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Rewiring Saccharomy...
Rewiring Saccharomyces cerevisiae metabolism for optimised Taxol® precursors production
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- Nowrouzi, Behnaz (author)
- Danmarks Tekniske Universitet,Technical University of Denmark,Chalmers tekniska högskola,Chalmers University of Technology,University of Edinburgh
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- Torres-Montero, Pablo (author)
- Danmarks Tekniske Universitet,Technical University of Denmark
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- Kerkhoven, Eduard, 1985 (author)
- Novo Nordisk Fonden,Novo Nordisk Foundation,Chalmers tekniska högskola,Chalmers University of Technology
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- Martinez Ruiz, Jose Luis, 1981 (author)
- Danmarks Tekniske Universitet,Technical University of Denmark
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- Rios-Solis, Leonardo (author)
- University of Edinburgh,University of Newcastle upon Tyne,University College London (UCL)
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(creator_code:org_t)
- 2024
- 2024
- English.
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In: Metabolic Engineering Communications. - 2214-0301. ; 18
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https://doi.org/10.1...
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Abstract
Subject headings
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- Saccharomyces cerevisiae has been conveniently used to produce Taxol® anticancer drug early precursors. However, the harmful impact of oxidative stress by the first cytochrome P450-reductase enzymes (CYP725A4-POR) of Taxol® pathway has hampered sufficient progress in yeast. Here, we evolved an oxidative stress-resistant yeast strain with three-fold higher titre of their substrate, taxadiene. The performance of the evolved and parent strains were then evaluated in galactose-limited chemostats before and under the oxidative stress by an oxidising agent. The interaction of evolution and oxidative stress was comprehensively evaluated through transcriptomics and metabolite profiles integration in yeast enzyme-constrained genome scale model. Overall, the evolved strain showed improved respiration, reduced overflow metabolites production and oxidative stress re-induction tolerance. The cross-protection mechanism also potentially contributed to better heme, flavin and NADPH availability, essential for CYP725A4 and POR optimal activity in yeast. The results imply that the evolved strain is a robust cell factory for future efforts towards Taxol© production.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Mikrobiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Microbiology (hsv//eng)
Keyword
- Saccharomyces cerevisiae
- Oxidative stress
- Adaptive laboratory evolution
- Taxadiene
- Taxol®
Publication and Content Type
- art (subject category)
- ref (subject category)
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