An unusual chemical compound isolated from a mud-dwelling fungus found in a soil sample collected in Daejeon, South Korea, could lead to a new family of antitumor drugs.
Discovered by teams led by Jong Seog Ahn at the Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang, and Hiroyuki Osada at the RIKEN Advanced Science Institute, Wako, the compound prevents cancerous cells from forming mobile colonies—the point at which cancers become malignant and spread through the body1. The teams began collaborating after Yukihiro Asami from RIKEN joined KRIBB.
The researchers spotted the compound while searching extracts of the fungus for candidate drug compounds using a recently developed screen called a 3D epithelial culture system. To date, this kind of biological assay has rarely been used to search for natural products with novel bioactivity, says Ahn. It was during the 3D screen, which they spiked with cancerous cells, that the researchers realized that a compound produced by the fungus was inhibiting the cancer cells from clumping together to form colonies (Fig. 1). This type of screen is difficult using a conventional two-dimensional cell culture.
The researchers isolated the bioactive compound and named it fusarisetin A. They then investigated its structure using an array of chemical characterization techniques, including nuclear magnetic resonance (NMR) and x-ray crystallography. They showed that fusarisetin A was a previously undescribed compound. Being able to grow crystals of the compound for x-ray studies was a breakthrough, says Osada. “It is very important for exact structural elucidation to get crystal analysis,” he says.
Having established that fusarisetin A is a new compound, the researchers probed its bioactivity in more detail. They showed that it simply blocks colony formation rather than killing cancer cells. They then compared the compound to others known to inhibit this process, and showed that it works differently to other compounds capable of blocking clumping. This suggests to the researchers that it could offer a new way to treat tumors.
The team is already working to discover how fusarisetin A inhibits the clumping of cancerous cells by looking for its molecular target. “We have already got candidate target proteins,” Osada adds.
Fusarisetin A itself is not bioactive enough to become a drug. However, it may be possible to fine-tune the structure to improve its activity, from which new drugs could be developed. “If we can get higher biological activity derivatives [of fusarisetin A], it may be possible,” says Ahn.
Jang, J.-H., Asami, Y., Jang, J.-P., Kim, S.-O., Moon, D.O., Shin, K.-S., Hashizume, D., Muroi, M., Saito, T., Oh, H., Kim, B.-Y., Osada, H. & Ahn, J.-S. Fusarisetin A, an acinar morphogenesis inhibitor from a soil fungus, Fusarium sp. FN080326. Journal of the American Chemical Society 133, 6865–6867 (2011).
Modern genetic sequencing tools give clearer picture of how corals are related
17.08.2017 | University of Washington
The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
17.08.2017 | Physics and Astronomy
17.08.2017 | Materials Sciences
17.08.2017 | Materials Sciences