Academic Journal
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 |
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| Authors: | Kakko, Natalia, Rantasalo, Anssi, Koponen, Tino, Vidgren, Virve, Kannisto, Matti, Maiorova, Natalia, Nygren, Heli, Mojzita, Dominik, Penttilä, Merja, Jouhten, Paula |
| Superior Title: | ACS Synth Biol |
| Publisher Information: | American Chemical Society |
| Publication Year: | 2023 |
| Collection: | PubMed Central (PMC) |
| 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. |
| Document Type: | text |
| Language: | English |
| Relation: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10127448/; http://www.ncbi.nlm.nih.gov/pubmed/36976676; http://dx.doi.org/10.1021/acssynbio.2c00467 |
| DOI: | 10.1021/acssynbio.2c00467 |
| Availability: | https://doi.org/10.1021/acssynbio.2c00467 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10127448/ http://www.ncbi.nlm.nih.gov/pubmed/36976676 |
| Rights: | © 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/). |
| Accession Number: | edsbas.C7E89DD7 |
| Database: | BASE |
| Description not available. |