Genome-scale modeling enables metabolic engineering of Saccharomyces cerevisiae for succinic acid production
Artikel i vetenskaplig tidskrift, 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

Författare

Rasmus Ågren

Chalmers, Kemi- och bioteknik, Livsvetenskaper, Systembiologi

José Manuel Otero

Chalmers, Kemi- och bioteknik, Livsvetenskaper, Systembiologi

Jens B Nielsen

Chalmers, Kemi- och bioteknik, Livsvetenskaper, Systembiologi

Journal of Industrial Microbiology and Biotechnology

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

Vol. 40 7 735-747

Styrkeområden

Energi

Livsvetenskaper och teknik

Infrastruktur

C3SE (Chalmers Centre for Computational Science and Engineering)

Ämneskategorier

Mikrobiologi

Bioinformatik och systembiologi

DOI

10.1007/s10295-013-1269-3

Mer information

Skapat

2017-10-08