Enzyme-free assembly of DNA-like molecules

US scientists have developed a simple peptide nucleic acid system that self-assembles and adapts to new instructions without enzymes. The study offers new insight into the possible origins of primordial genetic systems and may be useful for future applications such as designing selective catalysts and self-healing biomaterials, say the researchers. 

Test tube systems of self-assembling nucleic acids are nothing new to systems chemistry. However, until now, no one had created an informational polymer that can dynamically remodel its sequence according to selection pressures in an enzyme-free environment. 

Many scientists have suggested that there could have been a primordial genetic system that eventually led to the RNA world. However, ’simple systems on prebiotic earth would not have had the luxury of the enzymes to work on them as they weren’t around to do it,’ says Reza Ghadiri who led the research at the Scripps Research Institute, La Jolla, US. The team therefore aimed to create an adaptive system that could offer a possible solution - without the need for enzymes. 

Ghadiri’s system uses nucleobase building blocks and peptides, which, on their own, are no use for a genetic system. But together, they chemically interact with each other allowing the peptides to form a reversible covalent backbone for the nucleobases to attach to. ’It first forms a complement to the instruction you give it, and then if you throw in a new instruction, it will reorganise and adapt to the new information,’ explains Ghadiri.

’It is extremely intellectually stimulating to see that an informational polymer can be constructed by attaching nucleobase units to a preformed backbone,’ says prebiotic chemist John Sutherland at the University of Manchester. ’All of us tend to think of polymerising units already containing the nucleobases.’

’This work bodes well for systems chemistry where you are trying a bottom up approach of how to build a complex living system or trying to understand what the chemistry of life is,’ says Ghadiri. Although conjecture at this stage, he thinks the work could help towards developing catalysts and drug delivery methods   as well as polymer biomaterials that can dynamically adapt and self-heal.

’It is a beautiful piece of work that demonstrates the plausibility of a dynamic genome, which opens up interesting options for synthetic biology because the bond-forming reactions are potentially easier than the irreversible ones associated with conventional genome replication,’ suggests Sutherland.

’It gets us a step forward toward that goal of achieving a simple chemical system that can autonomously evolve,’ says Ghadiri. He is now working to develop the current system in the hope of getting closer to realising a self-replicating system. ’There is a lot more work to be done but we are inching forward,’ he adds.  

James Urquhart

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