Summary of the project

Life on Earth constitutes a historical process that developed by complexification starting from chemical systems. It is considered in this project that physico-chemical driving forces and contingency are responsible of this process since its early beginning. Theoretical aspects will constitute both the starting point of this project and a matter of investigation to contribute to a better understanding of the physical origin of complexity. Within this perspective, the emergence of protometabolisms defined as networks of chemical reactions proceeding under far from equilibrium conditions and involving nonlinear features and therefore being capable of generating self-organisation (associated with a local decrease in entropy compensated by the irreversibility of the overall process) is a key step for the origin of life. Chemical networks of this kind must work as unidirectional sequences of reactions or preferably as unidirectional reaction cycles in which a further process of positive chemical feedback would be capable of generating systems endowed with autocatalytic properties and then behaving in a nonlinear way. Determining which pathways could have constantly or repeatedly fed these systems with energy to maintain the far from equilibrium state is then essential to understand how self-organisation could emerge. This approach is applied to the formation of biopolymers capable of functional activities that is generally considered as a prerequisite for the origin of life. Our original goal is to propose an overall scenario integrating the formation of peptides and other related processes to build a network capable of giving rise to emergent properties related to the connections of the different parts of the network. The project is aimed at understanding how peptides could be formed under prebiotic conditions and how energy sources could have been coupled to peptide bond formation. But it is not limited to this goal since random peptides made from racemic mixtures of amino acids are unlikely to adopt definite structures needed for specific activity so that it will address the question of the emergence of selectivity (and stereoselectivity) or that of improbable but dynamically stable states. Lastly the emergence of translation at an early stage of evolution suggests that the chemistry of amino acids and peptides can be coupled to that of an information carrier supporting the hypothesis of a peptide-nucleotide co-evolution. All these topics will be experimentally investigated by monitoring the reactions through common methods of analytical chemistry and organic chemistry (NMR, HPLC, MS, UV…).

Objectives of the proposal

The origin of life and that of the Universe are usually considered as the most fundamental questions open to science, these issues raise a broad interest and attract a large audience. Moreover, the issues of the origins of life and that of the creation of artificial cells from scratch have been considered as belonging to the most important to be resolved in the future of chemistry. Bringing new answers to the question of the origin of life would mean that the principles and the specificity of the living state are now well understood. By bridging chemistry and biology, the latter could be integrated into physical sciences on the grounds that its main tenets are explained in terms of lower level concepts, which puts chemistry at a central role for this goal. It is the science that can address the issue of the origins and specificity of life provided that it focuses its attention on kinetic processes involving reproduction (or autocatalysis) and thus in which events occurring at the scale of a limited number of atoms or molecules can have macroscopic consequences, which is not the common way of thinking in chemistry.

Our project is aimed at contributing to develop an overall view of the amino acid chemistry that could take place in prebiotic environments. It starts from theoretical considerations on the thermodynamics and kinetics of metabolic and protometabolic systems supporting the living state and its origins, respectively, and comes to an end with detailed reaction paths that may have been involved in this evolution. As achieving exhaustively this task would require a huge amount of work, we selected a series of pathways for which we got preliminary indications that they could be of importance with respect to our project. Additionally, less documented topics will also be investigated to give new directions for further research. This project is quite unique in the European and international context since it brings together scientists who have played an important role in prebiotic peptide and nucleotide chemistries during the recent years and who have the expertise needed to investigate complex reaction systems that can be orientated towards different directions depending on reaction conditions. It is based on a non-exclusive co-evolutionary view of the origins of life. This view merges on the one hand the indications provided by the investigations performed after the Miller experiment on the possible synthesis of organic matter in the atmosphere of the early Earth and the analyses of meteoritic organic matter suggesting that amino acids were abundant on the early Earth and on the second hand the important role of RNA at early stages of life, which supports a stage of evolution named “RNA world”. It fully agrees with the concepts supporting Systems Chemistry. A chemistry of α-amino acids and peptides interacting with nucleotides on the early Earth required that all these biomolecules could be formed in the environment or delivered from space as components of meteorites or micrometeorites. Though a pool of amino acids could have accumulated from these processes, the developments show that activation pathways were needed since highly activated molecules could not have been conserved as such in the parent bodies of meteorites during periods of several hundreds of million years before their delivery to the Earth. Then processes capable of directly providing activated precursors (hydrogen cyanide, cyanamide, cyanoacetylene or other similarly activated species) or of activating pre-existing biomolecules were needed to trigger the development of a proto-metabolism. The originality of this project is to address these issues in a context where both the physicochemical requirements are considered and in which information on the reasonable character of the chemical paths considered is available from the earlier studies from the partners or in the literature. An exhaustive study of these systems would be non realistic with regards to our possibilities, but crucial pieces of information on the validity of the scenario may be obtained by developing earlier studies. We concentrate our efforts on the formation of cyanamide (or alternative reagents) through the photochemistry of transition metal complexes, on the activation of peptides using this reagent, on the nitrosation of carbamoyl amino acids in the coordination sphere of transition metals, on the stereoselectivity and epimerization of peptide activation, on the stereoselectivity of the peptide cleavage. A success in these investigations would result in unravelling new pathways providing new information on the possibilities of prebiotic chemistry. However, since this study considers the Systems Chemistry of the network, our investigations are also aimed at determining if these processes, considered as a whole, are capable of leading to steady states corresponding to a higher organisation degree than the equilibrium state and that are made kinetically stable by the delivery of energy.