing alternative, but their tightly regulated uptake and consumption again limits scalability. Here, using mathematical models of fatty acid uptake in E. coli as an exemplary case study, we unravel how the cell’s native regulation and program of induction can be engineered to minimise inducer usage. We show that integrating positive feedback loops into the circuitry creates an irreversible metabolic switch, which, requiring only temporary induction, drastically reduces inducer usage. Our proposed switch should be widely applicable, irrespective of the product of interest, and brings closer the realization of scalable and sustainable microbial chemical production. |
format | Online Article Text |
id | pubmed-8187666 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-81876662021-07-01 Designing an irreversible metabolic switch for scalable induction of microbial chemical production Mannan, Ahmad A. Bates, Declan G. Nat Commun Article Bacteria can be harnessed to synthesise high-value chemicals. A promising strategy for increasing productivity uses inducible control systems to switch metabolism from growth to chemical synthesis once a large population of cell factories are generated. However, use of expensive chemical inducers limits scalability of this approach for biotechnological applications. Switching using cheap nutrients is an appealing alternative, but their tightly regulated uptake and consumption again limits scalability. Here, using mathematical models of fatty acid uptake in E. coli as an exemplary case study, we unravel how the cell’s native regulation and program of induction can be engineered to minimise inducer usage. We show that integrating positive feedback loops into the circuitry creates an irreversible metabolic switch, which, requiring only temporary induction, drastically reduces inducer usage. Our proposed switch should be widely applicable, irrespective of the product of interest, and brings closer the realization of scalable and sustainable microbial chemical production. Nature Publishing Group UK 2021-06-08 /pmc/articles/PMC8187666/ /pubmed/34103495 http://dx.doi.org/10.1038/s41467-021-23606-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Mannan, Ahmad A. Bates, Declan G. Designing an irreversible metabolic switch for scalable induction of microbial chemical production |
title | Designing an irreversible metabolic switch for scalable induction of microbial chemical production |
title_full | Designing an irreversible metabolic switch for scalable induction of microbial chemical production |
title_fullStr | Designing an irreversible metabolic switch for scalable induction of microbial chemical production |
title_full_unstemmed | Designing an irreversible metabolic switch for scalable induction of microbial chemical production |
title_short | Designing an irreversible metabolic switch for scalable induction of microbial chemical production |
title_sort | designing an irreversible metabolic switch for scalable induction of microbial chemical production |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187666/ https://www.ncbi.nlm.nih.gov/pubmed/34103495 http://dx.doi.org/10.1038/s41467-021-23606-x |
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