Featured Research

from universities, journals, and other organizations

X-rays reveal how soil bacteria carry out surprising chemistry

Date:
March 5, 2012
Source:
National University of Singapore
Summary:
Researchers have discovered how soil bacteria carry out surprising chemistry, defying a longstanding set of chemical rules and thus paving the way for new synthesis of polyether drugs.

This is a ribbon diagram of the protein Lsd19, which catalyzes the formation of six-membered rings in lasalocid.
Credit: Image by Kinya Hotta

Researchers from Singapore, Japan, the UK and USA have discovered how soil bacteria carry out surprising chemistry, defying a longstanding set of chemical rules and thus paving the way for new synthesis of polyether drugs.

Principal investigator, Chu-Young Kim, Assistant Professor at the Department of Biological Sciences of the National University of Singapore (NUS) Faculty of Science, and his group have made use of powerful X-rays to decipher how antibiotic-producing bacteria defy a longstanding set of chemical rules.

Their result, recently reported in Nature, details how a soil bacterium, Streptomyces lasaliensis, is able to convert an epoxide into a six-membered cyclic ether during synthesis of lasalocid, a natural polyether antibiotic. The fact that bacteria can perform such chemistry has puzzled chemists and biologists for decades because this type of chemical transformation is known to be kinetically unfavorable.

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

"Our study has broad implications because the six-membered cyclic ether is a common structural feature found in hundreds of drug molecules produced by nature," said Dr Kim. "We have analysed the genes of six other organisms that produce similar polyether drugs and we are now confident that the biosynthetic strategy we have uncovered is also used by those organisms."

The solution to the molecular mystery depended in large part on a deeper understanding of the unique enzyme Lsd19 that catalyses the formation of two cyclic ether moieties that are part of the lasalocid structure. To determine the protein's atomic structure, researchers hit frozen crystals of Lsd19 with X-rays at the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, and analysed how the crystals diffracted the X-rays. "You need atomic-level detail of the protein's structure to understand what's really happening," said co-author Irimpan Mathews, a staff scientist at SLAC.

Lessons from the bugs

"The bugs have taught us a valuable chemistry lesson," Dr Kim said.

"With a new understanding of how nature synthesises the six-membered rings, chemists may be able to develop new methods to produce polyether drugs with ease in the laboratory. Alternatively, protein engineers may be able to use our results to develop a biofactory, where polyether drugs are mass produced using fermentation. Either method will make more effective and more affordable drugs available to the public."

Next challenge: Elucidating how nature synthesises an anti-cancer compound

Dr Kim's group has moved on to their next challenge: investigating how nature synthesises echinomycin, an anti-cancer compound produced, again, by soil bacteria. "We still have much chemistry to learn from the bugs."

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 at Los Angeles.


Story Source:

The above story is based on materials provided by National University of Singapore. Note: Materials may be edited for content and length.


Journal Reference:

  1. Kinya Hotta, Xi Chen, Robert S. Paton, Atsushi Minami, Hao Li, Kunchithapadam Swaminathan, Irimpan I. Mathews, Kenji Watanabe, Hideaki Oikawa, Kendall N. Houk, Chu-Young Kim. Enzymatic catalysis of anti-Baldwin ring closure in polyether biosynthesis. Nature, 2012; DOI: 10.1038/nature10865

Cite This Page:

National University of Singapore. "X-rays reveal how soil bacteria carry out surprising chemistry." ScienceDaily. ScienceDaily, 5 March 2012. <www.sciencedaily.com/releases/2012/03/120305081247.htm>.
National University of Singapore. (2012, March 5). X-rays reveal how soil bacteria carry out surprising chemistry. ScienceDaily. Retrieved August 1, 2014 from www.sciencedaily.com/releases/2012/03/120305081247.htm
National University of Singapore. "X-rays reveal how soil bacteria carry out surprising chemistry." ScienceDaily. www.sciencedaily.com/releases/2012/03/120305081247.htm (accessed August 1, 2014).

Share This




More Matter & Energy News

Friday, August 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Britain Testing Driverless Cars on Roadways

Britain Testing Driverless Cars on Roadways

AP (July 30, 2014) British officials said on Wednesday that driverless cars will be tested on roads in as many as three cities in a trial program set to begin in January. Officials said the tests will last up to three years. (July 30) Video provided by AP
Powered by NewsLook.com
7 Ways to Use Toothpaste: Howdini Hacks

7 Ways to Use Toothpaste: Howdini Hacks

Howdini (July 30, 2014) Fresh breath and clean teeth are great, but have you ever thought, "my toothpaste could be doing more". Well, it can! Lots of things! Howdini has 7 new uses for this household staple. Video provided by Howdini
Powered by NewsLook.com
Amid Drought, UCLA Sees Only Water

Amid Drought, UCLA Sees Only Water

AP (July 30, 2014) A ruptured 93-year-old water main left the UCLA campus awash in 8 million gallons of water in the middle of California's worst drought in decades. (July 30) Video provided by AP
Powered by NewsLook.com
Smartphone Powered Paper Plane Debuts at Airshow

Smartphone Powered Paper Plane Debuts at Airshow

AP (July 30, 2014) Smartphone powered paper airplane that was popular on crowdfunding website KickStarter makes its debut at Wisconsin airshow (July 30) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins