Department of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands.
Nat Commun. 2024 Sep 12;15(1):7976. doi: 10.1038/s41467-024-52085-z.
Cellular homeostasis depends on the supply of metabolic energy in the form of ATP and electrochemical ion gradients. The construction of synthetic cells requires a constant supply of energy to drive membrane transport and metabolism. Here, we provide synthetic cells with long-lasting metabolic energy in the form of an electrochemical proton gradient. Leveraging the L-malate decarboxylation pathway we generate a stable proton gradient and electrical potential in lipid vesicles by electrogenic L-malate/L-lactate exchange coupled to L-malate decarboxylation. By co-reconstitution with the transporters GltP and LacY, the synthetic cells maintain accumulation of L-glutamate and lactose over periods of hours, mimicking nutrient feeding in living cells. We couple the accumulation of lactose to a metabolic network for the generation of intermediates of the glycolytic and pentose phosphate pathways. This study underscores the potential of harnessing a proton motive force via a simple metabolic network, paving the way for the development of more complex synthetic systems.
细胞内环境的稳定依赖于以 ATP 和电化学离子梯度形式供应的代谢能量。合成细胞的构建需要持续的能量供应来驱动膜运输和代谢。在这里，我们以电化学质子梯度的形式为合成细胞提供持久的代谢能量。利用 L-苹果酸脱羧途径，我们通过电致 L-苹果酸/L-乳酸交换与 L-苹果酸脱羧偶联，在脂质体中产生稳定的质子梯度和电势能。通过与转运蛋白 GltP 和 LacY 共重建，合成细胞可以在数小时内维持 L-谷氨酸和乳糖的积累，模拟活细胞中的营养物质摄取。我们将乳糖的积累与糖酵解和磷酸戊糖途径中间产物的代谢网络偶联起来。这项研究强调了通过简单的代谢网络利用质子动力势的潜力，为开发更复杂的合成系统铺平了道路。
