Skip to main content

Photometabolic Self-Replication

Periodic Reporting for period 1 - PSR (Photometabolic Self-Replication)

Reporting period: 2019-03-01 to 2021-02-28

The transition from non-life to life is one of the most fascinating but challenging issues in contemporary science. It is clear that all the current biodiversity is the outcome of Darwinian evolution from a primitive cellular species, the so-called last universal common ancestor (LUCA). A NASA panel even defined life as a “self-sustaining chemical system capable of Darwinian evolution”. The findings of modern biology have fully validated those principles, but show no illumination of the onset of Darwinian evolution. The design of replicator systems that can evolve will advance our understanding of the chemical roots of Darwinian evolution and its origin, and pave the way for de novo synthesis of life.
Direct kinetic or thermodynamic selection can be imposed on some synthetic replicators, where the selection targets are physicochemical properties rather than “encoded” functions like in biological evolution. To make the selection coherent with the Darwin framework, functions should be coupled to mutations to enable selection of functional advantage. An organizational logic of an ensemble of higher-order processes (e.g. through a compartment) is required to keep the replicator together with its corresponding functional components for retaining the metabolites for the benefit of the replicator that produced them.
Systems chemistry dealing with intricate combinations of molecules (e.g. via reaction networks, self-assembly, and self-organization) at once will help address many of the challenges in evolutionary chemistry, leading to the emergence of evolutionary systems chemistry. The objectives of the project are to functionalize replicators by integrating metabolism and build up a self-maintaining chemical replicator systems capable of Darwin evolution and adaption.
Photocatalytic cofactors were designed to promote the thiol oxidation reaction to facilitate the emergence of replicators based on photocatalysis. Replicators capable of photometabolism were obtained, which breaks new ground by, for the first time, integrating replication with a rudimentary form of metabolism. This part of the work has been published in Nature chemistry (DOI: 10.1021/jacs.8b11698) that is the most influential journal in chemistry. Chemical and Engineering news (C&en) ( Phys. Org ( EurekAlert ( SCIENMAG ( C2W ( N+1 ( have highlighted our work in their magazines. It was also selected as key development in 2020 by Chemistry World (

A two-replicator system was developed and investigated under photocatalytic flow conditions. Replicators can not only integrate metabolism for self-replication but also use it to tune the oxidation level of the system, constructing ecological-evolutionary feedbacks to make the replicators adapt to the change of light intensity.

Mutant replicators (i.e. mixed hexamer) were also investigated under photocatalytic flow conditions. The replicators can evolve and adapt to a change of environment (e.g. organic cosolvent, high oxidation level), resulting in the shift of the replicator distribution away from the statistical control determined by the building block ratio, generating order and information from randomness.

The mutant replicators bound with cofactors provide a functional space for the evolution of photocatalytic activity. Far from equilibrium selection favors the replicators with higher catalytic efficiency based on the following mechanisms: inhomogeneous distribution of “food” selectively benefits the replicators that are most efficient at producing it and enough fidelity. The replicators can be selected based on their function (i.e. in a Darwinian sense) due to this higher-level organization.

The results of the above research have been presented at Simons meeting (New York, 2019, USA) and three on-line conferences (Systems Chemistry Virtual Symposium 2020, Molecular Origins of Life 2020, Chains 2020).
Energy consumption was considered to be integrated into the process of self-replication, which may provide an alternative strategy to operate replicators out of equilibrium. A metastable molecule was designed to act as a chemical effector to select between competing self-replicators. We are now trying to use the molecule to maintain the non-equilibrium steady state of the replicator by continuous addition of the template. Such system integrates chemical energy-fueled self-assembly with self-replication.

Active amide droplet was developed. Besides transient structure another emergent behavior was found: the directed motion of the droplets towards oleic acid was found at the time scale of hours and a length scale of several hundred micrometers. This system is promising to bottom-up integrate multiple life-like behaviors (e.g. energy consumption and dissipation, dynamic self-assembly, reproduction, motion) from the molecular to macroscopic level, which are bringing closer the dreams of the synthesis of life and the unraveling of the chemical foundation of life.