MIT researchers have discovered a way to manipulate the chemistry taking place in the tiny periwinkle plant to produce novel compounds that could have pharmacological benefits.
"Plants are really nature's best chemists," says Sarah O'Connor, the Latham Family Career Development Assistant Professor of Chemistry and co-author of a paper on the work in the Journal of the American Chemical Society.
O'Connor and chemistry graduate student Elizabeth McCoy decided to explore the periwinkle plant in part because it is the only plant that produces vinblastine, a drug widely used to treat cancers such as Hodgkin's lymphoma.
The biochemical pathway that produces vinblastine and other alkaloid compounds is long and complicated, usually requiring at least 10 enzymatic steps, which occur in different parts of the periwinkle plant (also known as Catharanthus roseus).
O'Connor and McCoy essentially tricked the plants into producing new compounds by feeding them slightly altered versions of the normal starting materials (tryptamines) for alkaloid synthesis.
"You can make a great number of modifications of simple starting materials, and the plants incorporate those starting materials into the biosynthetic pathway," said O'Connor.
Alkaloids are believed to have a protective function for plants because they are toxic to bacteria and herbivores who try to eat the plants. This theory is bolstered by the fact that the reaction products move closer to the plant surface as they move through the biosynthetic pathway, said McCoy.
Vinblastine, which has been used as a cancer drug since the 1960s, is very difficult to isolate from the periwinkle plant because it is produced in minute quantities (the yield is about 0.002 percent of the plant's weight). However, it would be even more difficult (and expensive) to synthesize vinblastine in the laboratory.
"It's a beautiful and elegant synthesis, but it's not cost-effective, so industry does not currently use synthesis to make vinblastine," said O'Connor.
Other researchers are now running clinical trials for artificial analogues of vinblastine, so it could be beneficial if periwinkle plants could be induced to synthesize those same compounds or new compounds that might be even more effective.
Because it is easier to make modifications to the starting materials than the end product, the researchers' method could produce a diverse array of alkaloids to test for potential drug activity. "You can only make a limited number of modifications to natural products that are already synthesized," O'Connor said.
In their recent paper, the researchers describe 18 new products, but there are many more possibilities. "There's no end to what you could do to modify the starting materials," said McCoy.
Scientists often engineer bacteria and yeast to produce desired compounds, such as antibiotics, but few have tried it with plants, because their biochemistry is so complex.
"Plants are the hardest to work with, so people have avoided looking at plant biosynthetic pathways," O'Connor said.
The research is funded by the Smith Family Medical Foundation, 3M, the Beckman Foundation, the American Cancer Society and the American Chemical Society.
--Written by Anne Trafton, MIT News Office--
Elizabeth A. Thomson | MIT News Office
Don't Give the Slightest Chance to Toxic Elements in Medicinal Products
23.03.2018 | Physikalisch-Technische Bundesanstalt (PTB)
North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich
Satellites in near-Earth orbit are at risk due to the steady increase in space debris. But their mission in the areas of telecommunications, navigation or weather forecasts is essential for society. Fraunhofer FHR therefore develops radar-based systems which allow the detection, tracking and cataloging of even the smallest particles of debris. Satellite operators who have access to our data are in a better position to plan evasive maneuvers and prevent destructive collisions. From April, 25-29 2018, Fraunhofer FHR and its partners will exhibit the complementary radar systems TIRA and GESTRA as well as the latest radar techniques for space observation across three stands at the ILA Berlin.
The "traffic situation" in space is very tense: the Earth is currently being orbited not only by countless satellites but also by a large volume of space...
An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.
The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
23.03.2018 | Event News
19.03.2018 | Event News
16.03.2018 | Event News
23.03.2018 | Materials Sciences
23.03.2018 | Agricultural and Forestry Science
23.03.2018 | Physics and Astronomy