title: A coupled thermodynamic and metabolic control analysis methodology and its evaluation on glycerol biosynthesis in Saccharomyces cerevisiae.
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 ([Formula: see text] -15.9 to -47.5 kJ mol(-1), where [Formula: see text] 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 ([Formula: see text] ≈ 0 to -23.7 kJ mol(-1)). 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.
authors.affiliation: Institute for Chemical Process Engineering, Mannheim University of Applied Sciences, Paul-Wittsack-Straße 10, 68163, Mannheim, Germany, m.birkenmeier@hs-mannheim.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Birkenmeier
authors.forename: Matthias
authors.initials: M
authors.lastname: Mack
authors.forename: Thorsten
authors.initials: T
authors.lastname: Röder
mesh_terms: D001709:Biotechnology / Q000379:methods*; D003198:Computer Simulation; D005990:Glycerol / Q000378:metabolism*; D007700:Kinetics; D053858:Metabolic Networks and Pathways; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D005990:Glycerol