具有自扩增质子产生的工程人工线粒体在人工细胞中的自主能量供应和代谢耦合。

IF 16.9 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Fangqin Fu,Xuemei Hu,Shijia Tao,Yu Gao,Daniel Crespy,Katharina Landfester,Xiangzhao Mao,Shuai Jiang
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引用次数: 0

摘要

在人造细胞中,持续自主的能量供应是维持生命生化过程所必需的。尽管在模拟线粒体能量转换的人造细胞器工程上已经付出了相当大的努力,但产生一个强大的跨膜质子梯度仍然是一个主要挑战,这是驱动高效ATP产生的必要条件。在这里,我们提出了一个线粒体模拟ATP纳米发生器,通过定量共区隔葡萄糖氧化酶和过氧化氢酶在二氧化硅纳米胶囊内构建。酶在形成核壳纳米胶囊的过程中被封装在原位,从而实现精确的装载,有效的保护,并创建一个促进催化协同作用的受限纳米级反应室。在这个微环境中,过氧化氢酶迅速分解H2O2生成O2,而O2又被葡萄糖氧化酶利用——从而建立了一个自我强化的酶级联,放大了质子的产生。在负载酶的纳米胶囊上包裹ATP酶整合脂质体双层膜以构建人工线粒体后,所产生的质子梯度穿过膜有效地驱动ATP合成酶旋转,从而实现高产ATP的生产。当整合到巨型单层囊泡(GUVs)作为合成细胞模型时,该系统支持自主烟酰胺腺嘌呤二核苷酸(NADH)生物合成和葡萄糖氧化磷酸化,模拟活线粒体的关键代谢特征。这项工作为工程能源自主人工生命系统建立了一个有效和通用的平台,推动了自下而上合成生物学的发展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Engineering Artificial Mitochondria with Self-Amplifying Proton Generation for Autonomous Energy Supply and Metabolic Coupling in Artificial Cells.
A continuous and autonomous energy supply is essential for sustaining life-like biochemical processes in artificial cells. Although considerable efforts have been devoted to engineering artificial organelles that emulate mitochondrial energy conversion, the generation of a robust transmembrane proton gradient-essential for driving efficient ATP production-remains a major challenge. Here, we present a mitochondria-mimicking ATP nano-generator constructed through quantitative co-compartmentalization of glucose oxidase and catalase within silica nanocapsules. Enzymes are encapsulated in situ during the formation of core-shell nanocapsules, enabling precise loading, effective protection, and creation of a confined nanoscale reaction chamber that fosters catalytic synergy. Within this microenvironment, catalase rapidly decomposes H2O2 to generate O2, which is in turn utilized by glucose oxidase-thus establishing a self-reinforcing enzymatic cascade that amplifies proton production. After coating the enzyme-loaded nanocapsules with an ATPase-integrated liposome bilayer to construct the artificial mitochondrion, the resulting proton gradient across the membrane efficiently drives ATP synthase rotation, enabling high-yield ATP production. When integrated into giant unilamellar vesicles (GUVs) as synthetic cell models, this system supports autonomous nicotinamide adenine dinucleotide (NADH) biosynthesis and glucose-powered oxidative phosphorylation, mimicking key metabolic features of living mitochondria. This work establishes an effective and versatile platform for engineering energy-autonomous artificial living systems, advancing the state of the art of bottom-up synthetic biology.
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来源期刊
CiteScore
26.60
自引率
6.60%
发文量
3549
审稿时长
1.5 months
期刊介绍: Angewandte Chemie, a journal of the German Chemical Society (GDCh), maintains a leading position among scholarly journals in general chemistry with an impressive Impact Factor of 16.6 (2022 Journal Citation Reports, Clarivate, 2023). Published weekly in a reader-friendly format, it features new articles almost every day. Established in 1887, Angewandte Chemie is a prominent chemistry journal, offering a dynamic blend of Review-type articles, Highlights, Communications, and Research Articles on a weekly basis, making it unique in the field.
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