Ancient enzymes resurrected to take the heat and make better biocatalysts
From animals and entire ecosystems, to building materials and beer recipes, scientists have long drawn on the past for inspiration for new breakthroughs. Now, researchers at the University of Queensland have looked to the past to help with the future of biochemistry, resurrecting enzymes from almost half a billion years ago to fill in where current ones can't.
Whether natural, modified or entirely synthetic, enzymes act as catalysts for chemical reactions, which can be used to produce drugs, food additives, fuels and other chemicals. The problem is, this process isn't necessarily the most efficient way to do things.
"It's often very difficult to make precise changes to complex chemicals, but this is essential in many industries, the pharmaceutical industry being a prime example," says Elizabeth Gillam, an author of the new study. "These methods often attack multiple sites on a chemical, so one ends up with a mixture of by-products, while often requiring a lot of energy and creating harmful waste."
The key to reducing these issues, the team says, is to find enzymes that work at higher temperatures for longer. That allows them to function faster and more effectively for a lower cost, using less energy and not requiring harsh chemicals. Unfortunately, natural enzymes can't handle the heat, preferring a comfortable warmth just above room temperature.
To find the right enzymes, the team looked back in time. Since the Earth was much hotter hundreds of millions of years ago, enzymes that naturally occurred then had to function at those elevated temperatures, which makes them perfect candidates for modern biochemistry. But of course, the problem then is how do scientists get their hands on them?
The UQ researchers started by looking at useful modern enzymes, then worked backwards to determine what they might have looked like some 450 million years ago.
"These enzymes' pre-Cambrian-era-ancestors were able to survive great heat, when temperatures on Earth were around 60° C (140° F)," says Gillam. "We obtained all the gene sequences we could for a particular set of ancient enzymes, worked out their genetic evolutionary history and determined the most likely sequence of their common ancestor that would have existed in the earliest vertebrate animals. Then we recreated this gene, put it into a bacterium and tested the properties of the enzyme it encoded."
When the team edited the gene into E. coli, they found that the new bacteria performed eight times better than the normal bugs at 25° C (77° F), and lasted about 100 times longer. When the team cranked the heat up to 50° C (122° F), it was 3.5 times better than at room temperature.
"This means more 'bang for your buck' in a commercial process, but also improves environmental sustainability, and widens our understanding and use of enzymes in synthetic biology," says Gillam. "The breadth of commercial applications is only limited by the imagination. For example, this discovery could advance fields like gene therapy or help remediate polluted environments – there's a lot of work to do."
The research was published in the journal Nature Catalysis.
Source: University of Queensland