A relatively simple mixture of chemicals can produce some of the compounds needed to form RNA, UNSW scientists have shown.
Scientists from the UNSW Australian Centre for Astrobiology (ACA) and the Earth-Life Science Institute at the Tokyo Institute of Technology have recreated the ‘messy’ conditions that may have given rise to the precursors needed for the formation of life on early Earth.
The scientific field of prebiotic chemistry is the study of the chemistry that might have been important for life’s origins.
“There's a lot of scientists who have looked into how you can make nucleotides, which are the building blocks of DNA and RNA,” says Quoc Phuong Tran, a PhD Candidate from the School of Chemistry. “These syntheses are meticulously designed in a linear reaction. But there is a lack of literature where the process of forming the nucleotides is done in relatively messy environments.”
In a new study, recently published in Chemical Science, Mr Tran and UNSW Senior Lecturer and Director of the ACA, Dr Albert Fahrenbach, found that a type of reaction – known as the autocatalytic formose reaction, which starts from simple reactants that rapidly evolve into a complex mixture – can be manipulated to produce some of the ingredients needed to make RNA.
RNA is important in the context of early life because it is often thought to be one of the first genetic polymers to emerge on early Earth through natural geochemistry that eventually gave rise to life as we know it.
“We know that biology doesn’t do things in a linear fashion but involves far more complex processes. These complex processes typically involve things like autocatalysis,” says Dr Fahrenbach. “The most exciting thing is that this synthesis, at least conceptually, more closely resembles how life carries out synthesis.”
These findings are not only exciting from the point of view of trying to understand how life could have started on Earth, but it also invites researchers to explore new ways of synthesising commercially and medicinally important molecules, in a way that is potentially much cheaper on an industrial scale.
What is autocatalysis?
All cells are like little chemical factories, full of complex reaction networks, but nobody really understands how something as complex as a cell could have emerged on early Earth.
However, we do know that one key aspect for how cells carry out reactions today is called autocatalysis. “Most people are familiar with a catalyst in the sense that it helps other molecules react with each other, that is, they speed up the reaction,” says Dr Fahrenbach. “Think of your catalytic converter in your car – it speeds up the conversion of smog-causing gases into more benign emissions.”
An autocatalyst not only speeds up the reaction, but also makes more copies of itself from the reaction it is speeding up. In effect, autocatalytic reactions are capable of reproducing themselves, like a catalytic converter that produces even more catalytic converters. You can even consider cellular reproduction itself to be a complex set of autocatalytic reactions – a key feature of life.
“Our research shows that this autocatalytic reaction network known as the formose reaction, which produces a range of sugars, can be coerced into making other compounds needed for RNA synthesis. Like DNA, RNA can store information, but it can also carry out house-keeping functions of the cell like proteins do.”
The formose reaction, first discovered in 1861, is one of the best examples of an autocatalytic reaction cycle that could have occurred on the early Earth.
Creating a messy chemical reaction
“A lot of these prebiotic syntheses for making various important biomolecules have been studied using the techniques of traditional organic chemistry,” says Dr Fahrenbach. “Now, that doesn't really apply so well on early Earth, because there was no organic chemist on Earth attending to these reactions.
“One of the most interesting things about this research is that we are using a more messy chemistry approach, messy chemistry meaning complex chemistry.”
Dr Fahrenbach explains that you can think of a cell as one big, complex chemical reactor that isn’t carrying out every reaction in a stepwise process. So the team set out to create an environment in the lab which is analogous to the conditions needed to make the first cells on Earth.
"We created these conditions by adding the components that we're interested in – molecules including formaldehyde and glycolaldehyde, which form the base of the formose reaction,” says Mr Tran. “We then added the third compound, cyanamide, and mixed them together and heated them up.”
Together, the team wanted to track the reaction across time by stopping it every two minutes and using analytical techniques to measure the products at each time point. “We used a process called chromatography, which allowed us to separate out this complex mixture to identify the compounds of the reaction,” says Mr Tran.
“We also wanted measure their concentrations, using something called mass spectrometry, which allows us to detect these molecules by their masses.”
To ensure they were identifying the correct compounds, the team then cross-checked their results by comparing their products to chemical standards.
Harnessing autocatalysis for industrial applications
This work opens the door to further understanding how autocatalysis can be “engineered” to do syntheses more like modern cells do.
“Before this work, many researchers would have thought that the formose reaction and RNA synthesis may have been fundamentally incompatible and could not be directly integrated with each other,” says Dr Fahrenbach.
“The reason this research is so exciting is because autocatalysis is also what’s needed to observe more ‘life-like’ behaviours emerging from relatively simple systems of molecules. Cells can respond to cues from the environment that enhance their ability to navigate and survive. Autocatalysis also allows systems of molecules to respond to environmental cues, as if they were alive.”
Autocatalysis also has the potential to make the synthesis of some pharmaceutically significant compounds cheaper. “Imagine a reaction that autocatalytically produced some important compound needed for a drug. Many compounds rely on ‘normal’ catalysts to carry out a reaction, but what if the reaction also produced the catalyst needed for that reaction?”
The more studies we are able to perfect using autocatalysis, the better we will understand how it can be harnessed to make common chemical reactions more efficient.
“You never quite know what interesting applications will come out of answering fundamental questions, which is why it is so worthwhile,” says Dr Fahrenbach.
“One of the other next steps is to integrate this reaction network inside of a ‘protocell’, a small cell-sized compartment that can help us further understand how life may have emerged under similar circumstances on early Earth,” says Dr Fahrenbach.
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