Sometimes in biotech, when your standard E. coli just won’t cut it, something more exotic is needed. Could extremophiles be the answer?
Given enough time, and the right mutations, life can adapt to thrive in even the most seemingly inhospitable environments. From volcanic hot springs to hyper-saline soils, microbes have made their homes pretty much everywhere that offers some kind of resource to exploit. But these ‘extremophiles’ (literally, ‘lovers of extremes’) aren’t just fascinating quirks of evolution – their hardiness and unusual metabolic abilities have made them increasingly valuable to the world of biotechnology.
Extremophiles have already had some notable impacts on modern bioscience. One of the most essential laboratory procedures in molecular biology, PCR (Polymerase Chain Reaction), which enables scientists to make copies of target segments of DNA, utilizes a heat-stable enzyme called Taq polymerase, isolated from Thermus aquaticus, a species of bacteria discovered in the hot springs of Yellowstone National Park. It is hard to overstate just how powerful and indispensable a tool PCR has been in molecular biology, and for its contribution, Taq polymerase was named ‘molecule of the year’ in 1989 by the journal Science.
So what’s next for extremophiles? I spoke to several European biotechs working with these consummate survivors to find out.
Decontamination of chemical weapons
Organophosphorous compounds are infamous for their toxicity. Commonly used as pesticides, they’ve also been turned into highly potent and deadly chemical weapons. These include the nerve agents sarin, deployed most recently in the ongoing Syrian civil war, and VX, used in the 2017 assassination of Kim-Jong Nam, exiled half-brother of the North Korean leader.
Governments across the globe are understandably keen to find new ways of rapidly and effectively degrading such toxic compounds, and by looking to extremophiles, Gene & Green TK believes it has found a solution.
The Marseille-based biotech was founded in 2013, emerging from research carried out at Aix-Marseille University in collaboration with the French Defence Procurement Agency with the aim of finding and developing highly robust enzymes capable of breaking down organophosphates. Its flagship product, VesuTOX, utilizes an enzyme called SsoPox, discovered in an extremophilic archaea, Sulfolobus solfataricus, living in volcanic pools near Mount Vesuvius.
“This extreme environment conferred a tremendous robustness to the enzyme, allowing it to resist various harsh conditions,” David Daudé, Gene & Green TK’s Chief Scientific and Operating Officer told me.
“A directed evolution approach was driven in the laboratory to increase its efficiency for the degradation of most organophosphorus compounds in a few minutes.”
The enzyme-based VesuTOX solution enables rapid, safe, simple, and environmentally friendly decontamination of organophosphorus weapons and insecticides. It can be incorporated into filtration systems, applied to materials and equipment, and can even be used on skin in the form of a spray or shower as it has no innate toxicity and is biodegradable.
“VesuTOX offers a very promising alternative to the conventional chemical solutions, sodium hydroxide and bleach, that are corrosive and not safe for application on humans,” Daudé explained.
“We have exhaustively demonstrated the efficacy of our technology in the lab and validated the proof of concept. Our efforts… have led to the development of a decontaminating spray that now needs to be certified according to NATO recommendations.”
Boosting crop health
The global agricultural sector faces a major challenge for the 21st century: maximizing productivity to feed a growing population while also reducing dependence on agrochemicals like synthetic fertilizers and pesticides, which are increasingly recognized as unsustainable in the long term.
Xtrem Biotech, a spin-out from the University of Granada, is developing agricultural probiotics to address this challenge, based on extremophile plant-boosting soil bacteria. Its extremophile of choice is a strain of Bacillus referred to as XT1, originally isolated from hyper-saline soils in southern Spain.
The bacteria’s knack for tolerating difficult conditions, not just high soil salinity, but also drought, extreme pH levels, and exposure to UV radiation, means that it can survive for a long time in the soil in stasis when the conditions aren’t appropriate. It is then able to reanimate when the conditions are more optimal, as well as being easily stored and transported.
But it’s the microbe’s ability to stimulate plant growth and protect against pathogens that makes it such a promising alternative to agrochemicals. XT1 produces a range of metabolites that promote crop health, including amino acids and sugars that the plants can use for growth, auxins which increase root formation, and a variety of antimicrobial compounds that can protect against fungi and other plant pathogens.
“Typically efforts to control these problems utilize strong chemicals that follow a ‘scorched earth’ mode of control, killing everything, both good and bad microbes,” said Borja Torres, CEO of Xtrem Biotech.
“Effectiveness [of XT1 compared to agrochemicals] is similar or better if used correctly, not in the same way as chemicals but in a preventive way. It is important to underline the fact of sustainability and safety for users and the environment, where biologicals are far ahead of chemicals.”
Xtrem’s XT1-based biostimulant, Heroprotec Micro, has already been trialed on tomato, pepper, pumpkin, cucumber, courgette and strawberry crops, achieving encouraging results.
“After five years of development and field trials its efficacy is well determined,” Torres explained. “The immediate target on the horizon is to gain a commercial agreement with an established partner to advance in the regulatory process and consider a sublicense of the technology, which will allow us to go further in the development of new products and strains.”
Production of anti-aging molecules
French biotech Deinove has an enviable collection of thousands of species of rare microbes that the company has been collecting since it was founded in 2006. Deinove’s ever-expanding microbial library is constantly being screened to identify strains with useful properties, leading to several promising extremophiles being singled out and developed for a range of applications, including the production of new anti-infective and bioactive compounds.
Deinove’s most advanced product is Phyt-N-Resist, an anti-aging agent for the cosmetics industry, made possible by the isolation and development of an extremophile called Deinococcus geothermalis, collected from the volcanic hot springs of Reunion Island, a French territory in the Indian Ocean.
“To resist such extreme conditions they have developed the means to defend themselves. They notably produce special compounds, for example carotenoids, which are ‘natural shields’. These molecules can be extracted to transpose these resistance properties to skin, which is also facing stress factors like air pollution and UV radiation.” Emmanuel Petiot, CEO of Deinove told me.
Phytoene, the original precursor of all carotenoids, has been shown to have remarkable antioxidant properties, preventing cellular degradation and ultimately, skin aging. But humans don’t naturally produce it in our skin, and before Deinococcus geothermalis was harnessed there wasn’t an effective method of extracting pure Phytoene for commercial use. The microbe’s ability to efficiently synthesize protective carotenoid molecules – vital for its survival in the wild – made it a prime candidate for a new phytoene bioproduction platform.
“Deinococcus is a perfect fit, provided you master this bacterium like we do,” said Petiot.
“The major challenge was to orient our strain towards hyperproduction of phytoene, in order to provide the first pure highly concentrated phytoene to the market.”
It’s clear that extremophiles are continuing to broaden biotech’s horizons, yet we’ve only seen the smallest snapshot of what nature has to offer. By some estimates, there may be over one trillion microbial species on earth, with 99.999% of them still undiscovered.
Exploring that staggering biodiversity will be a never-ending effort, but probing the most hostile habitats could uncover a wealth of resourceful and tenacious extremophiles whose talents can be harnessed for further applications beyond the capability of most other forms of life.
Photo Credits: Gene and Green TK, Xtrem Biotech, Deinove.