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Enhancing sesquiter...
Enhancing sesquiterpene production in Saccharomyces cerevisiae through in silico driven metabolic engineering
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Asadollahi, M. A. (författare)
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Maury, J. (författare)
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Patil, K. R. (författare)
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Schalk, M. (författare)
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Clark, A. (författare)
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- Nielsen, Jens B, 1962 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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(creator_code:org_t)
- Elsevier BV, 2009
- 2009
- Engelska.
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Ingår i: Metabolic Engineering. - : Elsevier BV. - 1096-7176 .- 1096-7184. ; 11:6, s. 328-334
- Relaterad länk:
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http://dx.doi.org/10...
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https://doi.org/10.1...
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https://research.cha...
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Abstract
Ämnesord
Stäng
- A genome-scale metabolic model was used to identify new target genes for enhanced biosynthesis of sesquiterpenes in the yeast Saccharomyces cerevisiae. The effect of gene deletions on the flux distributions in the metabolic model of S. cerevisiae was assessed using Opt Gene as the modeling framework and minimization of metabolic adjustments (MOMA) as objective function. Deletion of NADPH-dependent glutamate dehydrogenase encoded by GDH1 was identified as the best target gene for the improvement of sesquiterpene biosynthesis in yeast. Deletion of this gene enhances the available NADPH in the cytosol for other NADPH requiring enzymes, including HMG-CoA reductase. However, since disruption of GDH1 impairs the ammonia utilization, simultaneous over-expression of the NADH-dependent glutamate dehydrogenase en coded by GDH2 was also considered in this study. Deletion of GDH1 led to an approximately 85% increase in the final cubebol titer. However, deletion of this gene also caused a significant decrease in the maximum specific growth rate. Over-expression of GDH2 did not show a further effect on the final cubebol titer but this alteration significantly improved the growth rate compared to the GDH1 deleted strain. (C) 2009 Elsevier Inc. All rights reserved.
Ämnesord
- NATURVETENSKAP -- Biologi -- Mikrobiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Microbiology (hsv//eng)
Nyckelord
- beta-carotene
- food yeast
- biosynthesis
- Saccharomyces cerevisiae
- Sesquiterpene
- Isoprenoid
- yeast candida-utilis
- Glutamate dehydrogenase
- ammonium
- high-level production
- assimilation
- glutamate-dehydrogenase
- lycopene
- escherichia-coli
- catabolite repression
- NADPH availability
- Minimization of metabolic adjustments
- Flux balance analysis
- Cubebol
- In silico metabolic engineering
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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