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
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
28.03.2017 | Life Sciences
28.03.2017 | Information Technology
28.03.2017 | Physics and Astronomy