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News & Views |
Making nucleic acid monomers
Amino-containing four-carbon threose nucleic acids (TNAs) have long been considered to be prebiotically irrelevant due to their difficult formation. Now, a prebiotically plausible route to 3′-amino-TNA nucleoside triphosphate has been developed, raising the possibility of 3′-amino-TNA as a non-canonical nucleic acid during the origin of life.
- Yingyu Liu
- & Yajun Wang
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Article |
Prebiotic synthesis and triphosphorylation of 3′-amino-TNA nucleosides
Nucleotides are essential to the origins of life, and their synthesis is a key challenge for prebiotic chemistry. Contrary to prior expectation, non-canonical 3′-amino-TNA nucleosides are shown to be synthesized diastereoselectively and regiospecifically under prebiotically plausible conditions. The enhanced reactivity of 3′-amino-TNAs also promotes their selective non-enzymatic triphosphorylation in water.
- Daniel Whitaker
- & Matthew W. Powner
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News & Views |
Cyanide at the origin of metabolism
The emergence of protometabolic reactions that evolved into today’s metabolic pathways is unclear. Now, evidence suggests that the chemical origin of biological carbon metabolism may have relied on the versatility of a single primitive C1 feedstock molecule — hydrogen cyanide.
- Saidul Islam
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Article |
An RNA-cleaving threose nucleic acid enzyme capable of single point mutation discrimination
Threose nucleic acid (TNA) is a potential RNA evolutionary progenitor and a nuclease-resistant synthetic genetic polymer. Now, a TNA catalyst that cleaves RNA has been identified in vitro. The TNA catalyst shows strong sequence selectivity towards a mutant RNA substrate involved in drug resistance, resulting in selective gene silencing in eukaryotic cells.
- Yueyao Wang
- , Yao Wang
- & Hanyang Yu
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News & Views |
The origin of translation
The origin and evolution of translational machinery — which produces a specific peptide from an RNA sequence — is a major unsolved puzzle in prebiotic chemistry. Now, the coupling of amino acids directed by RNA templates in the absence of a ribosome provides clues on how this protein synthesis process might have started.
- Ya Ying Zheng
- & Jia Sheng
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Editorial |
Life lessons
It is far from certain how simple chemical reactions became interconnected networks that gave rise to life on early Earth. Exploring the possible ways in which this could have occurred is an active area of research and a collection of articles in this issue consider what chemical steps may have been taken on the path towards life as we know it today.
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Harnessing chemical energy for the activation and joining of prebiotic building blocks
Life requires a constant supply of energy, but the energy sources that drove the transition from prebiotic chemistry to biochemistry on the early Earth are unknown. Now, a potentially prebiotic chemical activating reagent has been shown to enable the synthesis, in aqueous conditions and catalysed by small molecules, of peptides, peptidyl–RNAs, RNA oligomers and primordial phospholipids.
- Ziwei Liu
- , Long-Fei Wu
- & John D. Sutherland
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Article |
A plausible metal-free ancestral analogue of the Krebs cycle composed entirely of α-ketoacids
Metal-catalysed prebiotic reactions have been proposed as forerunners of modern metabolism. Now, an abiotic pathway resembling the reverse tricarboxylic acid cycle has been shown to proceed without metal catalysis. The reaction of glyoxylate and pyruvate produces a series of α-ketoacid tricarboxylic acid analogues, and provides a route to generate α-amino acids by transamination.
- R. Trent Stubbs
- , Mahipal Yadav
- & Greg Springsteen
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Article |
Discovery and evolution of RNA and XNA reverse transcriptase function and fidelity
Engineering reverse transcriptases for modified or unnatural nucleic acids is challenging, but now a versatile method has been developed that enables the discovery of efficient reverse transcriptases. The method works with a wide range of template structures, including xeno-nucleic acids and can also be used to produce high-fidelity reverse transcriptases for RNA.
- Gillian Houlihan
- , Sebastian Arangundy-Franklin
- & Philipp Holliger
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Article |
A marine viral halogenase that iodinates diverse substrates
A flavin-dependent halogenase with a remarkable preference for iodination has now been discovered. The halogenase (VirX1) was discovered using a bioinformatics-based approach and comes from a cyanophage. Structural characterization and kinetic studies show that VirX1 possesses broad substrate tolerance, making it an attractive tool for synthesis.
- Danai S. Gkotsi
- , Hannes Ludewig
- & Rebecca J. M. Goss
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Article |
Heated gas bubbles enrich, crystallize, dry, phosphorylate and encapsulate prebiotic molecules
High concentrations of prebiotic molecules and dry–wet cycles are difficult to achieve in a submerged system. Now, it has been shown that temperature gradients across gas bubbles in submerged rock pores can provide these conditions. Molecules are continuously accumulated at the warm side of bubbles at the gas–water interface, which enables or enhances many prebiotically relevant processes.
- Matthias Morasch
- , Jonathan Liu
- & Dieter Braun
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Article |
Evolution of sequence-defined highly functionalized nucleic acid polymers
A method to produce sequence-defined, diversely functionalized nucleic acid polymers that bind to proteins of biomedical interest has been developed. The method is based on a ligase-mediated, DNA-templated polymerization system and in vitro selection. The selected polymers are shown to bind their targets in a manner that is strongly dependent on specific side chains at certain polymer positions.
- Zhen Chen
- , Phillip A. Lichtor
- & David R. Liu
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Nonribosomal biosynthesis of backbone-modified peptides
Nonribosomal peptide synthetases (NRPSs) produce vital natural products but have proven recalcitrant to biosynthetic engineering. Now, a combination of yeast surface display and fluorescence-activated cell sorting (FACS) has been used to reprogram an L-Phe-incorporating module for β-Phe. The resulting module is highly selective and functions efficiently in NRPS pathways.
- David L. Niquille
- , Douglas A. Hansen
- & Donald Hilvert
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Simple peptides derived from the ribosomal core potentiate RNA polymerase ribozyme function
Lysine-rich peptides from the ribosomal core and derived homolysine decapeptides of either L-, D- or mixed chirality have now been shown to enhance RNA polymerase ribozyme activity at low magnesium concentrations, accelerate ribozyme evolution and enable templated RNA synthesis within membranous protocells.
- Shunsuke Tagami
- , James Attwater
- & Philipp Holliger
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Engineering genetic circuit interactions within and between synthetic minimal cells
Genetic circuits are important for synthetic biology, biochemistry and bioengineering. Now, the encapsulation of genetic circuits into liposomes has been shown to enable a more modular design, the selective isolation of reactions from the environment and from each other, and the hierarchical assembly of reaction products.
- Katarzyna P. Adamala
- , Daniel A. Martin-Alarcon
- & Edward S. Boyden
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Emergence of a catalytic tetrad during evolution of a highly active artificial aldolase
An artificial aldolase has been optimized using an ultrahigh-throughput microfluidic screening assay. The evolved enzyme exhibits excellent stereoselectivity and broad substrate scope. Structural studies suggest that a Lys-Tyr-Asn-Tyr catalytic tetrad, which emerged during directed evolution, is responsible for the >109 rate enhancement achieved by this catalyst.
- Richard Obexer
- , Alexei Godina
- & Donald Hilvert
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Article |
Oligoarginine peptides slow strand annealing and assist non-enzymatic RNA replication
Identifying a non-enzymatic method of replicating RNA for multiple cycles has been problematic because rapid strand reannealing outcompetes slow non-enzymatic template copying. Now, oligoarginine peptides have been shown to inhibit reannealing while still allowing short primers and activated monomers to bind to the template strand, facilitating the next round of template copying.
- Tony Z. Jia
- , Albert C. Fahrenbach
- & Jack W. Szostak
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