A possible non-biological reaction framework for metabolic processes on early Earth

All biological molecules used by living organisms are themselves synthesized by living organisms. The development of routes for making organic matter was therefore an essential early step in the emergence of life on Earth. A complex network of reactions must have arisen to make organic molecules from carbon dio xide, or possibly from other inorganic sources of carbon such as carbon monoxide or cyanides, but the process involved remains largely unknown. In a paper in Nature, Muchowska et al.¹ demonstrate experimentally that a suitable complex reaction network can develop from just two simple organic constituents, namely, glyoxylate (HCOCO₂⁻) and pyruvate (CH₃COCO₂⁻), in the presence of ferrous iron (Fe²⁺).

The identified network produces nine of the eleven main components of the tricarboxylic acid (TCA) cycle — the series of reactions by which present-day organisms metabolize organic matter to convert it into energy (Fig. 1), producing the nucleotide ATP as an energy carrier and CO₂ as a by-product. The TCA cycle can also work in reverse, in which case it is known as the reductive tricarboxylic acid (rTCA) cycle. The rTCA cycle could have been an early route by which CO₂ was converted (fixed) into the organic molecules that are used as the basic components of living organisms. Muchowska and colleagues’ work suggests that the rTCA cycle, as well as other processes that are associated with the metabolism of carbon, could have emerged from a network of abiotic reactions that, at least partly, matched the pattern of the biological reaction network that is now catalysed by enzymes.

The authors also show that, in the presence of hydroxylamine (NH₂OH) and metallic iron, their chemical network can be extended to include the formation of four kinds of amino acid, the building blocks of proteins. Both hydroxylamine and metallic iron could have been available on early Earth: hydroxylamine would probably have formed as a result of the rich, abiotic nitrogen chemistry that is known to have occurred early in the planet’s existence², whereas metallic iron is abundant in certain meteorites that peppered our planet.

Muchowska et al. suggest that their pathway could have developed further to facilitate the subsequent emergence of functional polymers, including peptides and nucleic acids. This would require that abiotic processes that fix CO₂ fed the system with glyoxylate and pyruvate. The authors identify evidence from the scientific literature that supports the existence of such processes, but it is unclear whether these processes could have produced sufficient concentrations of glyoxylate and pyruvate to sustain emergent living organisms. This does not invalidate the authors’ reaction network as a potential key player in the origins of life, however.

We are unlikely ever to know for certain whether present-day processes for metabolizing compounds that contain carbon are a purely biochemical innovation, or are instead derived from a prebiotic chemical network. This is because no remnant of the evolutionary processes involved could have persisted for billions of years. Nevertheless, Muchowska and co-workers’ results strongly support the latter possibility. It seems realistic for a rudimentary biological system to have harnessed a pre-existing network by sharing intermediates, and then for it to have gradually become more efficient by evolving genetically encoded catalysts (such as enzymes that directly facilitate the necessary reactions).

The other possibility is that a full set of enzymes that catalyse the essential metabolic steps emerged from scratch. However, this seems highly improbable, because there would have been no selective evolutionary pressure for this to happen in the absence of a pre-existing, analogous system.

Other general themes have been debated by those working in this field. For example, most researchers reject the idea that life began as the result of a sharp transition in complexity from a mixture of organic compounds to a highly organized, self-reproducing entity that looked like a living cell^3,4. Instead, life is thought to have originated as the result of gradual improvements to an evolving system that were introduced at separate times⁵. In this scenario, the distinction between life and non-life is fuzzy, rather than clear-cut⁶.

Another model builds on the concept of systems chemistry. It suggests that primordial, chemical equivalents of metabolic systems and self-replicating systems could initially have coexisted, but then combined into more-complex systems, perhaps as the result of some kind of compartmentalization process, thereby giving rise to the essential features of life⁷. But it is unknown whether all three components — metabolism, self-replication and compartmentalization — needed to have coexisted before life emerged. Chemists can contribute to these debates by uncovering a wide range of abiotic processes that might feasibly have occurred on early Earth, as Muchowska and colleagues have done. The authors’ reaction network could have integrated into the process of life’s emergence after the appearance of functional polymers, or contributed to the metabolic component in the systems-chemistry model.

The mystery of the origins of life is not simply a question of how the molecular components of biological systems were formed. If that had been the case, then the puzzle would have been solved soon after 1953, when amino acids were identified as the product of an experiment in which electric sparks were fired into a mixture of simple molecules, to simulate the effects of lightning flashes on early Earth⁸.

In fact, the most important aspect of life’s emergence was the first implementation of a ‘physical principle’ for natural selection⁹ — a process by which inheritable improvements can be selected from a population of variants. This, in turn, required molecules or molecular assemblies that can reproduce under certain kinetic constraints, and resulted in the development of a specific kind of stability (known as dynamic kinetic stability¹⁰) that is associated with the dynamics of reproduction. This stability has characterized the living state on Earth for billions of years. Nevertheless, life’s requirement for self-replicating molecules does not mean that the contribution of other molecular subsystems (such as reaction networks) was unimportant, if only because such systems might have needed to reach certain concentrations so that self-replicating systems could emerge.

If research on the origins of life is to reach the next level⁵, several approaches will be needed to provide insight into the process by which life emerged. Identifying abiotic pathways that could have contributed to the overall process is highly valuable, regardless of the stage in life’s evolution at which they were incorporated. Combining systems-chemistry and evolutionary views might be the most productive way forward.