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Toward the assembly of a minimal divisome

机译:迈向最小的组装

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The construction of an irreducible minimal cell having all essential attributes of a living system is one of the biggest challenges facing synthetic biology. One ubiquitous task accomplished by any living systems is the division of the cell envelope.Hence, the assembly of an elementary, albeit sufficient, molecular machinery that supports compartment division, is a crucial step towards the realization of self-reproducing artificial cells. Looking backward to the molecular nature of possible ancestral, supposedly more rudimentary, cell division systems may help to identify a minimal divisome. In light of a possible evolutionary pathway of division mechanisms from simple lipid vesicles toward modern life, we define two approaches for recapitulating division in primitive cells: the membrane deforming protein route and the lipid biosynthesis route. Having identified possible proteins and working mechanisms participating in membrane shape alteration, we then discuss how they could be integrated into the construction framework of a programmable minimal cell relying on gene expression inside liposomes. The protein synthesis using recombinant elements (PURE) system, a reconstituted minimal gene expression system, is conceivably the most versatilesynthesis platform. As a first step towards the de novo synthesis of a divisome, we showed that the N-BAR domain protein produced from its gene could assemble onto the outer surface of liposomes and sculpt the membrane into tubular structures. We finally discuss the remaining challenges for building up a self-reproducing minimal cell, in particularthe coupling of the division machinery with volume expansion and genome replication.
机译:具有生命系统所有基本属性的不可还原的最小细胞的构建是合成生物学面临的最大挑战之一。任何生物系统都完成的一项无处不在的任务是细胞包膜的分裂。因此,组装一个虽然足够的基本分子机器来支持隔室分裂,却是实现自我复制人造细胞的关键一步。回顾可能祖传的分子性质(据说更原始),细胞分裂系统可能有助于鉴定最小的杂种。鉴于从简单脂质囊泡到现代生活的分裂机制的可能进化途径,我们定义了两种概括原始细胞分裂的方法:膜变形蛋白途径和脂质生物合成途径。在确定可能的蛋白质和参与膜形状改变的工作机制后,我们将讨论如何将它们整合到依赖脂质体内基因表达的可编程最小细胞的构建框架中。使用重组元件(PURE)系统(一种重构的最小基因表达系统)进行的蛋白质合成可能是功能最广泛的合成平台。作为从头合成从头开始的第一步,我们显示了由其基因产生的N-BAR结构域蛋白可以装配到脂质体的外表面,并将膜雕刻成管状结构。最后,我们讨论了构建自我复制的最小细胞所面临的挑战,特别是分裂机制与体积扩增和基因组复制的耦合。

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