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Genome-scale modeling enables metabolic engineering of Saccharomyces cerevisiae for succinic acid production

Rasmus Ågren (Institutionen för kemi- och bioteknik, Systembiologi) ; José Manuel Otero Romero (Institutionen för kemi- och bioteknik, Systembiologi) ; Jens B. Nielsen (Institutionen för kemi- och bioteknik, Systembiologi)
Journal of Industrial Microbiology & Biotechnology (1367-5435). Vol. 40 (2013), 7, p. 735-747.
[Artikel, refereegranskad vetenskaplig]

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.

Nyckelord: Succinic acid, Metabolic engineering, Genome-scale modeling, DNA microarrays, Saccharomyces cerevisiae

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Denna post skapades 2013-08-02. Senast ändrad 2017-09-14.
CPL Pubid: 180442


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Institutioner (Chalmers)

Institutionen för kemi- och bioteknik, Systembiologi (2008-2014)


Bioinformatik och systembiologi

Chalmers infrastruktur

C3SE/SNIC (Chalmers Centre for Computational Science and Engineering)