Projects per year
Abstract
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.
Original language | English |
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Pages (from-to) | 1021–1033 |
Journal | ACS Synthetic Biology |
Volume | 12 |
Issue number | 4 |
Early online date | 28 Mar 2023 |
DOIs | |
Publication status | Published - 21 Apr 2023 |
MoE publication type | A1 Journal article-refereed |
Keywords
- cis,cis-muconic acid
- ClpXP proteasome
- glycolic acid
- Saccharomyces cerevisiae
- synthetic regulation
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Dive into the research topics of 'Inducible Synthetic Growth Regulation Using the ClpXP Proteasome Enhances cis,cis-Muconic Acid and Glycolic Acid Yields in Saccharomyces cerevisiae'. Together they form a unique fingerprint.Projects
- 2 Finished
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Modulation of resource distribution in cells
Jouhten, P. (Principal investigator)
01/01/2022 → 31/08/2022
Project: Academy of Finland: Other research funding
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Jouhten Paula AT-kulut: Modulation of resource distribution in cells/Tutkimuskulut
Jouhten, P. (Principal investigator), Mekki, C. (Project Member), Porri, L. (Project Member), Määttä, T. (Project Member), de Lucena Antunes, D. (Project Member) & Strucko, T. (Project Member)
01/01/2022 → 30/06/2023
Project: Academy of Finland: Other research funding