Dynamic Enzyme-Cost Flux Balance Analysis (deFBA) Modelling for an Industrially Relevant Methanotroph Methylomicrobium Buryatense

Constraint-based modelling has made significant progress in the last few years. Starting from metabolic network reconstructions a whole range of different modelling frameworks has been developed. The static flux balance analysis (FBA) method allows calculation of intracellular and exchange fluxes. Mahadevan et al. (2002) extended this approach to predict dynamic concentration profiles of extracellular metabolites, the so-called dynamic flux balance analysis method (DFBA). Recently, Waldherr et al. (2015) developed the dynamic enzyme-cost flux balance analysis (deFBA) framework. This approach includes enzyme production and takes into account that reaction fluxes are limited by the amount of catalyzing enzyme present inside the cells.

In this contribution, the construction of a deFBA model for the methanotroph Methylomicrobium buryatense is discussed. M. buryatense consumes methane and produces small organic acids. The deFBA model is built starting from a metabolic network reconstruction from de la Torre et al. (2015). Enzyme composition and catalytic information are obtained from online databases such as BRENDA, Kegg, GenBank and Uniprot. A deFBA model is obtained containing 546 reactions from which 149 are enzyme production reactions. The model simulations predict specific substrate uptake and growth rates comparable to experimentally obtained values by Gilman et al. (2015). An exponential growth profile for biomass and its components is predicted. Production fluxes for acetic and formic acid are non-zero. However, lactic acid is not produced which contradicts experimental measurements.

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