Building Synthetic Cells─From the Technology Infrastructure to Cellular Entities

ACS Synthetic Biology, Journal Year: 2024, Volume and Issue: 13(4), P. 974 - 997

Published: March 26, 2024

The de novo construction of a living organism is compelling vision. Despite the astonishing technologies developed to modify cells, building functioning cell "from scratch" has yet be accomplished. pursuit this goal alone has─and will─yield scientific insights affecting fields as diverse biology, biotechnology, medicine, and astrobiology. Multiple approaches have aimed create biochemical systems manifesting common characteristics life, such compartmentalization, metabolism, replication derived features, evolution, responsiveness stimuli, directed movement. Significant achievements in synthesizing each these criteria been made, individually limited combinations. Here, we review efforts, distinguish different approaches, highlight bottlenecks current research. We look ahead at what work remains accomplished propose "roadmap" with key milestones achieve vision cells from molecular parts.

Language: Английский

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A roadmap toward the synthesis of life

Chem, Journal Year: 2025, Volume and Issue: unknown, P. 102399 - 102399

Published: Feb. 1, 2025

Language: Английский

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Dissipative Systems Driven by the Decarboxylation of Activated Carboxylic Acids

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(7), P. 889 - 899

Published: March 14, 2023

ConspectusThe achievement of artificial systems capable being maintained in out-of-equilibrium states featuring functional properties is a main goal current chemical research. Absorption electromagnetic radiation or consumption species (a "chemical fuel") are the two strategies typically employed to reach such states, which have persist as long one above stimuli present. For this reason often referred "dissipative systems". In simplest scheme, dissipative system initially found resting, equilibrium state. The addition fuel causes shift an When exhausted, reverts initial, Thus, from mechanistic standpoint, turns out be catalyst for consumption. It has noted that, although very simple, scheme implies chance temporally control system. principle, modulating nature and/or amount added, can full time spent by state.In 2016, we that 2-cyano-2-phenylpropanoic acid (1a), whose decarboxylation proceeds smoothly under mild basic conditions, could used drive back and forth motion catenane-based molecular switch. donates proton catenane passes neutral state A transient protonated B. Decarboxylation resulting carboxylate (1acb), generates carbanion, which, strong base, retakes consequently, returns initial A. larger added fuel, longer transient, Since then, 1a other activated carboxylic acids (ACAs) been operation large number based on acid-base reaction, machines host-guest systems, catalysts smart materials, so on. This Account illustrates with purpose show wide applicability ACAs fuels. generality due simplicity idea underlying principle ACAs, always translates into simple experimental requirements.

Language: Английский

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Artificial cell synthesis using biocatalytic polymerization-induced self-assembly

Nature Chemistry, Journal Year: 2023, Volume and Issue: 16(4), P. 564 - 574

Published: Dec. 4, 2023

Abstract Artificial cells are biomimetic microstructures that mimic functions of natural cells, can be applied as building blocks for molecular systems engineering, and host synthetic biology pathways. Here we report enzymatically synthesized polymer-based artificial with the ability to express proteins. were using biocatalytic atom transfer radical polymerization-induced self-assembly, in which myoglobin synthesizes amphiphilic block co-polymers self-assemble into structures such micelles, worm-like polymersomes giant unilamellar vesicles (GUVs). The GUVs encapsulate cargo during polymerization, including enzymes, nanoparticles, microparticles, plasmids cell lysate. resulting act microreactors enzymatic reactions osteoblast-inspired biomineralization. Moreover, they proteins a fluorescent protein actin when fed amino acids. Actin polymerizes alters cells’ internal structure by creating compartments. Thus, self-assembly-derived bacteria composed microscopic reaction compartment contains genetic information expression upon induction.

Language: Английский

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The protometabolic nature of prebiotic chemistry

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(21), P. 7359 - 7388

Published: Jan. 1, 2023

This tutorial review revises the main synthetic pathways of prebiotic chemistry, suggesting how they could be wired through common intermediates and catalytic cycles, as well boundary conditions under which would become protometabolic.

Language: Английский

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Constructing artificial gap junctions to mediate intercellular signal and mass transport

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(9), P. 1418 - 1426

Published: April 24, 2024

Language: Английский

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Template-based copying in chemically fuelled dynamic combinatorial libraries

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(8), P. 1240 - 1249

Published: July 16, 2024

Abstract One of science’s greatest challenges is determining how life can spontaneously emerge from a mixture molecules. A complicating factor that and its molecules are inherently unstable—RNA proteins prone to hydrolysis denaturation. For the de novo synthesis or better understand emergence at origin, selection mechanisms needed for unstable Here we present chemically fuelled dynamic combinatorial library model RNA oligomerization deoligomerization shine new light on purification under kinetic control. In experiments, oligomers only be sustained by continuous production. Hybridization powerful tool selecting molecules, offering feedback rates. Moreover, find templation used purify libraries oligomers. addition, template-assisted formation within coacervate-based protocells changes compartment’s physical properties, such as their ability fuse. Such reciprocal coupling between oligomer production properties key step towards synthetic life.

Language: Английский

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Photoswitchable Imines Drive Dynamic Covalent Systems to Nonequilibrium Steady States

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(30), P. 20720 - 20727

Published: July 18, 2024

Coupling a photochemical reaction to thermal exchange process can drive the latter nonequilibrium steady state (NESS) under photoirradiation. Typically, systems use separate motifs for photoresponse and equilibrium-related processes. Here, we show that photoswitchable imines fulfill both roles simultaneously, autonomously driving dynamic covalent system into NESS continuous light irradiation. We demonstrate this using transimination reactions, where

Language: Английский

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Open-endedness in synthetic biology: A route to continual innovation for biological design

Science Advances, Journal Year: 2024, Volume and Issue: 10(3)

Published: Jan. 19, 2024

Design in synthetic biology is typically goal oriented, aiming to repurpose or optimize existing biological functions, augmenting with new-to-nature capabilities, creating life-like systems from scratch. While the field has seen many advances, bottlenecks complexity of built are emerging and designs that function lab often fail when used real-world contexts. Here, we propose an open-ended approach design, novelty designed being at least as important how well it fulfils its goal. Rather than solely focusing on optimization toward a single best designing mind may allow us move beyond diminishing returns see performance for most engineered biology. Research artificial life community demonstrated embracing can automatically generate innovative unexpected solutions challenging problems local optima. Synthetic offers ideal playground explore more creative approaches design.

Language: Английский

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Kinetically Controlled and Nonequilibrium Assembly of Block Copolymers in Solution

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(28), P. 18781 - 18796

Published: July 5, 2024

Covalent polymers are versatile macromolecules that have found widespread use in society. Contemporary methods of polymerization made it possible to construct sequence polymers, including block copolymers, with high precision. Such copolymers assemble solution when the blocks differing solubilities. This produces nano- and microparticles various shapes sizes. While is straightforward draw an analogy between such amphiphilic phospholipids, these two classes molecules show quite different assembly characteristics. In particular, often under kinetic control, thus producing nonequilibrium structures. leads a rich variety behaviors being observed copolymer assembly, as pathway dependence (e.g., thermal history), nonergodicity responsiveness. The dynamics polymer assemblies can be readily controlled using changes environmental conditions and/or integrating functional groups situated on external chemical reactions. perspective highlights control both pervasive useful attribute mechanics assembly. Recent examples highlighted order toggling static dynamic behavior used generate, manipulate dismantle states. New kinetics will provide endless unanticipated applications materials science, biomimicry medicine.

Language: Английский

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