Department of Chemical Engineering, Research and Innovation Center on CO2 and H2 (RICH) Khalifa University, Abu Dhabi, United Arab Emirates.
Computational Biology Lab, MBG-CSIC (Spanish National Research Council), Pontevedra, Galicia, Spain.
PLoS Comput Biol. 2023 Jul 6;19(7):e1011264. doi: 10.1371/journal.pcbi.1011264. eCollection 2023 Jul.
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.
本工作提出了一种方法来评估给定微生物转化中替代代谢途径的生物能量可行性，通过优化代谢中间产物浓度下的能量产率和驱动力来优化其能量产率和驱动力。该工具基于热力学原理和多目标优化，考虑了不同电子载体的途径变体，以及途径内的能量守恒（质子转运）反应。该方法还考虑了其他一些约束条件，其中一些是非线性的，如守恒部分的平衡。该方法涉及将最大能量产率问题转化为多目标混合整数线性优化问题，然后使用ε-约束方法对其进行求解，突出了代谢反应中产率和速率之间的权衡。该方法应用于分析厌氧发酵过程中丙酸氧化过程中发生的几种途径替代物，以及自养微生物 CO2 固定过程中发生的反向三羧酸循环途径。使用所开发的方法获得的结果与先前报道的文献相匹配，并深入了解了所研究的途径。
