Genome-scale modeling enables metabolic engineering of Saccharomyces cerevisiae for succinic acid production
Journal article, 2013

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.

DNA microarrays

Saccharomyces cerevisiae

Succinic acid

Metabolic engineering

Genome-scale modeling

Author

Rasmus Ågren

Chalmers, Chemical and Biological Engineering, Life Sciences, System Biology

José Manuel Otero

Chalmers, Chemical and Biological Engineering, Life Sciences, System Biology

Jens B Nielsen

Chalmers, Chemical and Biological Engineering, Life Sciences, System Biology

Journal of Industrial Microbiology and Biotechnology

1367-5435 (ISSN) 1476-5535 (eISSN)

Vol. 40 7 735-747

Areas of Advance

Energy

Life Science Engineering (2010-2018)

Infrastructure

C3SE (Chalmers Centre for Computational Science and Engineering)

Subject Categories

Microbiology

Bioinformatics and Systems Biology

DOI

10.1007/s10295-013-1269-3

More information

Created

10/8/2017