Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

X-rays reveal how soil bacteria carry out surprising chemistry

05.03.2012
Discovery paves the way for new synthesis of antibiotics

Researchers working at the U.S. Department of Energy's (DOE) SLAC National Accelerator Laboratory have used powerful X-rays to help decipher how certain natural antibiotics defy a longstanding set of chemical rules – a mechanism that has baffled organic chemists for decades.

Their result, reported today in Nature, details how five carbon atoms and one oxygen atom in the structure of lasalocid, a natural antibiotic produced by bacteria in soil, can link into a six-membered ring through an energetically unfavorable chemical reaction. Unlocking this chemical pathway could enable scientists to synthesize many important chemicals currently found only in nature.

"Our study has a broad implication because the six-membered ring is a common structural feature found in hundreds of drug molecules produced by nature," said the study's principal investigator, Chu-Young Kim of the National University of Singapore. "We have actually analyzed the genes of six other organisms that produce similar drugs and we are now confident that the chemical mechanism we have uncovered applies to these other organisms as well."

According to "Baldwin's Rules for Ring Closure," which govern the way these rings form, this compound should contain a five-membered ring instead of the observed six-membered ring.

The solution to the molecular mystery depended in large part on a deeper understanding of the unique protein Lsd19, the catalyst that enables the formation of lasalocid's rings. To determine the protein's atomic structure, the researchers hit frozen crystals of Lsd19 with X-rays from SLAC's Stanford Synchrotron Radiation Lightsource and observed how the crystals diffracted the X-rays passing through. "You need atomic-level detail of the crystal's structure to understand what's really happening," said co-author Irimpan Mathews, a staff scientist at SLAC.

"The bugs have taught us a valuable chemistry lesson," Kim said. "With a new understanding of how nature synthesizes the six-membered rings, chemists may be able to develop novel methods that will enable us to produce these drugs with ease in the chemical laboratory. Alternatively, protein engineers may be able to use our results to develop a biofactory where these drugs are mass produced using a fermentation method. Either method will make more effective and more affordable drugs available to the public."

Kim's group has moved on to their next challenge: investigating how nature synthesizes the anti-cancer drug echinomycin. In the meantime, "The knowledge we have generated will help researchers in academia and industry to develop new methods for biological production of important polyether drugs," he said. "We are not talking about the distant future."

Additional authors included Kinya Hotta, Xi Chen, Hao Li and Kunchithapadam Swaminathan of the National University of Singapore, Robert S. Paton of Oxford University, Atsushi Minami and Hideaki Oikawa of Hokkaido University, Kenji Watanabe of the University of Shizuoka and Kendall N. Houk of the University of California Los Angeles. The research was supported by the Royal Commission for the Exhibition of 1851 and Fulbright-AstraZeneca Research Fellowship, the Japan Society for the Promotion of Science, the National Institutes of Health, the Ministry of Education, Culture, Sports, Science & Technology in Japan, and the National University of Singapore Life Sciences Institute Young Investigator Award. The Stanford Synchrotron Radiation Lightsource is supported by DOE's Office of Science and its Structural Molecular Biology program is also supported by the National Institutes of Health.

SLAC is a multi-program laboratory exploring frontier questions in photon science, astrophysics, particle physics and accelerator research. Located in Menlo Park, California, SLAC is operated by Stanford University for the U.S. Department of Energy Office of Science. To learn more, please visit http://www.slac.stanford.edu.

DOE's Office of Science is the single largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time. For more information, please visit http://www.science.energy.gov

Andy Freeberg | EurekAlert!
Further information:
http://www.science.energy.gov
http://www.slac.stanford.edu

More articles from Life Sciences:

nachricht How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>