University of Groningen
Self-Replication out-of-Equilibrium
Yang, Shuo
DOI:
10.33612/diss.171627402
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Publication date:
2021
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Yang, S. (2021). Self-Replication out-of-Equilibrium. University of Groningen.
https://doi.org/10.33612/diss.171627402
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Summary
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Summary
In this thesis, we employed synthetic self-replicating systems attempting to mimic and understand life’s central characteristics including diversity, out-of-equilibrium states, complexity and homochirality.
In chapter 2 we reported on the emergence of two new self-replicators (pentamer and trimer) arising from building blocks that normally assemble to replicate in the form of a hexamer. TEM imaging confirmed the formation of fibers assembled from pentamer and trimer. Based on optical measurements we speculated that the addition of guanidinium chloride strengthened the hydrophobic interactions between the building blocks, therefore altering the size of the macrocycles that self-replicate. Cross-seeding experiments between hexamer, pentamer and trimer showed very limited extents of cross-catalysis. Taken together, with a change in environment using guanidinium chloride, we were able to obtain differently-sized self-replicators from a common building block.
In order to implement redox reactions in self-replicating systems, research in Chapter 3 was focused on the kinetics of redox and exchange reactions in thiol-disulfide chemistry at different pHs. The results showed that all of these reactions slow down as the pH is decreased and the rates of these reactions follow order: reduction > exchange > oxidation. The reduction of disulfides mediated by TCEP is more rapid than oxidation of thiols by NaBO3. Notably, our
kinetic data showed that disulfide exchange was still active at low pH conditions. The kinetic study provided a good foundation to setup out-of-equilibrium conditions in self-replicating systems.
The discovery in Chapter 2 and the kinetics study in Chapter 3 led to the investigation of out-of-equilibrium systems in Chapter 4. We showed that, when a system of replicators was subjected to a regime where replication competes with replicator destruction, simple and fast trimeric replicator can give way to more complex and slower hexameric replicator. An out-of-equilibrium state where disulfide-based replicators form and break continuously was achieved through constantly supplying oxidant and reductant. Due to the complexity of the system, which consist of multiple interconverting species with their own kinetics, computational studies were utilized to perform a flux analysis supplementing experimental observations. Furthermore, the structurally more complex replicator was found to be functionally more proficient in the catalysis of a model reaction. These results showed that chemical fueling can maintain systems of replicators out-of-equilibrium, populating more complex replicators that are otherwise not readily accessible.
In Chapter 5 we reported on the emergence of a self-replicator with homochirality. The pentameric self-replicator obtained in Chapter 2 exhibited high chiral selectivity proven by
seeding experiments and mass analysis. Mixing building blocks with different chirality only resulted in heterochiral replicating trimer. While upon adding pre-formed pentamer as seed, the homochiral pentameric self-replicator grow from the racemic mixture by only consuming building block with the same chirality. The results suggest that biochirality might emerge in multiple stages where the very first simple forms of life can self-replicate in a heterochiral manner and homochirality is introduced at a later stage in evolution.
Summary
