A route to enantiopure RNA precursors from nearly racemic starting materials

Hein, Jason E.; Tse, Eric; Blackmond, Donna G.

doi:10.1038/nchem.1108

Cited by 105 publications

(98 citation statements)

References 25 publications

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“…the exclusion of 13f) and expanded the amino acid repertoire to provide further selective advantages. 4,34 Finally, and importantly, it is of particular note that 2-aminothiazole (7) does not inhibit the formation of pentose aminooxazoline (1) by Mannich-type reactivity, 14,25,35 or the formation of the canonical α-amino acids through participation in Strecker-type reactivity. Accordingly, it is remarkable that 2-aminothiazole (7) can react with ribonucleotide and amino acid aldehyde precursors and facilitate their purification and accumulation from prebiotic mixtures.…”

Section: Discussionmentioning

confidence: 99%

Prebiotic selection and assembly of proteinogenic amino acids and natural nucleotides from complex mixtures

2017

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UK 2A central problem for prebiotic synthesis of the biological amino acids and nucleotides is avoiding the concomitant synthesis of undesired or irrelevant byproducts. Additionally, multistep pathways require mechanisms that enable the sequential addition of reactants and purification of intermediates that are consistent with reasonable geochemical scenarios. Here, we show that 2-aminothiazole reacts selectively with two-and three-carbon sugars (glycolaldehyde and glyceraldehyde, respectively), which results in their accumulation and purification as stable crystalline aminals. This permits ribonucleotide synthesis, even from complex sugar mixtures. Remarkably, aminal formation also overcomes the thermodynamically favoured isomerisation of glyceraldehyde to dihydroxyacetone because only the aminal of glyceraldehyde separates from the equilibrating mixture. Finally, we show that aminal formation provides a novel pathway to amino acids that avoids synthesis of the non-proteinogenic α,α-disubstituted analogues. The common physicochemical mechanism that controls proteinogenic amino acid and ribonucleotide assembly from prebiotic mixtures suggests these essential classes of metabolite had a unified chemical origin. 3The conservation of the genetic code, amino acids, and nucleotides in biology suggests a single origin of life on Earth. [1][2][3][4][5][6][7][8][9][10][11][12][13] Proteins are built from a highly restricted set of about 20 amino acids according to a universal triplet code of four ribonucleotides. Therefore, it is essential to learn how this specific small constellation of molecules became irrevocably linked at the advent of life. In contrast to the narrow distribution of universal metabolites observed in biology, typical prebiotic reactions are notorious for their complex product distributions. Accordingly, it has been recognised that "the chief obstacle to understanding the origin of RNA-based life is identifying a plausible mechanism for overcoming the clutter wrought by prebiotic chemistry". [4][5][6][7] For example, the most-efficient and specific proposed prebiotic pathway to the pyrimidine ribonucleotides requires synthesis of the key intermediate pentose aminooxazoline (1) (Fig. 1a). [2][3][4][5][6][22][23][24] However, the plausibility of this proposed prebiotic synthesis of pentose aminooxazoline (1) has been questioned because it is contingent upon the strictly controlled sequential delivery of pure glycolaldehyde (2a) to cyanamide (3) to yield 2-aminooxazole (4), followed by pure glyceraldehyde (2b) to 2-aminooxazole (4) to yield the desired product (Fig. 1a). This is a serious problem because both of these reactions lack the intrinsic selectivity required to exclusively yield their respective products (2-aminooxazole (4) and pentose aminooxazoline (1)) from mixtures of glycolaldehyde (2a) and glyceraldehyde (2b). The problem becomes increasingly worse in the presence of other sugars. Without a separate and sequential delivery of glycolaldehyde (2a) and glyceraldehyde (2b), a complex mixture...

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Section: Discussionmentioning

confidence: 99%

Prebiotic selection and assembly of proteinogenic amino acids and natural nucleotides from complex mixtures

2017

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“…Enantiomeric enrichment from an initial imbalance can occur through physical [133,134] or chemical [135] amplification processes. Predominantly L-handed amino-oxazolines-precursors to RNA-are formed from the reaction of amino-oxazole with glyceraldehyde at a 1% excess of the L-enantiomer in the presence of chiral amino acids [136]. After the emergence of L-RNA, L-amino acids could then have determined the handedness of the D-sugars we see in life today [137].…”

Section: Selectionmentioning

confidence: 99%

A Chemical Engineering Perspective on the Origins of Life

Grover

Hsieh

et al. 2015

Processes

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Atoms and molecules assemble into materials, with the material structure determining the properties and ultimate function. Human-made materials and systems have achieved great complexity, such as the integrated circuit and the modern airplane. However, they still do not rival the adaptivity and robustness of biological systems. Understanding the reaction and assembly of molecules on the early Earth is a scientific grand challenge, and also can elucidate the design principles underlying biological materials and systems. This research requires understanding of chemical reactions, thermodynamics, fluid mechanics, heat and mass transfer, optimization, and control. Thus, the discipline of chemical engineering can play a central role in advancing the field. In this paper, an overview of research in the origins field is given, with particular emphasis on the origin of biopolymers and the role of chemical engineering phenomena. A case study is presented to highlight the importance of the environment and its coupling to the chemistry.

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“…In the very next step on the pathway to nucleotide synthesis, 2AO reacts with the sugar glyceraldehyde to form the key intermediate ribose aminooxazoline (RAO). Remarkably, RAO crystallizes out of solution ( Figure 5), leaving behind left over starting materials as well as all of the other products are made 12,13 . You can imagine this occurring on a geological scale, and building up a large reservoir of this crystalline intermediate.…”

Section: Systems Chemistry and The Synthesis Of 2-aminooxazole Glymentioning

confidence: 99%

The Origin of Life on Earth and the Design of Alternative Life Forms

Szostak¹

2017

Mol. Front. J.

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To understand the origin of life on Earth, and to evaluate the potential for life on exoplanets, we must understand the pathways that lead from chemistry to biology. Recent experiments suggest that a chemically rich environment that provides the building blocks of membranes, nucleic acids and peptides, along with sources of chemical energy, could result in the emergence of replicating, evolving cells. The broad scope of synthetic chemistry suggests that it may be possible to design and construct artificial life forms based upon a very different biochemistry than that of existing biology.

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A route to enantiopure RNA precursors from nearly racemic starting materials

Cited by 105 publications

References 25 publications

Prebiotic selection and assembly of proteinogenic amino acids and natural nucleotides from complex mixtures

Prebiotic selection and assembly of proteinogenic amino acids and natural nucleotides from complex mixtures

A Chemical Engineering Perspective on the Origins of Life

The Origin of Life on Earth and the Design of Alternative Life Forms

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