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Regulatory control circuits for stabilizing long-term anabolic product formation in yeast.
D'Ambrosio, Vasil; Dore, Eleonora; Di Blasi, Roberto; van den Broek, Marcel; Sudarsan, Suresh; Horst, Jolanda Ter; Ambri, Francesca; Sommer, Morten O A; Rugbjerg, Peter; Keasling, Jay D; Mans, Robert; Jensen, Michael K.
Afiliación
  • D'Ambrosio V; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs, Lyngby, Denmark.
  • Dore E; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs, Lyngby, Denmark.
  • Di Blasi R; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs, Lyngby, Denmark.
  • van den Broek M; Department of Biotechnology, Delft University of Technology, Delft, the Netherlands.
  • Sudarsan S; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs, Lyngby, Denmark.
  • Horst JT; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs, Lyngby, Denmark.
  • Ambri F; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs, Lyngby, Denmark.
  • Sommer MOA; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs, Lyngby, Denmark.
  • Rugbjerg P; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs, Lyngby, Denmark.
  • Keasling JD; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs, Lyngby, Denmark; Joint BioEnergy Institute, Emeryville, CA, USA; Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA; Department of Chemical and Biomolecular
  • Mans R; Department of Biotechnology, Delft University of Technology, Delft, the Netherlands. Electronic address: R.Mans@tudelft.nl.
  • Jensen MK; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs, Lyngby, Denmark. Electronic address: mije@biosustain.dtu.dk.
Metab Eng ; 61: 369-380, 2020 09.
Article en En | MEDLINE | ID: mdl-32717328
Engineering living cells for production of chemicals, enzymes and therapeutics can burden cells due to use of limited native co-factor availability and/or expression burdens, totalling a fitness deficit compared to parental cells encoded through long evolutionary trajectories to maximise fitness. Ultimately, this discrepancy puts a selective pressure against fitness-burdened engineered cells under prolonged bioprocesses, and potentially leads to complete eradication of high-performing engineered cells at the population level. Here we present the mutation landscapes of fitness-burdened yeast cells engineered for vanillin-ß-glucoside production. Next, we design synthetic control circuits based on transcriptome analysis and biosensors responsive to vanillin-ß-glucoside pathway intermediates in order to stabilize vanillin-ß-glucoside production over ~55 generations in sequential passage experiments. Furthermore, using biosensors with two different modes of action we identify control circuits linking vanillin-ß-glucoside pathway flux to various essential cellular functions, and demonstrate control circuits robustness and almost 2-fold higher vanillin-ß-glucoside production, including 5-fold increase in total vanillin-ß-glucoside pathway metabolite accumulation, in a fed-batch fermentation compared to vanillin-ß-glucoside producing cells without control circuits.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Saccharomyces cerevisiae / Benzaldehídos / Regulación Fúngica de la Expresión Génica / Transcriptoma Tipo de estudio: Prognostic_studies Idioma: En Revista: Metab Eng Asunto de la revista: ENGENHARIA BIOMEDICA / METABOLISMO Año: 2020 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Bélgica
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Saccharomyces cerevisiae / Benzaldehídos / Regulación Fúngica de la Expresión Génica / Transcriptoma Tipo de estudio: Prognostic_studies Idioma: En Revista: Metab Eng Asunto de la revista: ENGENHARIA BIOMEDICA / METABOLISMO Año: 2020 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Bélgica