Going to Extremes to Find Greener Chemicals
Next time you watch a TV program that cracks a crime using DNA evidence, tip your hat to the microbe that makes it all possible.
That molecular sleuthing using DNA samples owes its success to an enzyme from a heat-loving bug that hangs out in hot springs and thermal vents. Because the enzyme can withstand high temperatures, we can use it in cycles of chemical reactions that multiply tiny amounts of DNA up into useful quantities, much like a molecular photocopier. Then the DNA can be sequenced and, hopefully, the crime can be solved.
It’s an example of how the adaptations of extremophiles that happily live in seemingly harsh environments can inspire useful chemical processes, and UCD researcher and Conway Fellow, Dr. Francesca Paradisi is on the case.
Her approach looks at halophile organisms that can live in high salt concentrations such as the Dead Sea, and she’s working out whether some of their enzymes could help make chemical processes in industry greener.
Paradisi, who studied chemistry at Bologna in Italy, wasn’t familiar with extremophiles before she came to UCD to work with Professor Paul Engel just after she finished her PhD. But when she saw what his group was doing, she was intrigued by the possibilities.
Now a college lecturer at UCD School of Chemistry and Chemical Biology, she has built up her own team and they have been meticulously screening various halophiles for a type of enzyme called alcohol dehydrogenase (ADH).
It’s an enzyme that many organisms - including ourselves - produce naturally, and it is used in chemical processes in the food and pharmaceutical industries. So why might an ADH from a salt-loving organism be particularly useful?
“The idea is that enzymes that are produced by these halophiles, due to their particular high-salt environment, will be more likely to adjust to a solvent situation - when you have high salt you have less water around the enzyme,” Paradisi said.
The trick is to find enzymes that tick several boxes: they are easy to purify from the organism, they are stable so they don’t need too much cosseting and their special properties can make a range of chemical processes greener.
So Paradisi’s team has been cloning, isolating and analyzing various ADH enzymes from three types of halophile to see what kinds of talented enzymes they produce naturally.
The lab has been focusing on three main organisms: Halobacterium salinarium, Haloarcula marismortui and Haloferax volcanii, explains Dr. Paradisi, but the initial work has been difficult because so little is known about how to purify the proteins.
However, despite the newness of the area, already they are turning up promising candidate enzymes, and soon the group will publish the first of the findings in the journal Extremophiles.
Their approach is also attracting the interest of industry: Dr. Paradisi’s group has an ongoing collaboration with Spanish biotech company Arquebios, and she is in talks with other potential partners.
She stresses that the organisms used in this process are safe.
“These organisms are completely harmless, and they are generally growing in a highly-salted environment so as soon as you put them in water in the sink they burst,” she said.
So what is the ultimate goal? To develop a system where a specially engineered bug can produce useful amounts of one or more useful enzymes like a biological printing press, explains Dr. Paradisi, whose work has received funding from the Environmental Protection Agency, Science Foundation Ireland, IRCSET and Merck.
“Enzymes are a little different from small chemicals that you would find in nature - they are quickly reproduced and we can clone them,” she says. “So we are looking to use a host cell that can be engineered in such a way that it produces a higher amount of the extremophile enzymes.”