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

• Published in: PLoS computational biology Vol. 19; no. 7; p. e1011264
• Main Authors: Taha, Ahmed, Patón, Mauricio, Penas, David R, Banga, Julio R, Rodríguez, Jorge
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.07.2023
• Subjects: Anaerobic processes; Analysis; Biology and Life Sciences; Carbon dioxide; Carbon dioxide fixation; Citric Acid Cycle; Energy conservation; Energy efficiency; Energy Metabolism; Enzymes; Fermentation; Funding; Integer programming; Intermediates; Mathematical optimization; Metabolic Networks and Pathways; Metabolic pathways; Metabolism; Metabolites; Methodology; Methods; Microbial metabolism; Microbiological research; Microorganisms; Mixed integer; Multiple objective analysis; Optimization; Oxidation; Physical Sciences; Thermodynamics; Tricarboxylic acid cycle; Spain
• ISSN: 1553-7358; 1553-734X; 1553-7358
• DOI: 10.1371/journal.pcbi.1011264

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 mixed-integer 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.