Webinar: Interrogating the effect of enzyme kinetics on metabolism using constraint-based models
Channel: PerMedCoE
Date: 2023-02-23

Metabolic models are typically characterised by a large number of parameters. Traditionally, metabolic control analysis has been applied to differential equation-based models to investigate the sensitivity of predictions to parameters. A corresponding theory for constraint-based metabolic models is lacking due to their formulation as optimization problems. In this webinar we will show several applications of differentiating optimal solutions of constraint-based models, and show how it connects to classic metabolic control analysis. Efficient differentiation of constraint-based models can be used to calculate the sensitivities of predicted reaction fluxes and enzyme concentrations to turnover number parameters in an enzyme-constrained metabolic model of Escherichia coli. Further, it unlocks the ability to use gradient information for parameter estimation. We demonstrate this by improving, genome-wide, the state-of-the-art turnover number estimates for E. coli. Finally, this technique can be used to differentiate the optimal solution of a model incorporating both thermodynamic and kinetic rate equations. The predicted growth rate sensitivity to metabolite concentrations was shown to align well against experimentally measured metabolome changes subject to gene knockouts.

Speakers: Dr St. Elmo Wilken, Heinrich Heine University (Germany)
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