Templated Self‐Replication in Biomimetic Systems

Abstract

nanostructures and nanopatterns. [13][14][15] The specificity of the molecular recognitions between replicative units is concomitant with the encoding and transmission of information, with the degree of specificity determining the fidelty and capacity of information transfer against competing background interactions in noisy "chemical" environments. [16] However, the ability to replicate in this manner does not imply the ability to transmit additional heritable information-simple replicators can only replicate information related to recognition and template directed autocatalysis as this information is intrinsically linked to phenotype. In contrast to most artificial autocatalytic replicators, living systems (including viruses) store the key instructions for replication on an inheritable genetic system rather than in the native structures of the individual sub-components. This decoupling of phenotype and genotype enables heredity and open-ended evolution, the possibility of an indefinite increase in complexity, as evolutionary innovations aquired by natural selection are anchored in the genotype only. [17,18] The most prominent self-replicating molecules are nucleic acids, which form the fundamental basis for information storage and propagation in biological systems. The ability of polynucleic acids to store information is self-evident, and based upon the ability to form cognate Watson-Crick base pair interactions. Nucleic acid systems may have also formed the first genetic replicators in biology. The RNA world hypothesis postulates a stage in the origin of life in which RNA proliferated before the emergence of DNA and proteins. To do this, RNA must be able to carry out several key roles: information storage, catalysis, and (self-) replication. Multiple examples of catalytic RNAs (ribozymes) are known both from nature and in vitro selection experiments, [19][20][21][22] but there is no fossil evidence of an RNA capable of (self-)replication without the involvement of proteins.While minimal nucleic acid-only systems with replicationlike properties have been identified by directed evolution and engineering, limitations such as low activity, lack of generality, and poor information capacity limit their usefulness in bottomup synthetic biology, except in origin of life research. For the creation of more complex biological in vitro systems, RNA or DNA replication mechanisms involving more powerful protein enzymes are likely to be necessary. Even so, the achievement of self-sustained in vitro self-replication inspired by the central dogma of molecular biology is currently hampered by the requirement to encode and efficiently express the enormous A key characteristic of living systems is the storage and replication of information, and as such the development of self-replicating systems capable of heredity is of great importance to the fields of synthetic biology and origin of life research. In this review, the design and implementation of self-replicating systems in the context of bottom-up synthetic biology is discusse...

The Long Road to a Synthetic Self-Replicating Central Dogma

“…Over the course of the past two decades, the PURE system has been adopted as a representative model for the development of a minimal protein-based system capable of self-replication and Darwinian evolution under controlled conditions. When employed as a self-encoded enzyme-catalyzed replicator, PURE relies on an external supply of protein synthesis machinery; in this format, it resembles viruses rather than self-sustained cells in that it requires more external information for its replication than it can encode . Even though it presents a relatively minimal composition, PURE shows an intrinsic complexity of interaction between its building blocks, which renders the development of a self-replicating in vitro system challenging.…”

“…When employed as a self-encoded enzyme-catalyzed replicator, PURE relies on an external supply of protein synthesis machinery; in this format, it resembles viruses rather than self-sustained cells in that it requires more external information for its replication than it can encode. 11 Even though it presents a relatively minimal composition, PURE shows an intrinsic complexity of interaction between its building blocks, which renders the development of a self-replicating in vitro system challenging. Existing versions of PURE have not proven to be capable of fully regenerating their own macromolecular components while recycling and degrading metabolic byproducts, underlining the fact that, in its current format, PURE cannot remake PURE.…”

Deep sequencing of non-enzymatic RNA primer extension

“…This versatility allows for the study of any standard RNA primer extension experiment on any template, and the use of substrates in any combination so long as they are compatible with RT ( 53 ). We anticipate that NERPE-Seq could easily be modified for DNA-based non-enzymatic reactions ( 54 ), as well as biological or putative ribozyme-catalyzed primer extension ( 55 ).…”

Phase‐Separated Droplets Can Direct the Kinetics of Chemical Reactions Including Polymerization, Self‐Replication and Oscillating Networks

“…To replicate the sequence information stored in prebiotic biopolymers, self-replication is thought to have preceded more complex enzyme-based replication. [54,55] Self-replicating DNAs, [56,57] peptides, [58,59] ribozymes [60][61][62] and synthetic molecules [63,64] have been developed, which replicate themselves by coordination of two building blocks to a template, which increases the effective molarity of the building blocks and facilitates their ligation, forming a copy of the template molecule (Figure 3a). A general problem in most of these systems, however, is product inhibition: dissociation of the formed template duplex is so slow that it prevents the product template from catalyzing a new round of replication.…”