Prebiotic chemistry

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.

It’s generally assumed that primitive forms of cellular life arose from nucleic acids and peptides compartmentalized within vesicles — all underpinned by a non-enzymatic protometabolism. Three studies now provide new insights into the ancient chemistry that may have supported early biology.

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.

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.

It is unclear how phospholipid membranes formed on the early Earth, as modern cells synthesize the phospholipid constituents of their membranes enzymatically. Now, a combination of ion pairing and self-assembly has enabled transacylation of lysophospholipids with acyl donors in water, affording a variety of membrane-forming natural diacylphospholipids in high yields.

The integration of replication with metabolism represents a key step in the transition of chemistry into biology. Now, it has been shown that a self-replicator can recruit and activate two different photocatalytic cofactors, which then catalyse the synthesis of the precursors for the replicator.

It’s not known how life’s essential properties of replication, metabolism and compartmentalization were first integrated. Two recent articles now shed light on how metabolic characteristics may be incorporated into replicating systems, harnessing an external energy source to increase their rate of replication and acquiring catalytic activity.

Asymmetric autocatalysis—such as that observed experimentally in the Soai reaction—may have been responsible for the origin of biological homochirality. The magnitude of the energy imbalance required to induce directed symmetry breaking and asymmetric amplification in the Soai reaction has now been identified and compared to the parity violation energy difference.

The emergence of pristine RNA and DNA on the early Earth would have been hindered by a lack of specificity in their prebiotic syntheses. Now, it has been shown that chimeric sequences—with a mixture of RNA and DNA backbones—mediate the template-directed ligation of oligomers present in mixtures of nucleic acids, enabling the simultaneous appearance of RNA and DNA.

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.

RNA is usually considered to be the first genetic polymer, with DNA a product of a biochemical pathway that arose after the origin of life. Now, studies into the prebiotic phosphorylation of an RNA nucleoside reveal pathways for the synthesis of DNA building blocks, providing experimental support for a prebiotic link between RNA and DNA.

The simplest sugar—glycolaldehyde—has recently been detected in space and now a mechanistic rationale for its formation is presented, which includes its onward reaction to the next higher aldose, glyceraldehyde. The key species in the chemistry at play is the formaldehyde isomer hydroxymethylene, which reacts with the carbonyl component in an essentially barrierless carbonyl–ene-type reaction.

Phosphorylation of (pre)biological molecules in water has been a long-sought goal in prebiotic chemistry. Now, it has been demonstrated that diamidophosphate phosphorylates nucleosides, amino acids and glycerol/fatty acids in aqueous medium, while simultaneously leading to higher-order structures such as oligonucleotides, peptides and liposomes in the same reaction mixture.

There are many unanswered questions regarding how the biomolecules and biomechanical processes that define life came to be. A collection of Articles in this issue show how intermediates in RNA synthesis might have formed and how the initiation and evolution of RNA replication might have occurred.

A collection of articles in this issue focuses on the chemical origin of life — how simple molecules present on the early Earth could have evolved into the complex dynamic biochemistry that we know today.