(Santa Barbara, Calif.) — The enigma of how life originated from Earth’s primordial soup has captivated scientists for generations. Researchers at UC Santa Barbara have now made a significant breakthrough, discovering that certain naturally forming droplets could have played a crucial role in the development of complex biochemistry. Their findings, published in the Proceedings of the National Academy of Sciences, suggest that these droplets promote essential redox reactions, potentially acting as proto-enzymes that facilitated the formation of more intricate organic molecules.
“We developed a method to peer inside biologically important liquid droplets using electrochemistry, allowing us to understand how they create a conducive environment for chemical reactions,” explained Nick Watkins, co-lead author and former postdoctoral researcher in Professor Lior Sepunaru’s lab. This research is a continuation of work by UCSB professor Herbert Waite and a long-standing collaboration with Professors Daniel Morse and Mike Gordon on protein assemblies, supported by a MIRA grant from the National Institutes of Health and UCSB’s Stanley and Leslie Parsons Fund in Biochemistry.
Understanding the Chemistry
At the heart of this research lies a fundamental question about the chemistry that might have occurred on prebiotic Earth. The hypothesis suggests that early organic chemistry took place within small droplets, known as coacervates. “These droplets can be likened to oil droplets in water,” Watkins noted. However, unlike oil, coacervates form from macromolecules such as proteins, RNA, or other polymers that coalesce within a solution.
Sepunaru, Watkins, and co-lead author Gala Rodriguez aimed to determine whether coacervates create an environment conducive to biologically significant reactions. They focused on redox reactions, which involve the transfer of electrons between substances. These reactions are vital, comprising about a third of all biochemical processes and often underpinning energy pathways in living systems.
Exploring Micro-Environments
The team sought to replicate an environment that might have existed on early Earth by using an RNA molecule (polyuridylic acid) and a peptide (poly-L-lysine) to create their coacervate. Instead of using complex biochemical reactants, they opted for the reduction of ferricyanide to ferrocyanide, a well-documented redox pair in chemistry. “It’s a textbook reaction you learn about in redox chemistry,” Sepunaru remarked.
By measuring the coacervates’ Gibbs energy through voltage, the researchers could gauge the spontaneity of the reactions. “The voltage you’re measuring from a redox reaction is linearly proportional to Gibbs energy. In some way, we can think about electrochemistry as a Gibbs energy meter,” Sepunaru explained.
Revealing a Different Environment
The study revealed that the environment within the coacervate increased the likelihood of redox reactions occurring spontaneously. While previous research has shown that these droplets facilitate such reactions, this study is the first to elucidate how the micro-environment drives these changes. “We demonstrated that the water surrounding the iron behaves differently inside the droplet than in ordinary water,” Sepunaru stated.
“Beyond finding that the droplets’ internal environment makes redox reactions more likely, we also found that molecules have an easier time donating electrons within this unique environment,” said Rodriguez, a doctoral student in Sepunaru’s group.
Most researchers believed coacervates served merely as tiny reaction chambers concentrating reactants. However, this study reveals a change in Gibbs energy within the microenvironment, altering the probability of reactions occurring independently. “Inside these droplets, the chemistry is very different from normal water,” Sepunaru explained. “This is crucial for understanding the origin of life.”
The Role of Proto-Enzymes
The researchers consider coacervates as proto-enzymes because they actively catalyze reactions, similar to enzymes. While enzymes are complex and highly evolved proteins, coacervates are naturally occurring droplets with simpler chemistry. By functioning as proto-enzymes, coacervates could have enabled the emergence of more complex bio-molecules.
Future Directions
Sepunaru acknowledged the challenges faced during the project, with several false starts before Watkins and Rodriguez successfully tackled the issues. “It took a lot of innovation and creativity on their part to actually solve the problems,” he said.
While Gibbs energy indicates which reactions are likely, it does not always correlate with reaction speed. However, in electron-transfer reactions, the class of redox reactions studied, Gibbs energy and reaction rate are linked. The team plans to explore how coacervates influence reaction speed and to investigate more complex redox reactions.
“A lot of teams have their instruments trained on coacervates. But we’re the only lab with our eyes on the Gibbs energy,” Sepunaru noted.
This groundbreaking research not only sheds light on the potential origins of life but also opens new avenues for understanding the fundamental processes that underpin biochemistry as we know it.
