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Inducible Synthetic Growth Regulation Using the ClpXP Proteasome Enhances cis,cis-Muconic Acid and Glycolic Acid Yields in Saccharomyces cerevisiae
[Image: see text] Engineered microbial cells can produce sustainable chemistry, but the production competes for resources with growth. Inducible synthetic control over the resource use would enable fast accumulation of sufficient biomass and then divert the resources to production. We developed indu...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10127448/ https://www.ncbi.nlm.nih.gov/pubmed/36976676 http://dx.doi.org/10.1021/acssynbio.2c00467 |
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author | Kakko, Natalia Rantasalo, Anssi Koponen, Tino Vidgren, Virve Kannisto, Matti Maiorova, Natalia Nygren, Heli Mojzita, Dominik Penttilä, Merja Jouhten, Paula |
author_facet | Kakko, Natalia Rantasalo, Anssi Koponen, Tino Vidgren, Virve Kannisto, Matti Maiorova, Natalia Nygren, Heli Mojzita, Dominik Penttilä, Merja Jouhten, Paula |
author_sort | Kakko, Natalia |
collection | PubMed |
description | [Image: see text] Engineered microbial cells can produce sustainable chemistry, but the production competes for resources with growth. Inducible synthetic control over the resource use would enable fast accumulation of sufficient biomass and then divert the resources to production. We developed inducible synthetic resource-use control overSaccharomyces cerevisiae by expressing a bacterial ClpXP proteasome from an inducible promoter. By individually targeting growth-essential metabolic enzymes Aro1, Hom3, and Acc1 to the ClpXP proteasome, cell growth could be efficiently repressed during cultivation. The ClpXP proteasome was specific to the target proteins, and there was no reduction in the targets when ClpXP was not induced. The inducible growth repression improved product yields from glucose (cis,cis-muconic acid) and per biomass (cis,cis-muconic acid and glycolic acid). The inducible ClpXP proteasome tackles uncertainties in strain optimization by enabling model-guided repression of competing, growth-essential, and metabolic enzymes. Most importantly, it allows improving production without compromising biomass accumulation when uninduced; therefore, it is expected to mitigate strain stability and low productivity challenges. |
format | Online Article Text |
id | pubmed-10127448 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-101274482023-04-26 Inducible Synthetic Growth Regulation Using the ClpXP Proteasome Enhances cis,cis-Muconic Acid and Glycolic Acid Yields in Saccharomyces cerevisiae Kakko, Natalia Rantasalo, Anssi Koponen, Tino Vidgren, Virve Kannisto, Matti Maiorova, Natalia Nygren, Heli Mojzita, Dominik Penttilä, Merja Jouhten, Paula ACS Synth Biol [Image: see text] Engineered microbial cells can produce sustainable chemistry, but the production competes for resources with growth. Inducible synthetic control over the resource use would enable fast accumulation of sufficient biomass and then divert the resources to production. We developed inducible synthetic resource-use control overSaccharomyces cerevisiae by expressing a bacterial ClpXP proteasome from an inducible promoter. By individually targeting growth-essential metabolic enzymes Aro1, Hom3, and Acc1 to the ClpXP proteasome, cell growth could be efficiently repressed during cultivation. The ClpXP proteasome was specific to the target proteins, and there was no reduction in the targets when ClpXP was not induced. The inducible growth repression improved product yields from glucose (cis,cis-muconic acid) and per biomass (cis,cis-muconic acid and glycolic acid). The inducible ClpXP proteasome tackles uncertainties in strain optimization by enabling model-guided repression of competing, growth-essential, and metabolic enzymes. Most importantly, it allows improving production without compromising biomass accumulation when uninduced; therefore, it is expected to mitigate strain stability and low productivity challenges. American Chemical Society 2023-03-28 /pmc/articles/PMC10127448/ /pubmed/36976676 http://dx.doi.org/10.1021/acssynbio.2c00467 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Kakko, Natalia Rantasalo, Anssi Koponen, Tino Vidgren, Virve Kannisto, Matti Maiorova, Natalia Nygren, Heli Mojzita, Dominik Penttilä, Merja Jouhten, Paula Inducible Synthetic Growth Regulation Using the ClpXP Proteasome Enhances cis,cis-Muconic Acid and Glycolic Acid Yields in Saccharomyces cerevisiae |
title | Inducible Synthetic
Growth Regulation Using the ClpXP
Proteasome Enhances cis,cis-Muconic Acid and Glycolic Acid Yields
in Saccharomyces cerevisiae |
title_full | Inducible Synthetic
Growth Regulation Using the ClpXP
Proteasome Enhances cis,cis-Muconic Acid and Glycolic Acid Yields
in Saccharomyces cerevisiae |
title_fullStr | Inducible Synthetic
Growth Regulation Using the ClpXP
Proteasome Enhances cis,cis-Muconic Acid and Glycolic Acid Yields
in Saccharomyces cerevisiae |
title_full_unstemmed | Inducible Synthetic
Growth Regulation Using the ClpXP
Proteasome Enhances cis,cis-Muconic Acid and Glycolic Acid Yields
in Saccharomyces cerevisiae |
title_short | Inducible Synthetic
Growth Regulation Using the ClpXP
Proteasome Enhances cis,cis-Muconic Acid and Glycolic Acid Yields
in Saccharomyces cerevisiae |
title_sort | inducible synthetic
growth regulation using the clpxp
proteasome enhances cis,cis-muconic acid and glycolic acid yields
in saccharomyces cerevisiae |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10127448/ https://www.ncbi.nlm.nih.gov/pubmed/36976676 http://dx.doi.org/10.1021/acssynbio.2c00467 |
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