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Genome-scale modeling enables metabolic engineering of Saccharomyces cerevisiae for succinic acid production
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- Ågren, Rasmus, 1982 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Otero, José Manuel, 1979 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Nielsen, Jens B, 1962 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
- (creator_code:org_t)
- 2013-07-01
- 2013
- English.
- In: Journal of Industrial Microbiology and Biotechnology. - : Oxford University Press (OUP). - 1367-5435 .- 1476-5535. ; 40:7, s. 735-747
- Journal article (peer-reviewed)
Abstract
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- In this work, we describe the application of a genome-scale metabolic model and flux balance analysis for the prediction of succinic acid overproduction strategies in Saccharomyces cerevisiae. The top three single gene deletion strategies, Delta mdh1, Delta oac1, and Delta dic1, were tested using knock-out strains cultivated anaerobically on glucose, coupled with physiological and DNA microarray characterization. While Delta mdh1 and Delta oac1 strains failed to produce succinate, Delta dic1 produced 0.02 C-mol/C-mol glucose, in close agreement with model predictions (0.03 C-mol/C-mol glucose). Transcriptional profiling suggests that succinate formation is coupled to mitochondrial redox balancing, and more specifically, reductive TCA cycle activity. While far from industrial titers, this proof-of-concept suggests that in silico predictions coupled with experimental validation can be used to identify novel and non-intuitive metabolic engineering strategies.
Subject headings
- NATURVETENSKAP -- Biologi -- Mikrobiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Microbiology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Bioinformatik och systembiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Bioinformatics and Systems Biology (hsv//eng)
Keyword
- DNA microarrays
- Saccharomyces cerevisiae
- Succinic acid
- Metabolic engineering
- Genome-scale modeling
Publication and Content Type
- art (subject category)
- ref (subject category)
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