Disentangling Intracellular Behavior from Extracellular Data*

Bacteria can utilize a biodiesel waste product, glycerol, to produce 1,3-propanediol (1,3-PDO), a common commercial solvent. To study the viability of 1,3-PDO producing bacteria, the cell membrane transport of reactant species and the in-vivo kinetics of the pathway enzymes (DhaT & DhaB) need to be quantified. The kinetics of purified DhaT have been studied, but the reaction environment and kinetics in cells may differ. Additionally, the kinetics of the DhaB enzyme and cell membrane transport mechanisms of the reactants are undetermined. 

With published consumption and production time series data of bacteria feeding on different initial glycerol concentrations, I used Bayesian inference on a differential equation model of the system to infer the unknown parameters.  The resulting data distribution closely matched the experimental results. The resulting parameter distributions revealed that glycerol and 1,3-PDO are transported via facilitated diffusion; the maximum reaction rate of DhaT is larger in-vivo than in-vitro; and the permeability of 3-HPA, a toxic intermediate, is structurally unidentifiable under the experimental conditions.