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- Title
A coupled thermodynamic and metabolic control analysis methodology and its evaluation on glycerol biosynthesis in Saccharomyces cerevisiae.
- Authors
Birkenmeier, Markus; Mack, Matthias; Röder, Thorsten
- Abstract
A coupled in silico thermodynamic and probabilistic metabolic control analysis methodology was verified by applying it to the glycerol biosynthetic pathway in Saccharomyces cerevisiae. The methodology allows predictions even when detailed knowledge of the enzyme kinetics is lacking. In a metabolic steady state, we found that glycerol-3-phosphate dehydrogenase operates far from thermodynamic equilibrium ( $$ \varDelta_{r} G^{\prime}_{1} $$ −15.9 to −47.5 kJ mol, where $$ \varDelta_{r} G^{\prime}_{1} $$ is the transformed Gibbs energy of the reaction). Glycerol-3-phosphataseoperates in modes near the thermodynamic equilibrium, far from the thermodynamic equilibrium or in between ( $$ \varDelta_{r} G^{\prime}_{2} $$ ≈ 0 to −23.7 kJ mol). From the calculated distribution of the scaled flux control coefficients (median = 0.81), we inferred that the pathway flux is primarily controlled by glycerol-3-phosphate dehydrogenase. This prediction is consistent with previous findings, verifying the efficacy of the proposed methodology.
- Subjects
METABOLIC regulation; SACCHAROMYCES cerevisiae; GLYCERIN; BIOSYNTHESIS; GLYCEROLPHOSPHATE dehydrogenase; THERMODYNAMIC equilibrium
- Publication
Biotechnology Letters, 2015, Vol 37, Issue 2, p307
- ISSN
0141-5492
- Publication type
Article
- DOI
10.1007/s10529-014-1675-2