Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Innovative study finds way to ’bio-synthesize’ an anti-cancer compound

10.05.2005


Microbe in sea squirts key to process

In a project that could have far-reaching implications for natural-product drug development, scientists have shown how a microbe that lives inside sea squirts could be used to biosynthesize a chemical compound that may help fight cancer. The photosynthetic microbe, Prochloron didemni, lives as an endosymbiont inside the sea squirt Lissoclinum patella. So far, scientists have not been able to culture the microbe anywhere else.

Ground-up extracts of that sea squirt have been shown to contain patellamides, small peptides that appear useful in treating some cancers. Until this study, scientists had suspected – but had not proven – that Prochloron microbes produce patellamides.



The research paper, published online this week in the Proceedings of the National Academy of Sciences (PNAS), demonstrates that Prochloron didemni produces two patellamide compounds (A and C) and pinpoints the gene pathways that are used in that chemical biosynthesis.

"Coral reefs and other ocean environments are like rainforests – full of natural chemicals to potentially treat human disease," says Eric W. Schmidt, Ph.D., assistant professor of medicinal chemistry at the University of Utah’s College of Pharmacy. "Unfortunately, it’s difficult to supply pharmaceuticals from these delicate environments. We have solved this by finding specific genes for the synthesis of chemicals using laboratory bacteria."

Schmidt had isolated and prepared the DNA of the microbe samples collected from sea squirts in the seabed near the Republic of Palau in Micronesia. Jacques Ravel, Ph.D., and other scientists at The Institute for Genomic Research (TIGR) in Rockville, MD, then sequenced the Prochloron genome. Working with Schmidt, they found the chemical pathways in the microbe’s gene sequence that are responsible for producing patellamide A and C.

Ravel, who led TIGR’s role in the project, says: "For the first time, we have demonstrated the bacterial origin of a natural product from tunicates, an important source of marine drug candidates." He added that the study "demonstrates how genomics can assist natural products chemistry and work towards sustainable production of important marine drug candidates from microbes. This process can speed up the time it takes for a drug to go from lead compound to actual drugs."

By proving that the patellamide compounds are made by the microbes inside sea squirts, scientists say, the study shows it would be possible to produce sufficient quantities of patellamides through biosynthesis without having to destroy a large numbers of sea squirts in the process. The study was funded as part of a National Science Foundation (NSF) grant in the Emerging Frontiers program (Microbial Genome Sequencing).

Because patellamides are small cyclic peptides (consisting of eight amino acids), scientists had at first thought that – as in the case of many other small cyclic peptides – the biosynthetic mechanism involved a "non-ribosomal peptide synthetase," a large multimodular enzyme that incorporates amino acids residue into a peptide.

When scientists did not find such a chemical system related to patellamides in the microbe’s draft genome sequence, they examined alternative biosynthetic mechanisms. Because it is a peptide, a ribosomal mechanism was an obvious possibility.

In a collaboration with Schmidt, TIGR scientists looked for every combination of eight amino acids constituting the cyclic patellamides in the draft genome. Ravel’s group found the sequence for Patellamide A, and – after further examination – Schmidt’s group found the Patellamide C sequence adjacent to the patellamide A sequence in the same pre-peptides. After the gene cluster was annotated, Schmidt used the TIGR information to develop the likely mechanism for the biosynthesis of the patellamides and he demonstrated how the biosynthesis could be accomplished.

The Prochloron genome project – which also involves collaborator Margo Haygood at the Scripps Institution of Oceanography at the University of California in San Diego – is still under way, with scientists exploring more aspects of the microbe’s DNA sequence.

TIGR’s Jonathan Eisen, an evolutionary biologist, says the PNAS study also helps explain how a specific microbe contributes to the biology of its host organism: "This study is particularly important since it helps reveal how a bacterial symbiont plays a role in the biology of a tunicate, which as a representative of the chordates, is not so far away from humans in the tree of life."

Eisen says the study "shows yet another way that microorganisms contribute to the biology of animals. Most animals, including humans, simply cannot survive without the functions and activities provided to them by mutualistic microorganisms that live either inside or in association with them."

Phil Sahm | EurekAlert!
Further information:
http://www.utah.edu

More articles from Studies and Analyses:

nachricht Reusable carbon nanotubes could be the water filter of the future, says RIT study
30.03.2017 | Rochester Institute of Technology

nachricht Pan-European study on “Smart Engineering”
30.03.2017 | IPH - Institut für Integrierte Produktion Hannover gGmbH

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

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...

Im Focus: Giant Magnetic Fields in the Universe

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...

Im Focus: Tracing down linear ubiquitination

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...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

'On-off switch' brings researchers a step closer to potential HIV vaccine

30.03.2017 | Health and Medicine

Penn studies find promise for innovations in liquid biopsies

30.03.2017 | Health and Medicine

An LED-based device for imaging radiation induced skin damage

30.03.2017 | Medical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>