Alpha-amanitin is the poison of the death cap mushroom, Amanita phalloides. The Michigan State University plant biology research associate was looking for a big gene that makes a big enzyme that produces alpha-amanitin, since that’s how other fungi produce similar compounds. But after years of defeat, she and her team called in the big guns – new technology that sequences DNA about as fast as a death cap mushroom can kill.
The results: The discovery of remarkably small genes that produce the toxin – a unique pathway previously unknown in fungi.
The discovery is reported in today’s Proceedings of the National Academy of Sciences. It is work that not only solves a mystery of how some mushrooms make the toxin – but also sheds light on the underlying biochemical machinery. It might be possible one day to harness the mushroom genes to make novel chemicals that would be useful as new drugs.
“We think we have a factory that spits out lots of little sequences to make chemicals in Amanita mushrooms,” said Jonathan Walton, MSU plant biology professor who leads Hallen’s team. “Our work indicates that these mushrooms have evolved a mechanism to make dozens or even hundreds of new, previously unknown chemicals, besides the toxins that we know about.”
Of the thousands of species of mushrooms, only about 30 produce alpha-amanitin. Most of them look much like their edible cousins. But poisonous mushrooms are powerful in folklore and in history. In 54 A.D., Emperor Tiberius Claudius was fed a death cap mushroom by his wife Agrippina to put her son Nero on the throne of Rome.
Alpha-amanitin kills people by inhibiting an enzyme necessary for expression of most genes. Without the ability to synthesize new proteins, cells quickly grind to a halt. The intestinal tract and the liver are the hardest hit as they come into first contact with the toxin. By the time symptoms show up, a liver transplant is often the only hope.
Hallen, a mycologist, gathers mushrooms in the Michigan woods and often is called upon to help identify mushroom species for veterinarians, parents of small children and local hospitals – often in a desperate race to beat alpha-amanitin’s effects.
Walton’s lab works to understand the biochemical pathways by which natural products are synthesized in fungi. Fungal natural products that benefit human health include penicillin and the immunosuppressant drug cyclosporin. Studying their biosynthesis could lead to the discovery and development of new medicines.
To find the elusive gene for alpha-amanitin, they used what they term “brute force” – a new machine at MSU that can sequence immense quantities of DNA quickly. The 454 LifeSciences pyrosequencer generates 100 Mb DNA sequence in one overnight run - twice the size of a fungal genome. Traditional sequencing methods require months to yield the same quantities. What they found was a gene that encodes the toxin directly – with no need to first synthesize an enzyme that in turn would make the toxin.
“The RNA goes in, and out comes the backbone of the toxin,” Hallen said. After its initial synthesis, the toxin is then modified in several ways by the mushroom to make it exceptionally poisonous.
Walton said the discovery poses some interesting evolutionary questions. For example, why do only some mushrooms produce this toxin" And how did a handful of other, unrelated mushrooms evolve the same trait" Finding the genes points to how the trait could appear in one mushroom, but not how it evolved in mushrooms that aren’t related to Amanita.
Hallen and Walton also see the doors opening to a diagnostic test that could use DNA to determine if a mushroom is toxic or not. Identifying a mushroom by shape and color alone is often impossible if the mushroom has been cooked or partially digested, yet rapid and accurate identification in an emergency room situation is critical.
Jonathan Walton | EurekAlert!
Microbe hunters discover long-sought-after iron-munching microbe
24.10.2016 | Max-Planck-Institut für marine Mikrobiologie
Seeking balanced networks: how neurons adjust their proteins during homeostatic scaling.
24.10.2016 | Max-Planck-Institut für Hirnforschung
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
24.10.2016 | Life Sciences
21.10.2016 | Health and Medicine
21.10.2016 | Information Technology