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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...

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Autores principales: Kakko, Natalia, Rantasalo, Anssi, Koponen, Tino, Vidgren, Virve, Kannisto, Matti, Maiorova, Natalia, Nygren, Heli, Mojzita, Dominik, Penttilä, Merja, Jouhten, Paula
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
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.
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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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