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Friday, December 7, 2018

On the hunt for fungi that could save lives -- and the planet

She studies the soil, the trees and their roots in search of fungi, because long walks like these are actually part of her job. She regularly ventures out in hope of discovering new fungal species hidden deep in the dirt or high among the trees.
"We want to collect as many diverse species of fungi as possible," said Landvik, a mycologist -- a fungi scientist -- at the biotech company Novozymes. "Diversity is really the key word for everything that we do."
Mycologist Sara Landvik forages in Hampstead Heath, London, looking for new species of fungi that could one day have industrial applications.
The organisms have a plethora of applications that can benefit humankind in the production of food and alcohol, drugs, biofuels, washing detergents and even a famous childhood toy: LEGO.
Their nutritional value shouldn't be overlooked, however. There are about 350 species of edible fungi. With vitamin D, glutathione and ergothioneine, they can reduce oxidative stress linked to diseases such as cancer, heart disease and dementia.
Fungi are unique beings, Landvik explained. "They're so different from plants, and they're so different from animals. They are their own kingdom. The evolution of fungi has radiated into so many different directions. They are really, really, amazing."
The best estimate is that there are as many as 3.8 million species of fungi worldwide -- though only about 144,000 have been discovered, according to this year's State of the World's Fungi report, compiled by staff members at Royal Botanical Gardens, Kew, and several others.
New ones are found by searching forested areas, collecting soil samples and bringing the samples back to the lab to be studied, Landvik says.
But the real skill is understanding how they work.
In the wild, fungi are not able to move, so they compete against other fungi or bacteria for resources and, in doing so, produce toxic chemicals. In some cases, these chemicals have been useful to humans.
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Once samples reach the laboratory, Landvik says, they are grown inside a Petri dish and cut into pieces, which are then put into a flask with a liquid of nutrients such as minerals and vitamins and a carbon source to help the fungi grow.
Fungi grow by secreting enzymes -- proteins that catalyze or speed up chemical reactions -- which are captured by the liquid inside the flask, allowing them to be studied in-depth.
Thousands of fungi are studied before researchers stumble upon one that could have an application, Landvik said.
It's like a "lottery ticket," she says, as each discovery could turn up "something that can make a difference in the world, something that we can make a greener industry possible, and so on."
For example, one of Landvik's colleagues came across an enzyme that can be used to reduce the formation of the chemical acrylamide, which forms when starchy food is baked or fried and can be carcinogenic. By searching a database for homologous gene sequences she found sequences for asparaginase, also the name of the enzyme, and soon saw that many fungi contain this enzyme. One of them went on to become Acrylaway, a solution that reduces acrylamide formation in food products processed at high temperatures, which the company say can cut acrylamide formation by up to 95%.
More famous is the discovery of penicillin in 1928, discovered when Alexander Fleming was sorting out his Petri dishes after a holiday and saw a blob of mold had grown with a clear zone surrounding it, later found to be a strain of Penicillium notatum.
How we search for useful enzymes 90 years later is still down to serendipity.
Penicillin was discovered by Alexander Fleming in 1928.

'Evil puppetmaster'

Tom Prescott, a research leader at Royal Botanical Gardens, Kew, in the UK, also notes the many useful applications of fungi.
"Broadly speaking, the three big topics are perhaps medicines, biotechnology and, in the broadest sense ... fungi are really good for eating," he explained, standing in Kew's fungarium, a large room filled with rows of boxes housing 1.25 million specimens of fungi from all around the world, including specimens collected by John Ray, Charles Darwin and Alexander von Humboldt.
Tom Prescott in the fungarium at Royal Botanic Gardens Kew, which holds approximately 1.25 million specimens of fungi.
People are discovering fungi on a yearly basis, Prescott told CNN. "This is everything from fungi that you could see with the naked eye all the way down to microscopic fungi that you perhaps wouldn't know they were there but we detect them using DNA."
Some famous examples of medical applications are the cholesterol-lowering drug lovastatin, produced by the Aspergillus terreus fungus, or a hepatitis B vaccine that is made using yeast.
The drug fingolimod -- used to treat the autoimmune disease multiple sclerosis -- is derived from an eye-catching "zombie" fungus, Isaria sinclairii, that invades an insect, takes it over and eventually acts like an "evil puppetmaster," controlling the insect's body and behavior to perform tasks that are advantageous for the fungus, Prescott said, holding a a boxed sample of the fungus in action.
Meanwhile, the insect is kept alive, "so it's really gruesome," he said. "It's crucial that the fungus doesn't kill the insect initially but does keep it alive, so that's why it produces an immunosuppressant chemical." This chemical is myriocin, which also suppresses the human immune system.
The multiple sclerosis drug Fingolimod, derived from chemicals produced by the insect-invading fungus Isaria sinclairii.
"A lot of fundamental biochemistry and even immunology is shared, surprisingly, even between insects and humans," he explained.
Fungi are also useful in converting one chemical into another, such as in the production of vitamin B tablets.
There has been competition between human chemists and fungi over which is better at producing these pills, and the fungi turned out to be a more cost-effective option, Prescott said.
A Cordyceps fungus invades a cricket to grow.

Saving the environment

About half of all commercially used enzymes are derived from fungi, Shauna M. McKelvey and Richard A. Murphy write in "Fungi: Biology and Applications." The book cites the enzymes proteases and amylases, used in detergent preparations, as the most significant industrial application of enzymes.
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Enzymes' use in detergents dates to 1988. Lipase, derived from the fungus Thermomyces lanuginosus, is effective at removing fat stains from clothes.
Most detergents contain several enzymes, such as proteases, amylases, cellulases and lipases, to enhance effectiveness and allow washing at lower temperatures.
Fungi are also used to keep clothing looking fresh.
Fungi are natural degraders of waste material, Prescott said. In forests, they break down leaf material by making enzymes called cellulases. "It happens that if you add cellulases to washing powders, it nibbles at the tiny cotton threads of cotton fabrics, and it kind of nibbles them off, and it gives the appearance of cotton looking newer than it perhaps actually is."
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In September, the fungus Aspergillus tubingensis was discovered in Pakistan. A team of 100 scientists reported that it could break down plastics such as polyester polyurethane, often used in refrigerator insulation, possibly in weeks rather than years, potentially making it a key player in the fight against the world's plastic waste problem.
Prescott believes the ultimate goal would be to create plastic-like materials from fungi -- that can then be broken down by fungi. It is not clear whether that might be possible, but "that's what makes it really exciting," he added.

Fungus in farming

Another way to reduce pollution is by adding enzymes to animal feed, helping animals break down nutrients such as phosphates, which farmers add to enhance animal bone health and growth.
One fungal enzyme, phytase, breaks down such difficult chemicals and is especially helpful for some phosphate-containing molecules that can't be digested by animals. When excreted, phosphates can get into waterways, where they cause bacterial growth. This also consumes oxygen in water, harming the ecosystem of the aquatic environment, said Prescott.
Landvik explained that the addition of phytase to release phosphates from feed and help animals absorb this essential nutrient also reduces costs for farmers and environmental pollution.
She believes enzymes in fungi are the key to making a number of industries more sustainable by replacing some industrial steps.
"And if you do have a mechanical or a chemical step in the industry that can often be replaced by an enzyme that can do the same. But with less impact on the environment."

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