For life to emerge, confinement of catalytic reactions within protocellular environments has been proposed as a decisive aspect to regulate chemical activity in space. 1,2 Today, cells and organisms adapt to signals [3][4][5][6][7] by processing them through reaction networks that ultimately provide downstream functional responses and structural morphogenesis. 8,9 Re-enacting such signal processing in de-novo designed protocells is a profound challenge, but of high importance for understanding the design of adaptive systems with life-like traits. We report on engineered all-DNA protocells 10 harboring an artificial metalloenzyme 11 whose olefin metathesis activity leads to downstream morphogenetic protocellular responses with varying levels of complexity. The artificial metalloenzyme catalyzes the uncaging of a pro-fluorescent signal molecule, that generates a self-reporting fluorescent metabolite designed to weaken DNA duplex interactions. This leads to pronounced growth, intra-particular functional adaptation in the presence of a fluorescent DNA mechanosensor, 12 or inter-particle protocell fusion. Such processes mimic chemically transduced processes found in cell adaptation and cell-to-cell adhesion. Our concept showcases new opportunities to study lifelike behavior via abiotic bioorthogonal chemical and mechanical transformations in synthetic protocells. Furthermore, it reveals a strategy for inducing complex behavior in adaptive-and communicating softmatter microsystems, and illustrates how dynamic properties can be upregulated and sustained in microcompartmentalized media.Living cells are highly inspiring for their unique ability to perform complex tasks, such as division, differentiation and tissue formation via internal signal processing and intercellular communication. 6,13 In cells, a diversity of different signals are processed in a crowded environment using reaction networks, that may even be organized spatially in liquid/liquid phase-segregated membraneless organelles. [14][15][16] Protocell models resulting from the self-assembly of amphiphiles, such as phospholipid liposomes, have been used to investigate prebiotic compartmentalization and primitive processes, such as catalysis, metabolism, and replication. [17][18][19][20] These however, seldom recapitulate some of the critical features that are essential to cellular function: macromolecular crowding and phase-segregation. 21 To this end, (bio)polymer coacervates have been suggested as model systems, and recent studies have reported gene expression, 15 ribonucleic acid catalysis 22 and multienzyme iterative processing in multicomponent microdroplets. 23,24 Some of the most complex mimics may include DNA-containing protocells that can exchange DNA as information and may allow for simple communication. 25,26 However, it is of critical importance to develop strategies able to convert signals from diverse origin to allow for intra-or inter-protocell downstream processes such as functional adaptation, communication and simple morphogenesis which may, i...

Bioorthogonal uncaging reactions offer versatile tools in chemical biology. In recent years, reactions have been developed to proceed efficiently under physiological conditions. We present herein an uncaging reaction that results from ring-closing metathesis (RCM). A caged molecule, tethered to a diolefinic substrate, is released via spontaneous 1,4-elimination following RCM. Using this strategy, which we term “close-to-release”, we show that drugs and fluorescent probes are uncaged with fast rates, including in the presence of mammalian cells or in the periplasm of Escherichia coli. We envision that this tool may find applications in chemical biology, bioengineering and medicine.

Olefin metathesis is one of the most powerful C–C double-bond-forming reactions. Metathesis reactions have had a tremendous impact in organic synthesis, enabling a variety of applications in polymer chemistry, drug discovery and chemical biology. Although challenging, the possibility to perform aqueous metatheses has become an attractive alternative, not only because water is a more sustainable medium, but also to exploit biocompatible conditions. This review focuses on the progress made in aqueous olefin metatheses and their applications in chemical biology.

The streptavidin scaffold was expanded with well-structured naturally occurring motifs. These chimeric scaffolds were tested as host for biotinylated catalysts as artificial metalloenzymes (ArM) for asymmetric transfer hydrogenation, ring closing metathesis and

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