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 Physics of bubbles could explain language patterns
25.07.2017 | University of Portsmouth

nachricht Obstructing the ‘inner eye’
07.07.2017 | Friedrich-Schiller-Universität Jena

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: Carbon Nanotubes Turn Electrical Current into Light-emitting Quasi-particles

Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers

Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...

Im Focus: Flexible proximity sensor creates smart surfaces

Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.

At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA mission surfs through waves in space to understand space weather

25.07.2017 | Physics and Astronomy

Strength of tectonic plates may explain shape of the Tibetan Plateau, study finds

25.07.2017 | Earth Sciences

The dense vessel network regulates formation of thrombocytes in the bone marrow

25.07.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>