Nav: Home

What's in this plant? The best automated system for finding potential drugs

March 28, 2019

Researchers at the RIKEN Center for Sustainable Resource Science (CSRS) in Japan have developed a new computational mass-spectrometry system for identifying metabolomes--entire sets of metabolites for different living organisms. When the new method was tested on select tissues from 12 plants species, it was able to note over a thousand metabolites. Among them were dozens that had never been found before, including those with antibiotic and anti-cancer potential.

The common pain reliever aspirin (acetylsalicylic acid) was first made in the 19th century, and is famously derived from willow bark extract, a medicine that was described in clay tablets thousands of years ago. After a new method of synthesis was discovered, and after it had been used around the world for almost 70 years, scientists were finally able to understand how it works. This was a long historical process, and while plants remain an almost infinite resource for drug discovery and biotechnology, thousands of years is no longer an acceptable time frame.

Why does it take so long?

The biggest problem is that there are millions of plant species and each has its own metabolome--the set of all products of the plant's metabolism. Currently, we only know about 5% of all these natural products. Although mass spectrometry can identify plant metabolites, it only works for determining if a sample contains a given molecule. Searching for as-yet-unknown metabolites is another story.

Computational mass spectrometry is a growing research field that focuses on finding previously unknown metabolites and predicting their functions. The field has established metabolome databases and repositories, which facilitate global identification of human, plant, and microbiota metabolomes. Led by Hiroshi Tsugawa and Kazuki Saito, a team at CSRS has spent several years developing a system that can quickly identify large numbers of plant metabolites, including those that have not been identified before.

As Tsugawa explains, "while no software can comprehensively identify all the metabolites in a living organism, our program incorporates new techniques in computational mass spectrometry and provides 10 times the coverage of previous methods." In tests, while mass spectrometry-based methods only noted about one hundred metabolites, the team's new system was able to find more than one thousand.

The new computational technique relies on several new algorithms that compare the mass spectrometry outputs from plants that are labeled with carbon-13 with those that are not. The algorithms can predict the molecular formula of the metabolites and classify them by type. They can also predict the substructure of unknown metabolites, and based on similarities in structure, link them to known metabolites, which can help predict their functions.

Being able to find unknown metabolites is a key selling point for the new software. In particular, the system was able to characterize a class of antibiotics (benzoxazinoids) in rice and maize as well as a class with anti-inflammatory and antibacterial properties (glycoalkaloids) in the common onion, tomato, and potato. It was also able to identify two classes of anti-cancer metabolites, one (triterpene saponins) in soy beans and licorice, and the other (beta-carboline alkaloid) in a plant from the coffee family.

In addition to facilitating the screening of plant-specialized metabolomes, the new process will speed up the discovery of natural products that could be used in medicines, and also increase understanding of plant physiology in general.

As Tsugawa notes, use of this new method is not limited to plants. "I believe that computationally decoding metabolomic mass spectrometry data is linked to a deeper understanding of all metabolisms. Our next goal is to improve this methodology to facilitate global identification of human and microbiota metabolomes as well. Newly found metabolites can then be further investigated via genomics, transcriptomics, and proteomics."
-end-
This study was published March, 28 in Nature Methods.

Reference: Tsugawa et al. (2019) A cheminformatics approach to characterize metabolomes in stable isotope-labeled organisms. Nature Methods. doi: 10.1038/s41592-019-0358-2

RIKEN

Related Mass Spectrometry Articles:

Proximity of hospitals to mass shootings in US
Nontrauma center hospitals were the nearest hospitals to most of the mass shootings (five or more people injured or killed by a gun) that happened in the US in 2019.
Chemists use mass spectrometry tools to determine age of fingerprints
Chemists at Iowa State University may have solved a puzzle of forensic science: How do you determine the age of a fingerprint?
Keeping guns away from potential mass shooters
Researchers from Michigan State University measured the extent to which mass shootings are committed by domestic violence perpetrators, as well as identyifying how they illegally obtain guns, suggesting how firearm restrictions may prevent these tragedies.
Who is left behind in Mass Drug Administration?
Ensuring equity in the prevention of neglected tropical diseases (NTDs) is critical to reach NTD elimination goals as well as to inform Universal Health Coverage (UHC).
A mechanism capable of preserving muscle mass
By studying the young and aging muscles in mice, researchers from the Myology Research Center (Sorbonne Universite-Inserm) of the Institute of Myology identified a protein, CaVbeta1E that activates the factor GDF5.
Eyeballing a black hole's mass
There are no scales for weighing black holes. Yet astrophysicists from the Moscow Institute of Physics and Technology have devised a new way for indirectly measuring the mass of a black hole, while also confirming its existence.
Changes in gun purchases after mass shootings
For this analysis, researchers examined monthly data on US background checks for gun purchases and permits from November 1998 through April 2016, and they looked for purchasing trends after mass shootings during that time.
Study links perimenopause to accelerated fat mass gains, lean mass losses
A UCLA-led study confirms what women approaching menopause have long suspected: menopause does make fat go up.
Paleontology: Diversification after mass extinction
A team led by Ludwig-Maximilians-Universitaet in Munich paleontologist Adriana López-Arbarello has identified three hitherto unknown fossil fish species in the Swiss Alps, which provide new insights into the diversification of the genus Eosemionotus.
Mass spectrometry sheds new light on thallium poisoning cold case
In 1994, Chinese university student Zhu Ling began experiencing stomach pain, hair loss and partial paralysis.
More Mass Spectrometry News and Mass Spectrometry Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.