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Metabolic Engineering Interventions for Sustainable 2,3-Butanediol Production in Gas-Fermenting Clostridium autoethanogenum
Gas fermentation provides a promising platform to turn low-cost and readily available single-carbon waste gases into commodity chemicals, such as 2,3-butanediol. Clostridium autoethanogenum is usually used as a robust and flexible chassis for gas fermentation. Here, we leveraged constraint-based sto...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9040633/ https://www.ncbi.nlm.nih.gov/pubmed/35323044 http://dx.doi.org/10.1128/msystems.01111-21 |
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author | Ghadermazi, Parsa Re, Angela Ricci, Luca Chan, Siu Hung Joshua |
author_facet | Ghadermazi, Parsa Re, Angela Ricci, Luca Chan, Siu Hung Joshua |
author_sort | Ghadermazi, Parsa |
collection | PubMed |
description | Gas fermentation provides a promising platform to turn low-cost and readily available single-carbon waste gases into commodity chemicals, such as 2,3-butanediol. Clostridium autoethanogenum is usually used as a robust and flexible chassis for gas fermentation. Here, we leveraged constraint-based stoichiometric modeling and kinetic ensemble modeling of the C. autoethanogenum metabolic network to provide a systematic in silico analysis of metabolic engineering interventions for 2,3-butanediol overproduction and low carbon substrate loss in dissipated CO(2). Our analysis allowed us to identify and to assess comparatively the expected performances for a wide range of single, double, and triple interventions. Our analysis managed to individuate bottleneck reactions in relevant metabolic pathways when suggesting intervening strategies. Besides recapitulating intuitive and/or previously attempted genetic modifications, our analysis neatly outlined that interventions—at least partially—impinging on by-products branching from acetyl coenzyme A (acetyl-CoA) and pyruvate (acetate, ethanol, amino acids) offer valuable alternatives to the interventions focusing directly on the specific branch from pyruvate to 2,3-butanediol. IMPORTANCE Envisioning value chains inspired by environmental sustainability and circularity in economic models is essential to counteract the alterations in the global natural carbon cycle induced by humans. Recycling carbon-based waste gas streams into chemicals by devising gas fermentation bioprocesses mediated by acetogens of the genus Clostridium is one component of the solution. Carbon monoxide originates from multiple biogenic and abiogenic sources and bears a significant environmental impact. This study aims at identifying metabolic engineering interventions for increasing 2,3-butanediol production and avoiding carbon loss in CO(2) dissipation via C. autoethanogenum fermenting a substrate comprising CO and H(2). 2,3-Butanediol is a valuable biochemical by-product since, due to its versatility, can be transformed quite easily into chemical compounds such as butadiene, diacetyl, acetoin, and methyl ethyl ketone. These compounds are usable as building blocks to manufacture a vast range of industrially produced chemicals. |
format | Online Article Text |
id | pubmed-9040633 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-90406332022-04-27 Metabolic Engineering Interventions for Sustainable 2,3-Butanediol Production in Gas-Fermenting Clostridium autoethanogenum Ghadermazi, Parsa Re, Angela Ricci, Luca Chan, Siu Hung Joshua mSystems Research Article Gas fermentation provides a promising platform to turn low-cost and readily available single-carbon waste gases into commodity chemicals, such as 2,3-butanediol. Clostridium autoethanogenum is usually used as a robust and flexible chassis for gas fermentation. Here, we leveraged constraint-based stoichiometric modeling and kinetic ensemble modeling of the C. autoethanogenum metabolic network to provide a systematic in silico analysis of metabolic engineering interventions for 2,3-butanediol overproduction and low carbon substrate loss in dissipated CO(2). Our analysis allowed us to identify and to assess comparatively the expected performances for a wide range of single, double, and triple interventions. Our analysis managed to individuate bottleneck reactions in relevant metabolic pathways when suggesting intervening strategies. Besides recapitulating intuitive and/or previously attempted genetic modifications, our analysis neatly outlined that interventions—at least partially—impinging on by-products branching from acetyl coenzyme A (acetyl-CoA) and pyruvate (acetate, ethanol, amino acids) offer valuable alternatives to the interventions focusing directly on the specific branch from pyruvate to 2,3-butanediol. IMPORTANCE Envisioning value chains inspired by environmental sustainability and circularity in economic models is essential to counteract the alterations in the global natural carbon cycle induced by humans. Recycling carbon-based waste gas streams into chemicals by devising gas fermentation bioprocesses mediated by acetogens of the genus Clostridium is one component of the solution. Carbon monoxide originates from multiple biogenic and abiogenic sources and bears a significant environmental impact. This study aims at identifying metabolic engineering interventions for increasing 2,3-butanediol production and avoiding carbon loss in CO(2) dissipation via C. autoethanogenum fermenting a substrate comprising CO and H(2). 2,3-Butanediol is a valuable biochemical by-product since, due to its versatility, can be transformed quite easily into chemical compounds such as butadiene, diacetyl, acetoin, and methyl ethyl ketone. These compounds are usable as building blocks to manufacture a vast range of industrially produced chemicals. American Society for Microbiology 2022-03-24 /pmc/articles/PMC9040633/ /pubmed/35323044 http://dx.doi.org/10.1128/msystems.01111-21 Text en Copyright © 2022 Ghadermazi et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Ghadermazi, Parsa Re, Angela Ricci, Luca Chan, Siu Hung Joshua Metabolic Engineering Interventions for Sustainable 2,3-Butanediol Production in Gas-Fermenting Clostridium autoethanogenum |
title | Metabolic Engineering Interventions for Sustainable 2,3-Butanediol Production in Gas-Fermenting Clostridium autoethanogenum |
title_full | Metabolic Engineering Interventions for Sustainable 2,3-Butanediol Production in Gas-Fermenting Clostridium autoethanogenum |
title_fullStr | Metabolic Engineering Interventions for Sustainable 2,3-Butanediol Production in Gas-Fermenting Clostridium autoethanogenum |
title_full_unstemmed | Metabolic Engineering Interventions for Sustainable 2,3-Butanediol Production in Gas-Fermenting Clostridium autoethanogenum |
title_short | Metabolic Engineering Interventions for Sustainable 2,3-Butanediol Production in Gas-Fermenting Clostridium autoethanogenum |
title_sort | metabolic engineering interventions for sustainable 2,3-butanediol production in gas-fermenting clostridium autoethanogenum |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9040633/ https://www.ncbi.nlm.nih.gov/pubmed/35323044 http://dx.doi.org/10.1128/msystems.01111-21 |
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