Bioinformatics Program, Boston University, Boston, MA, USA.
Department of Chemistry, Boston University, Boston, MA, USA.
Nat Ecol Evol. 2019 Dec;3(12):1715-1724. doi: 10.1038/s41559-019-1018-8. Epub 2019 Nov 11.
It has been suggested that a deep memory of early life is hidden in the architecture of metabolic networks, whose reactions could have been catalyzed by small molecules or minerals before genetically encoded enzymes. A major challenge in unravelling these early steps is assessing the plausibility of a connected, thermodynamically consistent proto-metabolism under different geochemical conditions, which are still surrounded by high uncertainty. Here we combine network-based algorithms with physico-chemical constraints on chemical reaction networks to systematically show how different combinations of parameters (temperature, pH, redox potential and availability of molecular precursors) could have affected the evolution of a proto-metabolism. Our analysis of possible trajectories indicates that a subset of boundary conditions converges to an organo-sulfur-based proto-metabolic network fuelled by a thioester- and redox-driven variant of the reductive tricarboxylic acid cycle that is capable of producing lipids and keto acids. Surprisingly, environmental sources of fixed nitrogen and low-potential electron donors are not necessary for the earliest phases of biochemical evolution. We use one of these networks to build a steady-state dynamical metabolic model of a protocell, and find that different combinations of carbon sources and electron donors can support the continuous production of a minimal ancient 'biomass' composed of putative early biopolymers and fatty acids.
有人提出，早期生活的深刻记忆隐藏在代谢网络的结构中，在基因编码酶出现之前，这些反应可能是由小分子或矿物质催化的。在揭示这些早期步骤的过程中，一个主要的挑战是评估在不同地球化学条件下，一个连接的、热力学一致的原始新陈代谢的可能性，而这些条件仍然存在高度的不确定性。在这里，我们将基于网络的算法与化学反应网络的物理化学约束相结合，系统地展示了不同参数组合（温度、pH 值、氧化还原电位和分子前体的可用性）如何影响原始新陈代谢的进化。我们对可能轨迹的分析表明，一组边界条件收敛到一个基于有机硫的原始代谢网络，该网络由硫酯和氧化还原驱动的还原三羧酸循环的变体提供燃料，能够产生脂质和酮酸。令人惊讶的是，固定氮和低电位电子供体的环境来源对于生化进化的最早阶段并不是必需的。我们使用其中一个网络构建了一个原细胞的稳态动力代谢模型，并发现不同的碳源和电子供体组合可以支持由假定的早期生物聚合物和脂肪酸组成的最小古代“生物量”的连续产生。
