I2SysBio researchers propose how to bridge the gap between the origin of life and the metabolism of the last universal common ancestor
Juli Peretó and Pablo Carbonell, researchers at the Institute for Integrative Systems Biology (I2SysBio), a joint centre of the University of Valencia (UV) and the Spanish National Research Council (CSIC), put forward a strategy to trace back from the last universal common ancestor (LUCA) to the origin of life. The study, published today in the journal Philosophical Transactions of the Royal Society, applies the approach of generative metabolism, a methodology from synthetic biology that uses artificial intelligence algorithms to extrapolate LUCA’s metabolic capacities into the past.
2 de october de 2025
Pablo Carbonell, CSIC research scientist, emphasises that “our proposal is based on generative metabolism methodologies, which have a proven track record of success in the field of synthetic biology and metabolic engineering”. “The novelty lies in the fact that these techniques can be applied to one of the great unresolved questions of early life evolution: how LUCA’s complex metabolism first emerged”, highlights Juli Peretó, also professor of Biochemistry and Molecular Biology at the UV.
The paper argues that generative metabolism models, based on sets of reaction rules, open up a promising path for exploring enzymatic evolution within an expanded metabolic space that includes both currently existing metabolic reactions and those that would have been possible under certain environmental conditions. “By understanding this full range of possible reactions, we can make more detailed hypotheses about the origins of life”, the researchers point out.
One of the classic problems in the study of early life evolution is how the transition took place from prebiotic chemistry (before the appearance of life), on a planet very different from today’s, to the most primitive metabolisms that eventually made the evolution of the first microorganisms possible. Until now, the combination of bottom-up approaches (from chemistry to biology) and top-down approaches (from present-day metabolic diversity back to LUCA) had been unable to bridge the gap between the prebiotic world and LUCA.
“It is possible to trace enzyme evolution back through the tree of life to LUCA, and to map the ancestral genes that LUCA likely possessed together with their corresponding sets of encoded reactions”, explain Carbonell and Peretó. Using methodologies derived from generative metabolism, the authors propose that the sets of reactions observed today can be rewound to the prebiotic reaction networks associated with the very beginnings of biological evolution.
The article forms part of a special issue of Philosophical Transactions of the Royal Society B devoted to the theme “Origins of life: the possible and the actual”, which includes some of the contributions presented at a symposium of the Santa Fe Institute, coordinated by Ricard Solé (ICREA, Institute of Evolutionary Biology CSIC-UPF), Chris Kempes (Santa Fe Institute) and Susan Stepney (University of York).
Reference: Carbonell P., Peretó J. (2025). Before LUCA: unearthing the chemical roots of metabolism. Phil. Trans. R. Soc. B 380: 20240292. DOI: 10.1098/rstb.2024.0292
Annex caption: Cover image of the special issue of the journal Philosophical Transactions featuring the article “Before LUCA: unearthing the chemical roots of metabolism”.