Competition, Cooperation, and Mutation: Improving a Synthetic Replicator by Light Irradiation

Hong, Jong‐In; Feng, Qing; Rotello, Vincent M.; Rebek, Julius

doi:10.1126/science.255.5046.848

Cited by 115 publications

(30 citation statements)

References 9 publications

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“…By comparison, trans 2c also accelerates its own formation and, unexpectedly, the formation of the cis 2a as well (S.I.). Thus, trans 2c is a cooperative (19) replicator. The trans arrangement of alkyl groups on an imidazolidinone is not expected to be advantageous for organocatalysis so trans 2c was not tested in those capacities.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Autocatalysis and organocatalysis with synthetic structures

Kamioka

Ajami

Rebek

2009

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

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The discovery of ribozymes led to the proposal of an RNA world, where a single type of molecule was supposedly capable of selfreplication and chemical catalysis. We show here that both autocatalysis and organocatalysis can be engineered into a synthetic structure. The compound is shown to selectively accelerate its own formation and catalyze either hydrogenation or nucleophilic addition to α,β-unsaturated aldehydes. The observed reactivity indicates that the components of a purported pre-RNA world conceivably include smaller organic molecules.imidazolidinone catalysis | self-replication | template effects S tudies of prebiotic chemistry raise questions concerning which functions came nearer the origin of life-genetics or metabolism (1). The discovery of the catalytic activity of ribozymes provided an answer in which both functions could be accounted for in an "RNA world" (2). Although no one doubted that RNA could carry genetic information, some 15 years lapsed before an RNA molecule was shown to self-replicate (3), and this type of catalysis has since been developed to an extraordinary level of efficiency (4). Short, self-complementary DNA strands were shown to selfreplicate in 1986 (5), and autocatalysis based on molecular recognition was found in simplified organic molecules (6) and even peptides (7). At the present time, many types of self-replicating structures are known (8). These systems function like their nucleic acid counterparts in that the self-complementary structures operate as templates for their own formation. However, unlike ribozymes, the synthetic self-replicating systems are not known to catalyze other chemical reactions. The wholly synthetic structures act as either organocatalysts or autocatalysts, but published evidence for both activities in a single molecule is limited (9). This research was undertaken to find molecules that could perform in both capacities, and we report here an imidazolidinone-based compound and its properties as a catalyst and autocatalyst. Results and DiscussionTo realize an autocatalytic/organocatalytic molecule, we made modifications in the structure of compound 1, a molecule that bears self-complementary hydrogen-bonding subunits-a diaminotriazine and cyclic imide-that allow for dimerization in noncompeting organic media (Fig. 1). The arrangement of these subunits in 1 was earlier shown to allow its action as an autocatalyst (10): It acts as a template for its own synthesis, gathering two subunits on its surface to facilitate the formation of the amide bond. The insertion of a functional group known to catalyze organic transformations into 1 was a prospect to be explored. We initially inserted a thiourea into the framework of 1 (11). Although the thiourea function is a widely used organocatalyst (12), its applications were limited in the present context: The same hydrogen bonding that accounts for the thiourea's activity requires the use of solvents that also lead to tight dimerization of the template. This effect minimizes the fraction of the monomeric compound t...

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Section: Resultsmentioning

confidence: 99%

“…Such compounds provide a starting point for a "bottom up" approach to creating molecular complexity and establishing catalytic reaction cycles (26). There is also the possibility for mutations (27) in these synthetic replicators. The ultimate aim is the generation of accessible synthetic systems that are potential precursors to the RNA world.…”

Section: Resultsmentioning

confidence: 99%

Autocatalysis and organocatalysis with synthetic structures

Kamioka

Ajami

Rebek

2009

Proc. Natl. Acad. Sci. U.S.A.

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“…These systems usually offer no choice other than to form a particular product molecule. Even in those cases where one template can direct the synthesis of multiple products (13,31,35), the products do not ''breed true'' such that each product species only gives rise to additional copies of itself. Furthermore, product formation typically involves only a single joining reaction.…”

mentioning

confidence: 99%

A self-replicating ligase ribozyme

Paul

Joyce²

2002

Proc. Natl. Acad. Sci. U.S.A.

224

161

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A self-replicating molecule directs the covalent assembly of component molecules to form a product that is of identical composition to the parent. When the newly formed product also is able to direct the assembly of product molecules, the self-replicating system can be termed autocatalytic. A self-replicating system was developed based on a ribozyme that catalyzes the assembly of additional copies of itself through an RNA-catalyzed RNA ligation reaction. The R3C ligase ribozyme was redesigned so that it would ligate two substrates to generate an exact copy of itself, which then would behave in a similar manner. This self-replicating system depends on the catalytic nature of the RNA for the generation of copies. A linear dependence was observed between the initial rate of formation of new copies and the starting concentration of ribozyme, consistent with exponential growth. The autocatalytic rate constant was 0.011 min ؊1 , whereas the initial rate of reaction in the absence of pre-existing ribozyme was only 3.3 ؋ 10 ؊11 M⅐min ؊1 . Exponential growth was limited, however, because newly formed ribozyme molecules had greater difficulty forming a productive complex with the two substrates. Further optimization of the system may lead to the sustained exponential growth of ribozymes that undergo self-replication. In living systems, replicative processes transfer genetic information from template nucleic acid molecules to newly synthesized, complementary products. Several nonenzymatic templatedependent ligation systems have been devised to study the role of a template in binding and positioning complementary substrates for covalent bond formation (1-5). These have included simple self-replicating systems of the form A ϩ B 3 T, where A and B are substrates that bind to a complementary template, T, and become joined to form a product molecule that is identical to the template (6-9). The unique aspect of self-replicating systems is that the reaction product has the potential to direct additional reactions. The system is termed autocatalytic when the product is an efficient template, and each covalent bond that is formed generates additional template molecules that can direct further joining reactions. The realization of autocatalytic behavior in a self-replicating system implies that sustained exponential growth may be possible.The self-replicating systems that have been studied to date use template molecules composed of nucleic acids (6, 7, 10), peptides (11-14), or small organic compounds (15-17). The nucleic acid-based systems are the most straightforward and rely on simple Watson-Crick pairing interactions between a short oligonucleotide template and two complementary oligonucleotide substrates (6, 7, 10). The substrates are bound at adjacent positions along the template and are joined through a reaction involving chemical groups at their opposed ends. Peptide-based self-replicating systems are similar, except that the components are oligopeptides that have the capacity to form ␣-helices. The template is the hydrophob...

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“…The systems are programmable in the sense that the choice of primer DNA sequences, which are buffered at high concentration and act as substrates for the polymerization reactions, strongly in uence the type of system that can emerge. Very recently, symbiotic in vitro ecosystems on the basis of self-replicating peptides have also been created [13], and similar work is in progress on enzyme-free self-replication of nucleic acids [26] and organic molecules [11].…”

Section: In Vitro Molecular Ecosystemsmentioning

confidence: 98%

Evolving Reaction-Diffusion Ecosystems with Self-Assembling Structures in Thin Films

Breyer¹,

Ackermann²,

McCaskill³

1998

Artificial Life

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Recently, new types of coupled isothermal polynucleotide amplification reactions for the investigation of in vitro evolution have been established that are based on the multi-enzyme 3SR reaction. Microstructured thin-film open bioreactors have been constructed in our laboratory to run these reactions spatially resolved in flow experiments. Artificial DNA/RNA chemistries close to the in vitro biochemistry of these systems have been developed, which we have studied in computer simulations in configurable hardware (NGEN). These artificial chemistries are described on the level of individual polynucleotide molecules, each with a defined sequence, and their complexes. The key feature of spatial pattern formation provides a weak stabilization of cooperative catalytic properties of the evolving molecules. Of great interest is the step to include extended self-assembly processes of flexible structures-allowing the additional stabilization of cooperation through semipermeable, flexible, self-organizing membrane boundaries. We show how programmable matter simulations of experimentally relevant molecular in vitro evolution can be extended to include the influence of self-assembling flexible membranes.

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Competition, Cooperation, and Mutation: Improving a Synthetic Replicator by Light Irradiation

Cited by 115 publications

References 9 publications

Autocatalysis and organocatalysis with synthetic structures

Autocatalysis and organocatalysis with synthetic structures

A self-replicating ligase ribozyme

Evolving Reaction-Diffusion Ecosystems with Self-Assembling Structures in Thin Films

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