Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstr. 1, Magdeburg, Germany.
Nat Commun. 2023 Aug 3;14(1):4660. doi: 10.1038/s41467-023-40297-8.
The ubiquitous coexistence of the redox cofactors NADH and NADPH is widely considered to facilitate an efficient operation of cellular redox metabolism. However, it remains unclear what shapes the NAD(P)H specificity of specific redox reactions. Here, we present a computational framework to analyze the effect of redox cofactor swaps on the maximal thermodynamic potential of a metabolic network and use it to investigate key aspects of redox cofactor redundancy in Escherichia coli. As one major result, our analysis suggests that evolved NAD(P)H specificities are largely shaped by metabolic network structure and associated thermodynamic constraints enabling thermodynamic driving forces that are close or even identical to the theoretical optimum and significantly higher compared to random specificities. Furthermore, while redundancy of NAD(P)H is clearly beneficial for thermodynamic driving forces, a third redox cofactor would require a low standard redox potential to be advantageous. Our approach also predicts trends of redox-cofactor concentration ratios and could facilitate the design of optimal redox cofactor specificities.
氧化还原辅因子 NADH 和 NADPH 的普遍共存被广泛认为有助于细胞氧化还原代谢的有效运作。然而，目前尚不清楚是什么塑造了特定氧化还原反应的 NAD(P)H 特异性。在这里，我们提出了一个计算框架来分析氧化还原辅因子交换对代谢网络最大热力学势的影响，并利用它来研究大肠杆菌氧化还原辅因子冗余的关键方面。作为一个主要结果，我们的分析表明，进化的 NAD(P)H 特异性在很大程度上受到代谢网络结构和相关热力学限制的影响，这些限制使热力学驱动力接近甚至等同于理论最佳值，并且明显高于随机特异性。此外，虽然 NAD(P)H 的冗余对于热力学驱动力显然是有利的，但第三种氧化还原辅因子需要低标准氧化还原电位才能具有优势。我们的方法还可以预测氧化还原辅因子浓度比的趋势，并有助于设计最佳氧化还原辅因子特异性。
