nai

Project Progress

We have made progress in establishing an autocatalytic replication system based on nucleic acids. Initially, we selected a deoxyribozyme ligase that was short enough to be amenable to engineering. We then converted this deoxyribozyme ligase into an allosteric enzyme, a feature that may have been important in the evolution of a metabolism based on nucleic acid catalysts. In order to demonstrate the feasibility of generating autocatalytic replication systems in general, we engineered a ?ping-pong’ cleavage reaction based on a cyclized deoxyribozyme, 10-23. The system demonstrates kinetic behavior that is consistent with autocatalysis and exponential growth. By combining the insights garnered from engineering the deoxyribozyme ligase with those garnered from the cleavase cycle, it should be possible to develop an autocatalytic ligase cycle that may be a milestone in any origins scenario.

Prebiotic replicators and complex catalysts in a putative ribonucleic acid (RNA) world would have segued to peptide-based catalysts. To understand how this may have occurred, we investigated several models for the transition. We have shown that peptides can template the ligation of nucleic acids, and thus may have served as important cofactors in a prebiotic or RNA world. We have also demonstrated that peptides can act as powerful effectors to regulate the activities of nucleic acid catalysts, a function that would again have been important in any complex RNA metabolism.