Optimal evaluation of energy yield and driving force in microbial metabolic pathway variants

Abstract

This work presents a methodology to evaluate the bioenergetic feasibility of alternative metabolic pathways for a given microbial conversion, optimising their energy yield and driving forces as a function of the concentration of metabolic intermediates. The tool, based on thermodynamic principles and multi-objective optimisation, accounts for pathway variants in terms of different electron carriers, as well as energy conservation (proton translocating) reactions within the pathway. The method also accommodates other constraints, some of them non-linear, such as the balance of conserved moieties. The approach involves the transformation of the maximum energy yield problem into a multi-objective linear optimisation problem which is then subsequently solved using the epsilon-constraint method, highlighting the trade-off between yield and rate in metabolic reactions. The methodology is applied to analyse several pathway alternatives occurring during propionate oxidation in anaerobic fermentation processes, as well as to the reverse TCA cycle pathway occurring during autotrophic microbial CO2 fixation. The results obtained using the developed methodology match previously reported literature, and bring about insights into the studied pathways.

Bioenergetic trade-offs can reveal the path to superior microbial CO2 fixation pathways

“…A recently developed, highly efficient, computational methodology by 44 allows for the analysis of a large number of pathway configuration variants and combines the maximisation of chemiosmotic energy yield, earlier explored in 45 , with the maximization of the minimum driving force (MDF). Through this methodology the exploration of the thermodynamic landscape quantifying the trade-offs between energy yield and rate for large numbers of metabolic pathway configurations is now within computational reach.…”