Before LUCA: unearthing the chemical roots of metabolism

The transition from geochemistry to biochemistry marks a fundamental event in the emergence of life. Recent advancements in computational methods and systems chemistry offer new insights into how primitive biochemical systems evolved. While early Earth chemistry laid the foundation for protometabolic processes, linking these to the more complex metabolic capabilities of last universal common ancestor (LUCA) remains a challenge. Here, we propose potential solutions by mapping reaction rules from LUCA's metabolism to prebiotic reactions, enabling the exploration of possible connections between abiotic chemistry and early life. A comprehensive modelling framework is proposed to test these hypotheses, incorporating factors such as thermodynamics, planetary conditions and the availability of key reactants. Additionally, the role of enzyme promiscuity and metabolic evolvability is discussed as a driving force in the transition from early chemistry to life. By leveraging generative models, this research paves the way for future synthetic biology applications, potentially expanding our understanding of metabolism and its evolutionary origins.This article is part of the theme issue 'Origins of life: the possible and the actual'.